Immunological and Formulation Design Considerations for Subunit Vaccines

  • Mark J. Newman
  • Michael F. Powell
Part of the Pharmaceutical Biotechnology book series (PBIO, volume 6)

Abstract

Vaccination represents the most successful attempt yet to protect humans and domestic animals from infectious diseases. Most vaccines operate by limiting infections, not necessarily by preventing them; it is the host immune system that mediates control and ultimate clearance of the infectious agent. Many of the most widely used vaccines developed for use in humans are based on live replicating organisms that have been attenuated. Vaccination with these agents results in a limited infection, but measurable disease pathogenesis is usually avoided and recovery is complete. The resultant immune responses are protective against the fully virulent pathogens and long-term immunological memory is induced. Today, attenuated vaccines are still used and efforts to develop the next generation are active.

Keywords

Major Histocompatibility Complex Respiratory Syncytial Virus Major Histocompatibility Complex Class Subunit Vaccine Intracellular Bacterium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Acres, R. B., Hareuveni, M, Balloul, J.-M., and Kieny, M.-P., 1993, Vaccinia virus MUC1 immunization of mice: Immune response and protection against the growth of murine tumors bearing the MUC1 antigen, J. Immunother. 14:136–143.CrossRefGoogle Scholar
  2. Alfonso, L. C. C., Sharton, T. M., Vierira, L. Q., Wysocka, M., Thinchieri, G., and Scott, P., 1994, The adjuvant effect of interleukin-12 in a vaccine against Leishmania major, Science 263:235–237.CrossRefGoogle Scholar
  3. Alving, C. R., Richards, R. L., and Moss, J., 1986, Effectiveness of liposomes as potential carriers of vaccines: Applications to cholera toxin and human malarial sporozoite antigen, Vaccine 4:166–172.PubMedCrossRefGoogle Scholar
  4. Alwan, W. H., Record, F. M., and Openshaw, P.J. M., 1993, Phenotypic and functional characterization of T cell Unes specific for individual respiratory syncytial virus proteins, J. Immunol. 150:5211–5218.PubMedGoogle Scholar
  5. Anderson, K. P., Lucas, C., Hanson, C. V., Londe, H. F., Izu, A., Gregory, T., Ammann, A., Berman, P. W., and Eichberg, J. W., 1989, Effect of dose and immunization schedule on immune response of baboons to recombinant glycoprotein 120 of HIV-1, J. Infect. Dis. 160:960–969.PubMedCrossRefGoogle Scholar
  6. Anderson, M. S., and Miler, J., 1992, Invariant chain can function as a chaperon protein for class II major histocompatibility complex molecules, Proc. Natl. Acad. Sci. USA 89:2282–2286.PubMedCrossRefGoogle Scholar
  7. Anderson, P., 1983, Antibody responses to H. influenzae type b and diphtheria toxin induced by conjugates of Oligosaccharides of the type b capsule with the nontoxic protein CRM197, Infect. Immun. 39:233–238.PubMedGoogle Scholar
  8. Anderson, P., and Heron, I., 1993, Specificity of a protective immune response against Mycobacterium tuberculosis, Infect. Immun. 61:844–851.Google Scholar
  9. Anderson, P., Pichichero, M. E., and Insel, R. A., 1985, Immunization of 2-month-old infants with protein-coupled Oligosaccharides derived from capsule of H. influenzae type b, J. Pediatr. 107:346–351.PubMedCrossRefGoogle Scholar
  10. Anderson, P., Askgaard, D., Ljungqvist, L., Bentzon, M. W., and Heron, I., 1991, T-cell proliferative response to antigens secreted from Mycobacterium tuberculosis, Infect. Immun. 59:1558–1563.Google Scholar
  11. Anderson, P., Askgaard, D., Gottschau, A., Bennedsen, J., Nagai, S., and Heron, I., 1992, Identification of immunodominant antigens during infection with Mycobacterium tuberculosis, Scand. J. Immunol. 36:823–831.CrossRefGoogle Scholar
  12. Andrade, J. D., Hlady, V., Wei, A.-P., Ho, C.-H., Lea, A. S., Jeon, S. I., Lin, Y. S., and Stroup, E., 1992, Proteins at interfaces: Principles, multivariate aspects, protein resistant surfaces, and direct imaging and manipulation of adsorbed proteins, Clin. Mater. 11:67–70.CrossRefGoogle Scholar
  13. Aprile, M. A., and Wardlaw, A. C., 1966, Aluminum compounds as adjuvants for vaccines and toxoids in man: A review, Can. J. Public Health 57:343–360.PubMedGoogle Scholar
  14. Barnd, D. L., Lan, M. S., Metzgar, R. S., and Finn, O. J., 1989, Specific, major histocompatibility complex-unrestricted recognition of tumor-associated mucins by human cytotoxic T cells, Proc. Natl. Acad. Sci. USA 86:7159–7164.PubMedCrossRefGoogle Scholar
  15. Barnes, P. F., Abrams, J. S., Lu, S. Z., Sieling, P. A., Rea, T. H., and Modlin, R. L., 1993, Patterns of cytokine production by mycobacterium-reactive human T-cell clones, Infect. Immun. 61:197–203.PubMedGoogle Scholar
  16. Belshe, R. B., Clements, M. L., Dolin, R., Graham, B. S., McElrath, J., Gorse, G. J., Schwartz, D., Keefer, M. C., Wright, P., Corey, L., Bolognesi, D. M., Matthews, T. J., Stablein, D. M., O’Brien, F. S., Eibl, M., Dorner, F., Koff, W., and the NIH NIAID AIDS VEG., 1993, Safety and immunogenicity of a fully glycosylated recombinant gp160 human immunodeficiency virus type 1 vaccine in subjects at low risk of infection, J. Infect. Dis. 168:1387–1395.PubMedCrossRefGoogle Scholar
  17. Bennett, B., Check, I. J., Olsen, M. R., and Hunter, R. L., 1992, A comparison of commercially available adjuvants for use in research, J. Immunol. Methods 153:31–40.PubMedCrossRefGoogle Scholar
  18. Bennett, K., Levine, T., Ellis, J. S., Peanasky, R. J., Samloff, I. M., Kay, J., and Chain, B. M., 1992, Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E, Eur. J. Immunol. 22:1519–1524.PubMedCrossRefGoogle Scholar
  19. Berek, C., Berger, A., and Apel, M., 1991, Maturation of the immune response in germinal centers, Cell 67:1121–1129.PubMedCrossRefGoogle Scholar
  20. Berman, P. W., Gregory, T. J., Riddle, L., Nakamura, G. R., Champe, M. A., Porter, J. P., Wurm, F. M., Hershberg, R. D., Cobb, E. K., and Eichberg, J. W., 1990, Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant gp120 but not gp160, Nature 345:622–625.PubMedCrossRefGoogle Scholar
  21. Berman, P. W, Matthews, T., Eastman, D., Nakamura, G., Murthy, K., and Schwartz, D., 1993, Comparison of the immune response to recombinant gp120 in man and chimpanzees, IX International Conference on AIDS, Berlin, Germany, Abstract PO-B27-2135.Google Scholar
  22. Beverly, P. C. L., 1990, Is T cell memory maintained by cross-reactive stimulation? Immunol. Today 11:203–205.CrossRefGoogle Scholar
  23. Beverly, P. C. L., 1992, Functional analysis of human T cell subsets defined by CD45 isoform expression, Semin. Immunol. 4:35–41.Google Scholar
  24. Boon, W. H., Liano, D., and Abbas, A. K., 1988, Heterogeneity of helper/inducer T lymphocytes. II. Effects of interleukin 4-and interleukin 2-producing T cell clones on resting B lymphocytes, J. Exp. Med. 167:1352–1363.Google Scholar
  25. Boon, W. H., Wallis, R. S., and Chervenak, K. A., 1991, Human mycobacterium tuberculosis-reactive CD4+ T-cell clones: Heterogeneity in antigen recognition. Cytokine production and cytotoxicity for mononuclear phagocytes, Infect. Immun. 59:2737–2743.Google Scholar
  26. Braciale, T. J., Morrison, L. A., Sweetser, M. T., Sambrook, J., Gething, M.-J., and Braciale, V. L., 1987, Antigen presentation pathways to class I and class II MHC-restricted T lymphocytes, Immunol. Rev. 98:95–114.PubMedCrossRefGoogle Scholar
  27. Bradley, L. M., Duncan, D. D., Tonkonogy, S., and Swain, S. L., 1991, Characterization of antigen-specific CD4+ effector T cells in vivo: Immunization results in a transient population of Mel-14− CD45RB− helper cells that secrete interleukin-2 (IL-2), IL-3, IL-4 and interferon-γ, J. Exp. Med. 174:547–559.PubMedCrossRefGoogle Scholar
  28. Brewster, M. E., Hora, M. S., Simpkins, J. W., and Bodor, N., 1991, Use of 2-hydroxypropyl-beta-cyclodextrin as a solubilizing and stabilizing excipient for protein drugs, Pharm. Res. 8:792–795.PubMedCrossRefGoogle Scholar
  29. Brown, F., Dougan, G., Hoey, E. M., Martin, S. J., Rima, B. K., and Trudgen, A., 1993, Vaccine Design, Wiley, New York.Google Scholar
  30. Brown, M. G., Driscoll, J., and Monaco, J. J., 1991, Structural and serological similarity of MHC-linked LMP and proteosome (multicatalytic proteinase) complexes, Nature 353:335–357.CrossRefGoogle Scholar
  31. Bruguera, M., Cremades, M., Salinas, R., Costa, J., Grau, M., and Sans, J., 1992, Impaired response to recombinant hepatitis B vaccine in HIV-infected persons, J. Clin. Gastroenterol. 14:27–30.PubMedCrossRefGoogle Scholar
  32. Bu, D., Domenech, N., Lewis, J., Taylor-Papadimitriou, J., and Finn, O. J., 1993, Recombinant vaccinia mucin vector: In vitro analysis of expression of tumor-associated epitopes for antibody and human cytotoxic T-cell recognition, J. Immunother. 14:127–135.CrossRefGoogle Scholar
  33. Butterfield, K., Fathman, C. G., and Budd, R. C., 1989, A subset of memory CD4+ helper T-lymphocytes identified by expression of Pgp-1, J. Immunol. 169:1461–1466.Google Scholar
  34. Bystryn, J.-C., Ferrone, S., and Livingston, P., (eds.), 1993, Specific Immunotherapy of Cancer with Vaccines, Vol. 690, New York Academy of Sciences, New York.Google Scholar
  35. Cabasso, V. J., Louie, B. L., and Dobkin, M. B., 1978, Antibody levels following W138 rabies vaccine, Dev. Biol. Stand. 40:231–235.PubMedGoogle Scholar
  36. Callahan, P. M., Shorter, A. L., and Hem, S. L., 1991, The importance of surface charge in the optimization of antigen-adjuvant interactions, Pharm. Res. 8:851–858.PubMedCrossRefGoogle Scholar
  37. Carpenter, J. F., Arakawa, T., and Crowe, J. H., 1990, Interactions of stabilizing additives with proteins during freeze-thawing and freeze-drying, Dev. Biol. Stand. 74:225–238.Google Scholar
  38. Cheever, M. A., Chen, W., Nelson, H., Greenberg, P. D., Lee, V. K., Crossland, K. D., and Peace, D. J., 1990, T cell immunity to the oncogenic form of ras protein can be induced by immunization with synthetic peptides, in: Cellular Immunity and Immunotherapy of Cancer (M. T. Lotze and O. J. Finn, eds.), Wiley-Liss, New York, pp. 295–302.Google Scholar
  39. Chen, T., 1992, Formulation concerns of protein drugs, Drug Dev. Ind. Pharm. 18:1311–1354.CrossRefGoogle Scholar
  40. Cher, D. J., and Mosmann, T. R., 1987, Two types of murine helper cell clones: 2. Delayed-type hypersensitivity is mediated by TH1 clones, J. Immunol. 138:3688–3694.PubMedGoogle Scholar
  41. Cleland, J. L., Powell, M. F., and Shire, S., 1993, The development of stable protein formulations: A close look at protein aggregation, deamidation and oxidation, Crit. Rev. Ther. Drug Carrier Syst. 10:307–377.PubMedGoogle Scholar
  42. Cleland, J. L., Powell, M. F., Lim, A., Barrón, L., Berman, P. W., Eastman, D. J., Nunberg, J. H., Wrin, T., and Vennari, J. C., 1994, Development of a single shot subunit vaccine for HIV-1, AIDS Res. Hum. Retroviruses 10:521–526.CrossRefGoogle Scholar
  43. Clerici, M., and Shearer, G. M., 1993, A TH1-TH2 switch is a critical step in the etiology of HIV infection, Immunol. Today 14:107–111.PubMedCrossRefGoogle Scholar
  44. Coffman, R. L., Seymour, B. W., Lebman, D. A., Hiraki, D. D., Christiansen, J. A., Shrader, B., Cherwinski, H. M., Savelkoul, H. F. J., Finkelman, F. D., Bond, M. W., and Mosmann, T. R., 1988, The role of helper T cell products in mouse B cell differentiation and isotype regulation, Immunol. Rev. 102:5–28.PubMedCrossRefGoogle Scholar
  45. Cohen, S., Bernstein, H., Hewes, C., Chow, M., and Langer, R., 1991, The pharmacokinetics of, and humoral responses to, antigen delivered by microencapsulated liposomes, Proc. Natl. Acad. Sci. USA 88:10440–10444.PubMedCrossRefGoogle Scholar
  46. Colditz, G. A., Brewer, T. F., Berkey, C. S., Wilson, M. E., Burdick, E., Fineberg, H. V., and Mosteller, F., 1994, Efficacy of BCG vaccine in the prevention of tuberculosis: Meta-analysis of the published literature, J. Am. Med. Assoc. 271:698–702.CrossRefGoogle Scholar
  47. Collins, D. S., Unanue, E. R., and Harding, C. V., 1991, Reduction of disulfide bonds within lysosomes is a key step in antigen processing, J. Immunol. 147:4054–4059.PubMedGoogle Scholar
  48. Constant, S. L., and Wilson, R. A., 1992, In vivo responses in the draining lymph nodes of mice exposed to Schistosoma mansoni: Preferential proliferation of T cells is central to the induction of protective immunity, Cell. Immunol. 139:145–161.PubMedCrossRefGoogle Scholar
  49. Cox, J., and Coulter, A., 1992, Advances in adjuvant technology and application, in: Animal Parasite Control Utilizing Biotechnology (W. K. Yong, ed.), CRC Press, Boca Raton, pp. 49–111.Google Scholar
  50. Craven, D. E., Awdeh, R., Kunches, L. M., Yunis, E. J., Dienstag, J. L., Werner, B. G., Polk, B. F., Syndman, D. R., Platt, R., and Crumpacker, C. S., 1986, Nonresponsiveness to hepatitis B vaccine in health care workers. Results of revaccination and genetic typings, Ann. Intern. Med. 105:356–360.PubMedGoogle Scholar
  51. Czerkinsky, C., Russell, M. W., Lycke, N., Lindbad, M., and Holmgren, J., 1989, Oral administration of a streptococcal antigen coupled to cholera toxin B subunit evokes strong antibody responses in salivary glands and extramucosal tissues, Infect. Immun. 57:1072–1077.PubMedGoogle Scholar
  52. Daugelat, S., Guile, H., Schoel, B., and Kaufmann, S. H. E., 1992, Secreted antigens of Mycobacterium tuberculosis — Characterization with T-lymphocytes from patients and contacts after two-dimensional separation, J. Infect. Dis. 166:186–190.PubMedCrossRefGoogle Scholar
  53. Degen, E., and Williams, D. B., 1991, Participation of a novel 88 KD protein in the biogenesis of murine class I histocompatibility molecules, J. Cell Biol. 112:1099–1115.PubMedCrossRefGoogle Scholar
  54. Del Prete, G. F., De Carli, M., Mastromauro, C., Biagiotti, R., Macchia, D., Falagiani, P., Ricci, M., and Romagnani, S., 1991, Purified protein derivative of Mycobacterium tuberculosis and excretory-secretory antigen(s) of Toxocara canis expand in vitro human T cells with stable and opposite (type 1 T helper or type 2 T helper) profile of cytokine production, J. Clin. Invest. 88:346–350.PubMedCrossRefGoogle Scholar
  55. Del Prete, G. F., De Carli, M., Almerigogna, F., Grazia-Giudizi, M., Biagiotti, R., and Romagnani, S., 1993, Human IL-10 is produced by both type 1 helper (TH1) and type 2 helper (TH2) T cell clones and inhibits their antigen-specific proliferation and cytokine production, J. Immunol. 150:353–360.PubMedGoogle Scholar
  56. Del Prete, G. F., Maggi, E., and Romagnani, S., 1994, Biology of disease: Human Thl and Th2 cells: Functional properties, mechanisms of regulation, and role in disease, Lab. Invest. 70:299–306.PubMedGoogle Scholar
  57. Dessein, A. J., Couissinier, P., Demeure, C., Rihet, P., Kohlstaedt, S., Carneiro-Carvalho, D., Ouattara, M., Goudot-Crozel, V., Dessein, H., Bourgois, A., Carvallo, E. M, and Prata, A., 1992, Environmental, genetic and immunological factors in human resistance to Schistosoma mansoni, Immunol. Invest. 21:423–453.PubMedCrossRefGoogle Scholar
  58. Deveikis, A., Kim, K. S., and Ward, J. I., 1988, Prevention of H. influenzae type b in infant rats by human antibody induced by the capsular Polysaccharides and polysaccharide-conjugate vaccines, Vaccines 6:14–18.CrossRefGoogle Scholar
  59. De Waal-Malefyt, R., Haanen, J., Spits, H., Roncarolo, M.-G., Velde, A., Figdor, C., Johnson, K., Kastelein, R., Yssel, H., and De Vries, J., 1991, Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigenspecific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via down regulation of class II major histocompatibility complex expression, J. Exp. Med. 174:915–924.PubMedCrossRefGoogle Scholar
  60. Disis, M. L., Calenoff, E., McLaughlin, G., Murphy, A. E., Chen, W., Groner, B., Jeschke, M., Lydon, N., McGlynn, E., Livingston, R. B., Moe, R., and Cheever, M. A., 1994, Existent T-cell and antibody immunity to HER-2/neu protein in patients with breast cancer, Cancer Res. 54:16–20.PubMedGoogle Scholar
  61. Doherty, P. C., 1993, Virus infections in mice with targeted gene disruptions, Curr. Opin. Immunol. 5:479–483.PubMedCrossRefGoogle Scholar
  62. Doherty, P. C., Allan, W., Eichelberger, M., and Carding, S. R., 1992, Roles of αβ and γδ T cell subsets in viral immunity, Annu. Rev. Immunol. 10:123–151.PubMedCrossRefGoogle Scholar
  63. Donbrow, M., Azaz, E., and Pillersdorf, A., 1978, Autoxidation of polysorbates, J. Pharm. Sci. 67:1676–1681.PubMedCrossRefGoogle Scholar
  64. Dryden, M. W., and Blakemore, J. C., 1989, A review of flea allergy dermatitis in the dog and cat, Compan. Animal Pract. 19:10–17.Google Scholar
  65. Dunne, D. W., Butterworth, A. E., Fulford, A. J. C., Kariuki, H. C., Langley, J. G., Ouma, J. H., Capron, A., Pierce, R. J., and Sturrock, R. F., 1992, Immunity after treatment of human Schistosomiasis: Association between IgE antibodies to adult worm antigens and resistance to reinfection, Eur. J. Immunol. 22:1483–1494.PubMedCrossRefGoogle Scholar
  66. Eddleston, A., 1990, Modern vaccines. Hepatitis, Lancet 1:1142–1145.CrossRefGoogle Scholar
  67. Edelman, R., and Tacket, C. O., 1990, Adjuvants, Int. Rev. Immunol. 7:51–66.PubMedCrossRefGoogle Scholar
  68. Eichelberger, M., Allan, W., Zijlstra, M., Jaenisch, R., and Doherty, P. C., 1991, Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8+ T cells, J. Exp. Med. 174:875–880.PubMedCrossRefGoogle Scholar
  69. Einhorn, M. S., Weinberg, G. A., Anderson, E. L., Granoff, P. D., and Granoff, D. M., 1986, Immunogenicity in infants of H. influenzae type b Polysaccharide in a conjugate vaccine with Neisseria meningitidis outer-membrane protein, Lancet 2:299–302.PubMedCrossRefGoogle Scholar
  70. Eisen, H. N., and Siskind, G. W., 1964, Variations in affinities of antibodies during the immune response, Biochemistry 3:400–996.CrossRefGoogle Scholar
  71. Eldridge, J. H., Staas, J. K., Meulbroek, J. A., McGhee, J. R., Rice, T. R., and Gilley, R. M., 1991, Biodegradable microspheres as a vaccine delivery system, Mol. Immunol. 28:287–294.PubMedCrossRefGoogle Scholar
  72. Elson, C. O., and Ealding, W., 1984, Cholera toxin feeding did not induce oral tolerance in mice or abrogated oral tolerance to an unrelated oral antigen, J. Immunol. 133:2892–2897.PubMedGoogle Scholar
  73. Emini, E. A., Ellis, R. W., Miller, W. J., McAleer, W. J., Scolnick, E. M., and Gerety, R. J., 1986, Production and immunological analysis of recombinant hepatitis B virus vaccine, J. Infect. 13(A):31–38.Google Scholar
  74. Epstein, S. L., Misplon, J. A., Lawson, C. M., Subbarao, E. K., Connors, M., and Murphy, B. R., 1993, β2-microglobulin-deficient mice can be protected against influenza A infection by vaccination with vaccinia-influenza recombinants expressing hemagglutinin and neuraminidase, J. Immunol. 150:5484–5493.PubMedGoogle Scholar
  75. Ertiirk, M., Wellcn, M. J., Phillpotts, R. J., and Jennings, R., 1989, Protection and serum antibody responses in guinea pigs and mice immunized with HSV-1 antigen preparations obtained with different detergents, Vaccine 7:431–436.CrossRefGoogle Scholar
  76. Fadda, G., Maida, A., Masia, C., Obino, G., Romano, G., and Spano, E., 1987, Efficacy of hepatitis B immunization with reduced intradermal doses, Eur. J. Epidemiol. 3:176–189.PubMedCrossRefGoogle Scholar
  77. Falk, K., Rotzschke, O., and Rammensee, H.-G., 1990, Cellular peptide composition governed by major histocompatibility complex class I molecules, Nature 348:248–251.PubMedCrossRefGoogle Scholar
  78. Falk, K., Rotzschke, O., Stevanovic, S., Jung, G., and Rammensee, H. G., 1991, Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules, Nature 351:290–295.PubMedCrossRefGoogle Scholar
  79. Feldman, H. A., 1962, Protective value of inactivated measle vaccine, Am. J. Dis. Child. 103:423–424.PubMedGoogle Scholar
  80. Fenton, R. G., Taub, D. D., Kwak, L. W., Smith, M. R., and Longo, D. L., 1993, Cytotoxic T-cell response and in vivo protection against tumor cells harboring activated ras proto-oncogenes, J. Natl. Cancer Inst. 85:1294–1302.PubMedCrossRefGoogle Scholar
  81. Flynn, J. L., Goldstein, M. M, Triebold, K. J., Koller, B., and Bloom, B. R., 1992, Major histocompatibility complex class I-restricted T cells are required for resistance to Mycobacterium tuberculosis infection, Proc. Natl. Acad. Sci. USA 89:12013–12017.PubMedCrossRefGoogle Scholar
  82. Fulginiti, V. A., 1982, Immunizations: Current controversies, J. Pediatr. 101:487–494.PubMedCrossRefGoogle Scholar
  83. Fulginiti, V. A., and Kempe, C. H., 1963, Measles exposure among vaccine recipients, Am. J. Dis. Child. 106:450–461.PubMedGoogle Scholar
  84. Fung, P. Y. S., Madej, M., Koganty, R., and Longenecker, B. M., 1990, Active specific immunotherapy of a murine mammary adenocarcinoma using a synthetic tumor-associated glycoconjugate, Cancer Res. 50:4308–4314.PubMedGoogle Scholar
  85. Geiger, T., and Clarke, S., 1987, Deamidation, isomerization, and racemization of asparaginyl and aspartyl residues in peptides. Succinimide-linked reactions that contribute to protein degradation, J. Biol. Chem. 262:785–794.PubMedGoogle Scholar
  86. Gheorghiu, M., Mouton, D., Lecoeur, H., Lagranderie, M., Mevel, J. C., and Biozzi, G., 1985, Resistance of high and low antibody responder lines of mice to the growth of a virulent (BCG) and virulent (H37Rv) strains of mycobacteria, Clin. Exp. Immunol. 59:177–184.PubMedGoogle Scholar
  87. Gilley, R. M., Staas, J. K., Tice, T. R., Morgan, J. D., and Eldridge, J. H., 1992, Proc. Int. Symp. Control. Rel. Bioact. Mater. 19:110–111.Google Scholar
  88. Gillott, D. J., Nouri, A. M., Compton, S. J., and Oliver, R. T., 1993, Accurate and rapid assessment of MHC antigen upregulation following cytokine stimulation, J. Immunol. Methods 165:231–239.PubMedCrossRefGoogle Scholar
  89. Goldberg, A. L., and Rock, K. L., 1992, Proteolysis, proteosomes and antigen presentation, Nature 357:375–379.PubMedCrossRefGoogle Scholar
  90. Gorse, G. J., Patel, G., Mandava, M., Belshe, R., and the NIH NIAID AIDS Vaccine Clinical Trials Network, 1993, Cellular responses to T cell epitopes of HIV-1 envelope glycoprotein after vaccination with recombinant gp160 (rgp160), 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, Abstract 1135.Google Scholar
  91. Graham, B. S., Henderson, G. S., Tang, Y.-W., Lu, X., Neuzil, K. M., and Colley, D. G., 1993a, Priming immunization determines T helper cytokine mRNA expression patterns in lungs of mice challenged with respiratory syncytial virus, J. Immunol. 151:2032–2040.PubMedGoogle Scholar
  92. Graham, B. S., Keefer, M. C., McElrath, J., Matthews, T. J., Schwartz, D., Gorse, G. J., Sposto, R., Chernoff, D., and the NIH NIAID AIDS Vaccine Clinical Trials Network, 1993b, Phase I trial of native HIV-1SF2 rgp120 candidate vaccine, IX International Conference on AIDS, Berlin, Germany, Abstract PO-A29-0692.Google Scholar
  93. Gray, D., 1993, Immunological memory, Annu. Rev. Immunol. 11:49–77.PubMedCrossRefGoogle Scholar
  94. Gray, D., and Matzinger, P., 1991, T cell memory is short-lived in the absence of antigen, J. Exp. Med. 174:969–974.PubMedCrossRefGoogle Scholar
  95. Gray, D., and Sharvall, H., 1988, B-cell memory is short-lived in the absence of antigen, Nature 336:70–73.PubMedCrossRefGoogle Scholar
  96. Gray, D., and Sprent, J., 1990, Immunological memory, Curr. Top. Microbiol. Immunol. 159:1–141.PubMedCrossRefGoogle Scholar
  97. Graziosi, C., Pantaleo, G., Gantt, K. R., Fortin, J.-P., Demarest, J. F., Cohen, O. J., Sekaly, R. P., and Fausi, A. S., 1994, Lack of evidence for the dichotomy of Th1 and Th2 predominance for HIV-infected individuals, Science 265:248–252.PubMedCrossRefGoogle Scholar
  98. Green, J. D., and Terrell, T. G., 1992, Utilization of homologous proteins to evaluate the safety of recombinant human proteins — case study: Recombinant human interferon gamma (rhIFN-g), Toxicol. Lett. 64/65:321–327.CrossRefGoogle Scholar
  99. Gregoriadis, G., Davis, D., and Davis, A., 1987, Liposomes as immunological adjuvants, Vaccine 5:145–151.PubMedCrossRefGoogle Scholar
  100. Gu, L. C., Erdos, E. A., Chiang, H. S., Calderwood, T., Tsai, K., Visor, G. C., Duffy, J., Hsu, W. C., and Foster, L. C., 1991, Stability of interleukin 1 beta (IL-1 beta) in aqueous solution: Analytical methods, kinetics, products, and solution formulation implications, Pharm. Res. 8:485–490.PubMedCrossRefGoogle Scholar
  101. Hagan, P., Blumenthal, U. J., Dunne, D. W., Simpson, A. J. G., and Wilkins, H. A., 1991, Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium, Nature 349:243–245.PubMedCrossRefGoogle Scholar
  102. Haigwood, N. L., Nara, P. L., Brooks, E., Van Nest, G. A., Ott, G., Higgins, K. W., Dunlop, N., Scandella, C. J., Eichberg, J. W., and Steimer, K. S., 1992, Native but not denatured recombinant human immunodeficiency virus type I gp120 generates broad-spectrum neutralizing antibodies in baboons, J. Virol. 66:172–182.PubMedGoogle Scholar
  103. Hamburger, R., Azaz, E., and Donbrow, M., 1975, Autoxidation of polyoxyethylenic non-ionic surfactants and of polyethylene glycols, Pharm. Acta Helv. 50:10–17.PubMedGoogle Scholar
  104. Harding, C. V., Collins, D. S., Slot, J. W., Geuze, H. J., and Unanue, E. R., 1991, Liposome-encapsulated antigens are processed in lysomes, recycled and presented to T-cells, Cell 64:393–401.PubMedCrossRefGoogle Scholar
  105. Heath, A. W., and Playfair, J. H. L., (eds.), 1991, Vaccines 91, Cold Spring Harbor Press, Cold Spring Harbor, NY, pp. 351–354.Google Scholar
  106. Hellstrom, K. E., and Hellstrom, I., 1989, Oncogene-associated tumor antigens as targets for immunotherapy, FASEB J. 3:1715–1722.PubMedGoogle Scholar
  107. Herrington, D., Davis, J., Nardin, E. H., Beier, M., Cortese, J., Eddy, H., Losonsky, G., Hollingdale, M., Sztein, M., Levine, M., Nussenzweig, R. S., Clyde, D., and Edelman, R., 1991, Successful immunization of humans with irradiated malaria sporozoites: Humoral and cellular responses of the protected individuals, Am. J. Med. Hyg. 45:539–547.Google Scholar
  108. Hess, G., Hingst, V., Cseke, J., Bock, H. L., and Clemens, R., 1992, Influence of vaccination schedules and host factors on antibody response following hepatitis B vaccination, Eur. J. Clin. Microbiol. Infect. Dis. 11:334–340.PubMedCrossRefGoogle Scholar
  109. Hilleman, M. R., 1993, The promise and the reality of viral vaccines against cancer, Ann. NY. Acad. Sci. 690:6–18.PubMedCrossRefGoogle Scholar
  110. Hilleman, M. R., Buynak, E. B., Roehm, R. R., Tytell, A. A., Bertland, A. U., and Lampson, G. P., 1975, Purified and inactivated human hepatitis B vaccine: Progress report, Am. J. Med. Sci. 270:401–404.PubMedCrossRefGoogle Scholar
  111. Holmgren, J., Dzerkinsky, C., Lycke, N., and Svennerholm, A.-M., 1992, Mucosal immunity: Implications for vaccine development, Immunobiology 184:157–179.PubMedCrossRefGoogle Scholar
  112. Hora, M. S., Rana, R. K., Wilcox, C. L., Katre, N. V., Hirtzer, P., Wolfe, S. N., and Thomson, J. W., 1992, Development of a lyophilized formulation of interleukin-2, Dev. Biol. Stand. 74:295–303.PubMedGoogle Scholar
  113. Hou, S., Doherty, P. C., Zijlstra, M., Jaenisch, R., and Katz, J. M., 1992, Delayed clearance of Sendai virus in mice lacking class I MHC-restricted CD8+ T cells, J. Immunol. 149:1319–1325.PubMedGoogle Scholar
  114. Hou, S., Hyland, L., Ryan, K. W., Portner, A., and Doherty, P. C., 1994, Virus-specific CD8+ T-cell memory determined by clonal burst size, Nature 369:652–654.PubMedCrossRefGoogle Scholar
  115. Houbiers, J. G. A., Nijman, H. W., van der Burg, S. H., Drijfhout, J. W., Kenemans, P., van de Velde, C. J. H., Brand, A., Momburg, F., Kast, W. M., and Melief, C. J. M., 1993, In vitro induction of human cytotoxic T lymphocyte responses against peptides of mutant and wild-type p53, Eur. J. Immunol. 23:2072–2077.PubMedCrossRefGoogle Scholar
  116. Hubbard, R. D., Flory, C. M., and Collins, F. M., 1992a, Immunization of mice with mycobacterial culture filtrate proteins, Clin. Exp. Immunol. 87:94–98.PubMedCrossRefGoogle Scholar
  117. Hubbard, R. D., Flory, C. M., Collins, F. M., and Cocito, C., 1992b, Immunization of mice with the antigen A60 of Mycobacterium bovis BCG, Clin. Exp. Immunol. 88:129–131.PubMedCrossRefGoogle Scholar
  118. Hunt, D. F., Michel, H., Dickinson, T. A., Shabanowitz, J., Cox, A. L., Sakaguchi, K., Appella, E., Grey, H. M, and Sette, A., 1992, Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad, Science 256:660–662.Google Scholar
  119. Inazu, K., and Shima, K., 1992, Freeze drying and quality evaluation of protein drugs, Dev. Biol. Stand. 74:307–322.PubMedGoogle Scholar
  120. Insel, R. A., and Anderson, P. W., 1986, Oligosaccharide-protein conjugate vaccines induce and prime for oligoclonal IgG antibody responses to the H. influenzae b capsular Polysaccharide in human infants, J. Exp. Med. 163:262–269.PubMedCrossRefGoogle Scholar
  121. Ioannides, C. G., Fisk, B., Jerome, K. R., Irimura, T., Wharton, T., and Finn, O. J., 1993, Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides, J. Immunol. 151:3693–3703.PubMedGoogle Scholar
  122. Jackson, M. R., Cohen-Doyle, M. F., Peterson, P. A., and Williams, D. B., 1994, Regulation of MHC class I transport by the molecular chaperon, calnexin (p88, IP90), Science 263:384–387.PubMedCrossRefGoogle Scholar
  123. Jamieson, B. D., and Ahmed, R., 1989, T cell memory: Long-term persistence of virus-specific cytotoxic T cells, J. Exp. Med. 169:1993–2005.PubMedCrossRefGoogle Scholar
  124. Jerome, K. R., Barnd, D. L., Bendt, K. M., Boyer, C. M., Taylor-Papadimitriou, J., McKenzie, I. F. C., Bast, R. C., and Finn, O. J., 1991, Cytotoxic T-lymphocytes derived from patients with breast adenocarcinoma recognize an epitope present on the protein core of a mucin molecule preferentially expressed by malignant cells, Cancer Res. 51:2908–2916.PubMedGoogle Scholar
  125. Jerome, K. R., Domenech, N., and Finn, O. J., 1993, Tumor-specific cytotoxic T cell clones from patients with breast and pancreatic adenocarcinoma recognize EBV-immortalized B cells transfected with polymorphic epithelial mucin complementary DNA, J. Immunol. 161:1654–1662.Google Scholar
  126. Jertborn, M., Svennerholm, A.-M., and Holmgren, J., 1993, Evaluation of different immunization schedules for oral cholera B subunit-whole cell vaccine in Swedish volunteers, Vaccine 11:1007–1012.PubMedCrossRefGoogle Scholar
  127. Jilg, W., Bittner, R., Bock, H. L., Clemens, R., Schatzl, H., Schmidt, M., Andre, F. E., and Deinhardt, F., 1992, Vaccination against hepatitis A: Comparison of different short-term immunization schedules, Vaccine 10(Suppl.): 126–128.CrossRefGoogle Scholar
  128. Jin, Y., Shin, J. W. K., and Berkower, I., 1988, Human T cell response to the surface antigen of hepatitis B virus (HBsAg). Endosomal and nonendosomal processing pathways are accessible to both endogenous and exogenous antigen, J. Exp. Med. 168:293–296.PubMedCrossRefGoogle Scholar
  129. Johnson, D. M., and Gu, L. C., 1988, in: Encyclopedia of Pharmaceutical Technology, Vol. 1 (J. Swarbrick and J. C. Boylan, eds.), Dekker, New York, pp. 414–449.Google Scholar
  130. Jones, A. J. S., 1993, Analysis of Polypeptides and proteins, Adv. Drug Deliv. Rev. 10:29–90.CrossRefGoogle Scholar
  131. Jones, W. R., Bradley, J., Judd, S. J., Denholm, E. H., Ing, R. M. Y., Mueller, U. W., Powell, J., Griffin, P. D., and Stevens, V. C., 1988, Phase I clinical trial of a World Health Organization birth control vaccine, Lancet 1:1295–1298.PubMedCrossRefGoogle Scholar
  132. Just, M., Kanra, G., Bogaerts, H., Berger, R., Ceyhan, M., and Pêtre, J., 1991, Two trials of an acellular DTP vaccine in comparison with a whole-cell DTP vaccine in infants: Evaluation of two PT doses and two vaccination schedules, Dev. Biol. Stand. 73:275–283.PubMedGoogle Scholar
  133. Just, M., Berger, R., and Just, V., 1993, Reactogenicity and immunogenicity of a recombinant hepatitis B vaccine compared with a plasma-derived vaccine in young adults, Postgrad. Med. J. 63:121–123.Google Scholar
  134. Kalish, M. L., Check, I. J., and Hunter, R. L., 1991, Murine IgG isotype responses to the Plasmodium cynomolgi circumsporozoite peptide (NAGG)5. I. Effects on carrier, copolymer adjuvants, and lipopolysaccharide on isotype selection, J. Immunol. 146:3583–3590.PubMedGoogle Scholar
  135. Kapikian, A. Z., Mitchell, R. H., Chanock, R. M., Shvedoff, R. A., and Stewart, C. E., 1969, An epidemiological study of altered clinical reactivity to respiratory syncytial (RS) virus infection in children previously vaccinated with an inactivated RS vaccine, Am. J. Epidemiol. 89:405–421.PubMedGoogle Scholar
  136. Karagouni, E. E., and Hadjipetrou-Kourounakis, L., 1990, Regulation of isotype immunoglobulin production by adjuvants in vivo, Scand. J. Immunol. 31:745–754.PubMedCrossRefGoogle Scholar
  137. Kast, W. M., Bronkhorst, A. M., de Waal, L. P., and Melief, C. J. M., 1986, Cooperation between cytotoxic and helper T lymphocytes in protection against lethal Sendai virus infection, J. Exp. Med. 164:723–738.PubMedCrossRefGoogle Scholar
  138. Kaufmann, S. H. E., 1993, Immunity to intracellular bacteria, Annu. Rev. Immunol. 11:129–164.PubMedCrossRefGoogle Scholar
  139. Kayhty, H., Karanko, V, Peltola, H., and Makela, P. H., 1984, Serum antibodies after vaccination with H. influenzae type b capsular Polysaccharide and responses to reimmunization: No evidence of immunological tolerance or memory, Pediatrics 74:857–865.PubMedGoogle Scholar
  140. Kelly, A., Powis, S. H., Kerr, L.-A., Mockridge, I., Elliott, T., Bastin, J., Uchanska-Ziegler, B., Ziegler, A., and Townsend, A., 1992, Assembly and function of the two ABC transporter proteins encoded in the human major histocompatibility complex, Nature 355:641–644.PubMedCrossRefGoogle Scholar
  141. Kenney, J. S., Huges, B. W., Masada, M. P., and Allison, A. C., 1989, Influence of adjuvants on the quantity, affinity, isotype and epitope specificity of murine antibodies, J. Immunol. Methods 121:157–166.PubMedCrossRefGoogle Scholar
  142. Kensil, C. H., Patel, U., Lennick, M, and Marciani, D., 1991, Separation and characterization of saponins with adjuvant activity from Quillaja saponaria molina cortex, J. Immunol. 146:431–437.PubMedGoogle Scholar
  143. Kiefhaber, T., Rudolph, R., Kohler, H.-H., and Buchner, J., 1991, Protein aggregation in vitro and in vivo: A quantitative model of the kinetic competition between folding and aggregation, Biotechnology 9:825–830.PubMedCrossRefGoogle Scholar
  144. Kilbourne, E. D., 1988, Inactivated influenza vaccines, in: Vaccines (S. A. Plotkin and E. A. Mortimer, eds.), Saunders, Philadelphia, pp. 420–434.Google Scholar
  145. Kim, H. W., Canchola, J. G., Brandt, C. D., Pyles, G., Chanock, R. M., Jensen, K., and Parrott, R. H., 1969, Respiratory syncytial virus disease in infants despite prior administration of antigenic inactivated vaccine, Am. J. Epidemiol. 89:422–434.PubMedGoogle Scholar
  146. King, C. L., and Nutman, T. B., 1992, Biological role of helper T-cell subsets in helminth infections, Chem. Immunol. 54:136–165.PubMedCrossRefGoogle Scholar
  147. King, C. L., Low, C. C., and Nutman, T. B., 1993, IgE production in human helminth infection. Reciprocal interrelationship between IL-4 and IFNγ, J. Immunol. 150:1873–1880.PubMedGoogle Scholar
  148. Kruskall, M. S., Alper, C. A., Awdeh, Z., Yunis, E. J., and Marcus-Bagley, D., 1992, The immune response to hepatitis B vaccine in humans: Inheritance patterns in families, J. Exp. Med. 175:495–502.PubMedCrossRefGoogle Scholar
  149. Lanzavecchia, A., 1990, Receptor-mediated antigen uptake and its effect on antigen presentation to class II-restricted T lymphocytes, Annu. Rev. Immunol. 8:773–793.PubMedCrossRefGoogle Scholar
  150. LaRosa, G. J., David, J. P., Weinhold, K., Waterbury, J. A., Profy, A. T., Lewis, J. A., Langlois, A. J., Dreesman, G. R., Boswell, R. N., Shedduck, P., Holley, L. H., Kamplus, M., Bolognesi, D. P., Mathews, T. J., Emini, E. A., and Putney, S. D., 1990, Conserved sequences and structural elements in the HIV-1 principal neutralizing determinant, Science 249:932–935.PubMedCrossRefGoogle Scholar
  151. Lau, L. L., Jamieson, B. D., Somasundaram, T., and Ahmed, R., 1994, Cytotoxic T-cell memory without antigen, Nature 369:648–652.PubMedCrossRefGoogle Scholar
  152. Lee, W. T., and Vitetta, E. S., 1991, The differential expression of homing and adhesion molecules on virgin and memory T cells in the mouse, Cell. Immunol. 132:215–222.PubMedCrossRefGoogle Scholar
  153. Lehmann-Grube, F., Lohler, J., Utermohlen, O., and Gegin, C., 1993, Antiviral immune responses of lymphocytic choriomeningitis virus-infected mice lacking CD8+ T lymphocytes because of disruption of the β2-microglobulin gene, J. Virol. 67:332–339.PubMedGoogle Scholar
  154. Levine, M. M., Losonsky, G., Herrington, D., Kaper, J. B., Tacket, C., Rennels, M. B., and Morris, J. G., 1986, Pediatric diarrhea: The challenge of prevention, J. Pediatr. Infect. Dis. 5(Suppl.):29–43.CrossRefGoogle Scholar
  155. Liang, X., Lamm, M. E., and Nedrud, J. G., 1988, Oral administration of cholera toxin-Sendai virus conjugate potentiates gut and respiratory immunity against Sendai virus, J. Immunol. 141:1495–1501.PubMedGoogle Scholar
  156. Lidgate, D. M., Fu, R. C., Byars, N. E., Foster, L. C., and Fleitman, J. S., 1989, Formulation of vaccine adjuvant muramyldipeptides. 3. Processing optimization, characterization, and bioactivity of an emulsion vehicle, Pharm. Res. 6:748–752.PubMedCrossRefGoogle Scholar
  157. Lim, A., Cleland, J. L., Powell, M. F., Jacobsen, N., Basa, L., Spellman, M., Bedore, D., and Kensil, C. R., 1994, QS21 formulation stability and degradation products, Am. Assoc. Pharm. Sci. Meet., San Francisco.Google Scholar
  158. Linton, P.-J., and Klinman, N. R., 1992, The generation of memory B cells, Semin. Immunol. 4:3–9.PubMedGoogle Scholar
  159. Linton, P.-J., Decker, D. J., and Klinman, N. R., 1989, Primary antibody forming cells and secondary B cells are generated from separate precursor cell subpopulations, Cell 59:1049–1059.CrossRefGoogle Scholar
  160. Liu, W. R., Langer, R., and Klibanov, A. M., 1991, Moisture-induced aggregation of lyophilized proteins in the solid state, Biotechnol. Bioeng. 37:177–180.PubMedCrossRefGoogle Scholar
  161. Long, E. O., and Jacobson, S., 1989, Pathways of viral antigen processing and presentation to CTL, Immunol. Today 10:45–48.PubMedCrossRefGoogle Scholar
  162. Lubin, R., Schlichtholz, B., Bengoufa, D., Zalcman, G., Tredaniel, J., Hirsch, A., Caron de Fromentel, C., Preudhomme, C., Fenaux, P., Fournier, G., Mangin, P., Laurent-Puig, P., Pelletier, G., Schlumberger, M., Desgrandchamps, F., Le Duc, A., Peyrat, J. P., Janin, N., Bressac, B., and Soussi, T., 1993, Analysis of p53 antibodies in patients with various cancers define B cell epitopes of human p53: Distribution on primary structure and exposure on protein surface, Cancer Res. 53:5872–5876.PubMedGoogle Scholar
  163. McAleer, W. J., Buynak, E. B., Maigetter, R. Z., Wampler, D. E., Miller, W. J., and Hilleman, M. R., 1984, Human hepatitis B virus vaccine from recombinant yeast, Nature 307:178–180.PubMedCrossRefGoogle Scholar
  164. McElrath, M. J., Corey, L., Berger, D., Hoffman, M. C., Klucking, S., Dragavon, J., Peterson, E., and Greenberg, P. D., 1994, Immune responses elicited by recombinant vaccinia-human immunodeficiency virus (HIV) envelope and HIV envelope protein: Analysis of the durability of responses and effect of repeated boosting, J. Infect. Dis. 169:41–47.PubMedCrossRefGoogle Scholar
  165. McGhee, J. R., Fujihashi, K., Wu, A.-J., Elson, C. O., Beagley, K. W., and Kiyono, H., 1993, New perspectives in mucosal immunity with emphasis on vaccine development, Semin. Hematol. 30(4):3–12.PubMedGoogle Scholar
  166. Mackay, C. R., 1993, Immunological memory, Adv. Immunol. 53:217–265.PubMedCrossRefGoogle Scholar
  167. MacKenzie, J. S., 1977, Influenza subunit vaccine: Antibody responses to one and two doses of vaccine and length of response, with reference to the elderly, Br. Med. J. 1:200–202.PubMedCrossRefGoogle Scholar
  168. McKenzie, S. J., and Halsey, J. F., 1984, Cholera toxin B subunit as a carrier protein to stimulate a mucosal immune response, J. Immunol. 133:1818–1824.PubMedGoogle Scholar
  169. Madden, K. B., Urban, J. F., Ziltener, H. J., Schrader, J. W., Finkelman, F. D., and Katona, I. M., 1991, Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis, J. Immunol. 147:1387–1391.PubMedGoogle Scholar
  170. Maggi, E., Mazzetti, M., Ravina, A., Annunziato, F., De Carli, M., Piccinni, M. P., Manetti, R., Carbonari, M., Pesce, A. M., Del Prete, G., and Romagnani, S., 1994, Ability of HIV to promote a ThI to Th0 shift and to replicate preferentially in ThI to ThO cells, Science 265:244–248.PubMedCrossRefGoogle Scholar
  171. Mahanty, S., Abrams, J. S., King, C. L., Limaye, A. P., and Nutman, T. B., 1992, Parallel regulation of IL-4 and IL-5 in human helminth infections, J. Immunol. 148:3567–3571.PubMedGoogle Scholar
  172. Makela, P. H., Peltola, H., Kayhty, H., Jousimies, H., Pettay, O., Ruoslahti, E., Sivonen, A., and Renkonen, 1977, Polysaccharide vaccines of group A Neisseria meningitidis and Haemophilus influenzae type b: A field trial in Finland, J. Infect. Dis. 136(Suppl.):43–50.CrossRefGoogle Scholar
  173. Malik, A., Egan, J. E., Houghten, R. A., Sadoff, J. C., and Hoffman, S. L., 1991, Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein, Proc. Natl. Acad. Sci. USA 88:3300–3304.PubMedCrossRefGoogle Scholar
  174. Manning, M. C., Patel, K., and Borchardt, R. T., 1989, Stability of protein Pharmaceuticals, Pharm. Res. 6:903.PubMedCrossRefGoogle Scholar
  175. Martinez, C. K., and Monaco, J. J., 1991, Homology of proteasome subunits to a major histocompatibility complex-linked LMP gene, Nature 353:664–667.PubMedCrossRefGoogle Scholar
  176. Marx, P. A., Compans, R. W., Gettie, A., Staas, J. K., Gilley, R. M., Mulligan, M. J., Yamshchikov, G. V., Chen, D., and Eldridge, J. H., 1993, Protection against SIV transmission with microencapsulated vaccine, Science 260:1323–1327.PubMedCrossRefGoogle Scholar
  177. Maupas, P., Goudeau, A., Coursaget, P., Drucker, J., and Bagros, P., 1976, Immunization against hepatitis B in man, Lancet 1:1367–1370.PubMedCrossRefGoogle Scholar
  178. Miller, M. D., Gould-Fogerite, S., Shen, L., Woods, R. M., Koenig, S., Mannino, R. J., and Letvin, N. L., 1992, Vaccination of rhesus monkeys with synthetic peptide in a fusogenic proteoliposome elicits simian immunodeficiency virus-specific CD8+ cytotoxic T lymphocytes, J. Exp. Med. 176:1739–1744.PubMedCrossRefGoogle Scholar
  179. Millet, P., Collins, W. E., Broderson, J. R., Bathurst, I., Nardin, E. H., and Nussenzweig, R. S., 1991, Inhibitory activity against Plasmodium vivax sporozoites induced by plasma from Saimiri monkeys immunized with circumsporozoite recombinant proteins or irradiated sporozoites, Am. J. Trop. Med. Hyg. 45:44–48.PubMedGoogle Scholar
  180. Modlin, R. L., and Nutman, T. B., 1993, Type 2 cytokines and negative immune regulation in human infections, Curr. Opin. Immunol. 5:511–517.PubMedCrossRefGoogle Scholar
  181. Mollica, J. A., Ahuja, S., and Cohen, J., 1978, Stability of Pharmaceuticals, J. Pharm. Sci. 67:443–465.PubMedCrossRefGoogle Scholar
  182. Monaco, J. J., Cho, S., and Attaya, M., 1990, Transport proteins in the murine MHC: Possible implications for antigen processing, Science 250:1723–1726.PubMedCrossRefGoogle Scholar
  183. Mordenti, J., Nguyen, T., Eastman, D., Osaka, G., Frie, S., Weissburg, R. P., Berman, P. W., Abramowitz, P., DiStefano, J., III, and Powell, M. F., 1994, Effects of alum on i.m. absorption and immunogenicity of MN rgp120 in rabbits, Am. Assoc. Pharm. Sci. Meet., San Francisco.Google Scholar
  184. Morefield, E. M., Peck, G. E., Feldkamp, J. R., White, J. L., and Hem., S. L., 1986, Role of water in the aging of aluminum hydroxide suspensions, J. Pharm. Sci. 75:403–406.PubMedCrossRefGoogle Scholar
  185. Moreno, A., Clavijo, P., Edelman, R., Davis, J., Sztein, M., Herrington, D., and Nardin, E., 1991, Cytotoxic CD4+ T cells from a sporozoite-immunized volunteer recognize the Plasmodium falciparum CS protein, Int. Immunol. 3:997–1003.PubMedCrossRefGoogle Scholar
  186. Mortimer, E. A., 1988a, Diphtheria toxoid, in: Vaccines (S. A. Plotkin and E. A. Mortimer, eds.), Saunders, Philadelphia, pp. 31–44.Google Scholar
  187. Mortimer, E. A., 1988b, Pertussis vaccine, in: Vaccines (S. A. Plotkin and E. A. Mortimer, eds.), Saunders, Philadelphia, pp. 74–97.Google Scholar
  188. Moskophidis, D., Lechner, F., Pircher, H., and Zinkernagel, R. M., 1993, Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells, Nature 362:758–761.PubMedCrossRefGoogle Scholar
  189. Mosmann, T. R., and Coffman, R. L., 1989, TH1 and TH2 cells: Different patterns of lymphokine secretion lead to different functional properties, Annu. Rev. Immunol. 7:145–173.PubMedCrossRefGoogle Scholar
  190. Mosmann, T. R., Cherwinski, H., Bond, M. W, Gieldlin, M. A., and Coffman, R. L., 1986, Two types of murine helper T cell clones: 1. Definition according to profiles of lymphokine activities and secreted proteins, J. Immunol. 136:2348–2357.PubMedGoogle Scholar
  191. Mountford, A. P., Coulson, P. S., Pemberton, R. M., Smythies, L. E., and Wilson, R. A., 1992, The generation of interferon-γ-producing T lymphocytes in skin-draining lymph nodes, and their recruitment to the lungs, is associated with protective immunity to Schistosoma mansoni, Immunology 75:250–256.PubMedGoogle Scholar
  192. Muller, D., Koller, B. H., Whitton, J. L., LaPan, K. E., Brigman, K. K., and Frelinger, J. A., 1992, LCMV-specific, class II-restricted cytotoxic T cells in β2-microglobulin-deficient mice, Science 255:1576–1578.PubMedCrossRefGoogle Scholar
  193. Müller, R., Chriske, H., Deinhardt, J. J., Jilg, J., Theilmann, L., Hess, G., Hofmann, F., Hopf, U., Stickl, H., and Mainwald, H., 1992, Hepatitis A vaccination: Schedule for accelerated immunization, Vaccine 10(Suppl.): 124–145.CrossRefGoogle Scholar
  194. Murphy, F. A., and Kingsbury, D. W., 1990, Virus taxonomy, in: Virology, Vol. 1 (B. N. Fields and D. M. Knipe, eds.), Raven Press, New York, pp. 9–35.Google Scholar
  195. Mustafa, A. S., Lundin, K. E. A., and Oftung, F., 1993, Human T cells recognize mycobacterial heat shock proteins in the context of multiple HLA-DR molecules: Studies with healthy subjects vaccinated with Mycobacterium bovis BCG and Mycobacterium leprae, Infect. Immun. 61:5294–5301.PubMedGoogle Scholar
  196. Nail, S. L., White, J. L., and Hem, S. L., 1976, Structure of aluminum hydroxide gel II. Aging mechanism, J. Pharm. Sci. 65:1192–1195.PubMedCrossRefGoogle Scholar
  197. Nardin, E. H., and Nussenzweig, R. S., 1993, T cell responses to pre-erythrocytic stages of malaria: Role in protection and vaccine development against pre-erythrocytic stages, Annu. Rev. Immunol. 11:687–727.PubMedCrossRefGoogle Scholar
  198. Nardin, E. H., Herringon, D. A., Davis, J., Levine, M., Stuber, D., Takacs, B., Caspers, P., Barr, P., Altszuler, R., Clavijo, P., and Nussenzweig, R. S., 1989, Conserved repetitive epitope recognized by CD4+ clones from a malaria immunized volunteer, Science 246:1603–1606.PubMedCrossRefGoogle Scholar
  199. Nardin, E. S., Clavijo, P., Mons, B., van Belkum, A., Ponnudurai, T., and Nussenzweig, R. S., 1991, T cell epitopes of the circumsporozoite protein of Plasmodium vivax. Recognition by lymphocytes of a sporozoite-immunized chimpanzee, J. Immunol. 146:1674–1678.PubMedGoogle Scholar
  200. Neefjes, J. J., Stollorz, V, Peters, P. J., Geuze, H. J., and Ploegh, H. L., 1990, The biosynthetic pathway of MHC class II but not class I molecules intersects the endocytic route, Cell 61:171–183.PubMedCrossRefGoogle Scholar
  201. Newman, M. J., Wu, J.-Y., Gardner, B. H., Munroe, K. J., Leombruno, D., Recchia, J., Kensil, C. R., and Coughlin, R. T., 1992, Saponin adjuvant induction of ovalbumin-specific CD8+ cytotoxic T lymphocyte responses, J. Immunol. 148:2357–2362.PubMedGoogle Scholar
  202. Nijman, H. W., Houbiers, J. G. A., van der Burg, S. H., Vierboom, M. P. M., Kenemans, P., Kast, W. M., and Melief, C. J. M, 1993, Characterization of cytotoxic T lymphocyte epitopes of a self-protein, p53, and a non-self-protein, influenza matrix: Relationship between major histocompatibility complex peptide binding affinity and immune responsiveness to peptides, J. Immunother. 14:121–126.CrossRefGoogle Scholar
  203. Nommensen, F. E., Go, S. T., and MacLaren, D. M., 1989, Half-life of HBs antibody after hepatitis B vaccination: An aid to timing of booster vaccination, Lancet 2:847–849.PubMedCrossRefGoogle Scholar
  204. Norde, W., and Lyklema, J., 1991, Why proteins prefer interfaces, J. Biomater. Sci. Polym. Ed. 2:183–202.PubMedCrossRefGoogle Scholar
  205. Nuchtern, J. G., Biddison, W. E., and Klausner, R. D., 1990, Class II MHC molecules can use the endogenous pathway of antigen presentation, Nature 343:11–14.CrossRefGoogle Scholar
  206. Oehen, S., Waldner, H., Kundig, T. M., Hengartner, H., and Zinkernagel, R. M., 1992, Antivirally protective cytotoxic T cell memory lymphocytic choriomeningitis virus is governed by persisting antigen, J. Exp. Med. 176:1273–1281.PubMedCrossRefGoogle Scholar
  207. Ogle, J. D., Noel, J. G., Balasubramaniam, A., Sramoski, R. M., Ogle, C. K., and Alexander, J. W., 1990, Comparison of abilities of recombinant interleukin-1 alpha and-beta and noninflammatory IL-1 beta fragment 163–171 to upregulate C3b receptors (CR1) on human neutrophils and to enhance their phagocytic capacity, Inflammation 14:185–194.PubMedCrossRefGoogle Scholar
  208. Orme, I. M., and Collins, F. M., 1983, Protection against Mycobacterium tuberculosis infection by adoptive immunotherapy. Requirement for T cell-deficient recipients, J. Exp. Med. 158:74–83.PubMedCrossRefGoogle Scholar
  209. Pal, P. G., and Horwitz, M. A., 1992, Immunization with extracellular proteins of Mycobacterium tuberculosis induces cell-mediated immune responses and substantial protective immunity in a guinea pig model of pulmonary tuberculosis, Infect. Immun. 60:4781–4792.PubMedGoogle Scholar
  210. Pamer, E. G., 1993, Cellular immunity to intracellular bacteria, Curr. Opin. Immunol. 5:492–496.PubMedCrossRefGoogle Scholar
  211. Parronchi, P., Macchia, D., Piccinni, M. P., Biswas, P., Simonelli, C., Maggi, E., Ricci, M., Ansari, A. A., and Romagnani, S., 1991, Allergen-and bacterial antigen-specific T cell clones established from atopic donors show a different profile of cytokine production, Proc. Natl. Acad. Sci. USA 88:4538–4542.PubMedCrossRefGoogle Scholar
  212. Paul, W. E., and Seder, R. A., 1994, Lymphocyte responses and cytokines, Cell 76:241–251.PubMedCrossRefGoogle Scholar
  213. Peace, D. J., Chen, W., Nelson, H., and Cheever, M. A., 1991, T-cell recognition of transforming proteins encoded by mutated ras proto-oncogenes, J. Immunol. 146:2059–2065.PubMedGoogle Scholar
  214. Pearlman, R., and Nguyen, T., 1992, Pharmaceutics of protein drugs, J. Pharm. Pharmacol. 44:178–185.PubMedGoogle Scholar
  215. Penney, C. L., Landi, S., Shah, P., Leung, K. H., and Archer, M. C., 1986, Analysis of the immunoadjuvant octadecyl tyrosine hydrochloride, J. Biol. Stand. 14:345–349.PubMedCrossRefGoogle Scholar
  216. Peters, P. J., Neefjes, J. J., Oorschot, V., Ploegh, H. L., and Geuze, H. J., 1991, Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to the lysosomal compartments, Nature 349:669–676.PubMedCrossRefGoogle Scholar
  217. Philipson, L., 1962, Oxidation of 2,3-dimercaptopropranol, Biochim. Biophys. Acta 56:375–381.CrossRefGoogle Scholar
  218. Pierce, N. F., 1984, Induction of optimal mucosal antibody responses: Effects of age, immunization route(s), and dosing schedule in rats, Infect. Immun. 43:341–346.PubMedGoogle Scholar
  219. Pikal, M. J., 1990, Freeze-drying of proteins — Part II: Formulation selection, Biopharm. 3:26–30.Google Scholar
  220. Pikal, M. J., 1993, Freeze drying of proteins: Process, formulation, and stability, Protein Formulations and Delivery Symposium, 205th American Chemical Society Meeting (abstract).Google Scholar
  221. Pikal, M. J., Dellerman, K., and Roy, M. L., 1991a, Formulation and stability of freeze-dried proteins: Effects of moisture and oxygen on the stability of freeze-dried formulations of human growth hormone, Dev. Biol. Stand. 74:21–27.Google Scholar
  222. Pikal, M. J., Dellerman, K. M., Roy, M. L., and Riggin, R. M., 1991b, The effects of formulation variables on the stability of freeze-dried human growth hormone, Pharm. Res. 8:427–436.PubMedCrossRefGoogle Scholar
  223. Piszkiewicz, D., Landon, M., and Smith, E. L., 1970, Anomalous cleavage of aspartyl-proline peptide bonds during amino acid sequence determinations, Biochem, Biophys. Res. Commun. 40:1173–1178.CrossRefGoogle Scholar
  224. Pithie, A. D., Rahelu, M., Kumararatne, D. S., Drysdale, P., Gaston, J. S. H., Iles, P. B., Innes, J. A., and Ellis, C. J., 1992, Generation of cytolytic T cells in individuals infected by Mycobacterium tuberculosis and vaccinated with BCG, Thorax 47:695–701.PubMedCrossRefGoogle Scholar
  225. Plotkin, S. A., and Mortimer, E. A., (eds.), 1988, Vaccines, Saunders, Philadelphia.Google Scholar
  226. Powell, M. F., 1994, Peptide stability in aqueous parenteral formulations: Prediction of chemical stability based on primary sequence, in: Protein Formulations and Delivery (J. L. Cleland and R. S. Langer, eds.), American Chemical Society Symposium Series 567:100–117.CrossRefGoogle Scholar
  227. Powell, M. F., Foster, L. C., Becker, A. R., and Lee, W., 1988, Formulation of vaccine adjuvant muramyldipeptides (MDP). 2. The thermal reactivity and pH of maximum stability of MDP compounds in aqueous solution, Pharm. Res. 5:528–532.PubMedCrossRefGoogle Scholar
  228. Powell, M. F., Eastman, D. J., Lim, A., Lucas, C., Peterson, M., Vennari, J., Weissburg, R. P., Wrin, T., Kensil, C., Newman, M. J., Nunberg, J. H., Cleland, J. L., Gregory, T., and Berman, P. W., 1995, Effect of adjuvants on the immunogenicity of the MN rgp120 vaccine in guinea pigs, AIDS Res. Hum. Retroviruses (in press).Google Scholar
  229. Preblud, R., and Katz, S. L., 1988, Measles vaccine, in: Vaccines (S. A. Plotkin and E. A. Mortimer, eds.), Saunders, Philadelphia, pp. 182–234.Google Scholar
  230. Preis, I., and Langer, R. S., 1979, A single shot immunization by sustained antigen release, J. Immunol. Methods 28:193–197.PubMedCrossRefGoogle Scholar
  231. Prestrelski, S. J., Tedeschi, N., Carpenter, J. F., and Arakawa, T., 1993, Dehydration-induced conformational transitions in proteins and their inhibitors, Biophys. J. 65:661–671.PubMedCrossRefGoogle Scholar
  232. Pullano, T. G., Sinn, E., and Carney, W. P., 1989, Characterization of monoclonal antibody R256, specific for the activated ras p21 with arginine at 12, and analysis of breast carcinoma for v-Harvey-ras transgenic mouse, Oncogene 4:1003–1008.PubMedGoogle Scholar
  233. Pupa, S. M., Menard, S., Andreola, S., and Colnaghi, M. I., 1993, Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients, Cancer Res. 53:5864–5866.PubMedGoogle Scholar
  234. Rajewsky, K., 1992, Early and late B-cell development in the mouse, Curr. Opin. Immunol. 4:171–176.PubMedCrossRefGoogle Scholar
  235. Ramon, G., 1926, Procedes pour accroitre 1a production des antioxines, Ann. Inst. Pasteur 40:1–10.Google Scholar
  236. Reed, S. G., and Scott, P., 1993, T cell and cytokine responses in leishmaniasis, Curr. Opin. Immunol. 5:524–531.PubMedCrossRefGoogle Scholar
  237. Ribero, D. E., Jesus, A. M., Almeida, R. P., Bacelar, O., Araujo, M. I., Demeure, C., Bina, J. C., Dessein, A. J., and Carvalho, E. M., 1993, Correlation between cell-mediated immunity and degree of infection in subjects living in an endemic area of Schistosomiasis, Eur. J. Immunol. 23:152–158.CrossRefGoogle Scholar
  238. Ridley, D. S., and Jopling, W. H., 1966, Classification of leprosy according to immunity. A five-group system, Int. J. Lepr. 34:255–273.Google Scholar
  239. Robinson, A. B., and Rudd, C. J., 1974, in: Current Topics in Cellular Regulations, Vol. 8 (B. L. Horecker and E. R. Stadtman, eds.), Academic Press, New York, pp. 247–295.Google Scholar
  240. Robinson, A. B., Scotchler, J. W., and McKerrow, J. H., 1973, Rates of nonenzymatic deamidation of glutaminyl and asparaginyl residues in pentapeptides, J. Am. Chem. Soc. 95:8156–8159.PubMedCrossRefGoogle Scholar
  241. Rocha, C. L., Murillo, L. A., Mora, A. L., Rojas, M., Franco, L., Cote, J., Valero, M. V., Moreno, A., Amador, R., Nunez, F., Coronell, C., and Patarroyo, M. C., 1992, Determination of the immunization schedule for field trials with the synthetic malaria vaccine SPf 66, Parasite Immunol. 14:95–109.PubMedCrossRefGoogle Scholar
  242. Rolink, A., and Melchers, F, 1991, Molecular and cellular origins of B lymphocyte diversity, Cell 66:1081–1094.PubMedCrossRefGoogle Scholar
  243. Rotzschke, O., Falk, K., Deres, O., Schild, H., Norda, M., Metzger, J., Jung, G., and Rammensee, H.-G., 1990, Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells, Nature 348:252–253.PubMedCrossRefGoogle Scholar
  244. Rudensky, A. Y., Preston-Hurlburt, P., Al-Ramadi, B. K., Rothbard, J., and Janeway, C. A., 1992, Truncation of variants of peptides isolated from MHC class II molecules suggest sequence motifs, Nature 359:429–431.PubMedCrossRefGoogle Scholar
  245. Sadana, A., 1992, Protein adsorption and inactivation on surfaces. Influence of heterogeneities, Chem. Rev. 92:1799–1807.CrossRefGoogle Scholar
  246. Saint-Leger, D., Bague, A., Cohen, E., and Chivot, M., 1986, A possible role for squalene in the pathogenesis of acne. I. In vitro study of squalene oxidation, Br. J. Dermatol. 114:535–542.PubMedCrossRefGoogle Scholar
  247. Salgame, P., Abrams, J. S., Clayberger, C., Goldstein, H., Convit, J., Modlin, R. L., and Bloom, B. R., 1991, Differing lymphokine profiles of functional subsets of human CD4 and CD8 T cell clones, Science 254:279–282.PubMedCrossRefGoogle Scholar
  248. Salk, D., van Wezel, A. L., and Salk, J., 1984, Induction of long term immunity to paralytic poliomyelitis by use of a non-infectious vaccine, Lancet 2:1317–1321.PubMedCrossRefGoogle Scholar
  249. Salk, J. E., 1955, Considerations in the preparation and use of poliomyelitis virus vaccine, J. Am. Med. Assoc. 158:1239–1248.PubMedCrossRefGoogle Scholar
  250. Salk, J., and Drucker, J., 1988, Noninfectious poliovirus vaccine, in: Vaccines (S. A. Plotkin and E. A. Mortimer, eds.), Saunders, Philadelphia, pp. 158–181.Google Scholar
  251. Sato, S., Ebert, C. D., and Kim, S. W., 1984, Prevention of insulin self-association and surface adsorption, J. Pharm. Sci. 72:228–232.CrossRefGoogle Scholar
  252. Scherle, P. A., Palladino, G., and Gerhard, W., 1992, Mice can recover from pulmonary influenza virus infection in the absence of class I-restricted cytotoxic T cells, J. Immunol. 148:212–217.PubMedGoogle Scholar
  253. Schneerson, R., Robbins, J. B., Parke, J. C., Parke, J. C., Bell, C., Schlesselman, J. J., Sutton, A., Wang, Z., Schiffman, G., Karpas, A., and Shiloach, J., 1986, Quantitative and qualitative analyses of serum antibodies elicited in adults by H. influenzae type b and pneumococcus type 6A capsular polysaccharidetetanus toxoid conjugates, Infect. Immun. 52:519–528.PubMedGoogle Scholar
  254. Schultz, J., 1967, Cleavage at aspartic acid, Methods Enzymol. 11:255–263.CrossRefGoogle Scholar
  255. Seeber, S. J., White, J. L., and Hem, S. L., 1991, Solubilization of aluminum-containing adjuvants by constituents of interstitial fluid, J. Parenter. Sci. Technol. 45:156–159.PubMedGoogle Scholar
  256. Sette, A., Buus, S., Colon, C., Miles, C., and Grey, H. M., 1988, 1-Ad binding peptides derived from unrelated proteins share a common structural motif,J. Immunol. 141:45–48.PubMedGoogle Scholar
  257. Shearer, G. M., and Clerici, M., 1992, T helper cell immune dysfunction in asymptomatic, HIV-1-seropositive individuals: The role of TH1–TH2 cross-regulation, Chem. Immunol. 54:21–43.PubMedCrossRefGoogle Scholar
  258. Sher, A., and Coffman, R. L., 1992, Regulation of immunity to parasites by T cells and T cell-derived cytokines, Annu. Rev. Immunol. 10:385–409.PubMedCrossRefGoogle Scholar
  259. Shirodkar, S., Hutchinson, R. L., Perry, D. L., White, J. L., and Hem, S. L., 1990, Aluminum compounds used as adjuvants in vaccines, Pharm. Res. 7:1282.PubMedCrossRefGoogle Scholar
  260. Sieling, P. A., Abrams, J. S., Yamamura, M., Salgame, P., Bloom, B. R., Rea, T. H., and Modlin, R. L., 1993, Immunosuppressive roles for interleukin-10 and interleukin-4 in human infection: In vitro modulation of T cell responses in leprosy, J. Immunol. 150:5501–5510.PubMedGoogle Scholar
  261. Sluzky, V., Tamada, J., Klibanov, A. M., and Langer, R., 1991, Kinetics of insulin aggregation in aqueous solutions upon agitation in the presence of hydrophobic surfaces, Proc. Natl. Acad. Sci. USA 88:9377–9381.PubMedCrossRefGoogle Scholar
  262. Smith, D. H., Peter, G., and Ingram, D. L., 1973, Responses of children immunized with the capsular Polysaccharide of H. influenza, type b, Pediatrics 52:637–644.PubMedGoogle Scholar
  263. Smith, D. W, Wiegeshaus, E. H., and Edwards, M. L., 1988, The protective effects of BCG vaccination against tuberculosis, in: Mycobacterium tuberculosis Interactions with the Immune System (M. Bendinelli and H. Friedman, eds.), Plenum Press, New York, pp. 341–370.CrossRefGoogle Scholar
  264. Smythies, L. E., Coulson, P. S., and Wilson, R. A., 1992a, T cell-derived cytokines associated with pulmonary immune mechanisms in mice vaccinated with irradiated cercariae of Schistosoma mansoni, J. Immunol. 148:1512–1518.PubMedGoogle Scholar
  265. Smythies, L. E., Coulson, P. S., and Wilson, R. A., 1992b, Monoclonal antibody to IFN-y modifies pulmonary inflammatory responses and abrogates immunity to Schistosoma mansoni in mice vaccinated with attenuated cercariae, J. Immunol. 149:3654–3658.PubMedGoogle Scholar
  266. Spies, T., Cerundolo, V., Colonna, M., Cresswell, P., Townsend, A., and DeMars, R., 1992, Presentation of viral antigen by class I MHC molecules is dependent on a putative peptide transporter heterodimer, Nature 355:644–646.PubMedCrossRefGoogle Scholar
  267. Sprent, J. T., 1994, T and B memory cells, Cell 76:315–322.PubMedCrossRefGoogle Scholar
  268. Stadtman, E. R., 1990, Metal ion-catalyzed oxidation of proteins: Biochemical mechanism and biological consequences, Free Radical Biol. Med. 9:315–325.CrossRefGoogle Scholar
  269. Steadman, B. L., Thompson, K. C., Middaugh, C. R., Matsuno, K., Vrona, S., Lawson, E. Q., and Lewis, R. V., 1992, The effects of surface adsorption on the thermal stability of proteins, Biotechnol. Bioeng. 40:8–12.PubMedCrossRefGoogle Scholar
  270. Steiner, L. A., and Eisen, H. N., 1967, The relative affinity of antibodies synthesized in the secondary response, J. Exp. Med. 126:1185–1205.PubMedCrossRefGoogle Scholar
  271. Stevens, T. L., Bossie, A., Sanders, V. M, Fernandez-Botran, R., Coffman, R. L., Mosmann, T. R., and Vitetta, E. S., 1988, Regulation of antibody isotype secretion by subsets of antigen-specific helper T cells, Nature 334:255–258.PubMedCrossRefGoogle Scholar
  272. Stevens, V. C., and Jones, W. R., 1990, Vaccines to prevent pregnancy, in: New Generation Vaccines (G. C. Woodrow and M. M. Levine, eds.), Dekker, New York, pp. 879–990.Google Scholar
  273. Stewart, M. J., Nawrot, R., Schulman, S., and Vanderberg, J. P., 1986, Plasmodium berghei sporozoite invasion is blocked in vitro by sporozoite-immobilizing antibodies, Infect. Immun. 51:859–864.PubMedGoogle Scholar
  274. Stürchler, D., Berger, R., Etlinger, H., Matile, H., Pink, R., Schlumbom, and Just, M., 1989, Effects of interferons on immune response to a synthetic peptide malaria sporozoite vaccine in non-immune adults, Vaccine 7:457–461.PubMedCrossRefGoogle Scholar
  275. Suh, W.-K., Cohen-Doyle, M. F., Fruh, K., Wang, K., Peterson, P. A., and Williams, D. B., 1994, Interaction of MHC class I molecules with the transporter associated with antigen processing, Science 264:1322–1326.PubMedCrossRefGoogle Scholar
  276. Swain, S. L., Weinberg, A. D., and English, M., 1990, CD4+ Tcell subsets: Lymphokine secretion of memory cells and of effector cells that develop from precursors in vitro, J. Immunol. 144:1788–1799.PubMedGoogle Scholar
  277. Swain, S. L., Bradley, L. M., Croft, M., Tonkonogy, S., Atkins, G., Weinberg, A. D., Duncan, D. D., Hedrick, S. M, Dutton, R. W., and Huston, G., 1991, Helper T-cell subsets: Phenotype, function and the role of lymphokines in regulating their development, Immunol. Rev. 123:115–144.PubMedCrossRefGoogle Scholar
  278. Tai, J. Y., Vella, P., McLean, A. A., Woodhour, A. F., McAleer, W. J., Sha, A., Dennis-Sykes, C., and Hilleman, M. R., 1987, H. influenzae type b polysaccharide-protein conjugate vaccine, Proc. Soc. Exp. Biol. Med. 184:154–161.PubMedGoogle Scholar
  279. Teh, L. C., Murphy, L. J., Huq, N. L., Surus, A. S., Friesen, H. G., Lazarus, L., and Chapman, G. E., 1987, Methionine oxidation in human growth hormone and human chorionic somatomammotropin. Effects on receptor binding and biological activities, J. Biol. Chem. 262:6472.PubMedGoogle Scholar
  280. Terrell, T. G., and Green, J. D., 1993, Comparative pathology of recombinant murine interferon-g in mice and recombinant human interferon-g in cynomolgus monkeys, Int. Rev. Exp. Pathol. 34B:73–101.Google Scholar
  281. Tsicopoulos, A., Hamid, Q., Varney, V., Ying, S., Moqbel, R., Durham, S. R., and Kay, B., 1992, Preferential messenger RNA suppression of Th 1-type cells (IFN-y+, IL-2+) in classical delayed-type (tuberculin) hypersensitivity reaction in human skin, J. Immunol. 148:2058–2061.PubMedGoogle Scholar
  282. Tsutsui, H., Mizoguchi, Y, and Morisawa, S., 1991, There is no correlation between function and lymphokine production of HBs-antigen-specific human CD4(+)-cloned T cells, Scand. J. Immunol. 34:433–444.PubMedCrossRefGoogle Scholar
  283. Urban, J. F., Katona, I. M., Paul, W. E., and Finkelman, F. D., 1991, Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice, Proc. Natl. Acad. Sci. USA 88:5513–5517.PubMedCrossRefGoogle Scholar
  284. Urban, J. F., Madden, K. B., Svetic, A., Cheever, A., Trotta, P. P., Gause, W. C., Katona, I. M., and Finkelman, F. D., 1992, The importance of TH2 cytokines in protective immunity to nematodes, Immunol. Rev. 127:205–220.PubMedCrossRefGoogle Scholar
  285. van Bleek, G. M., and Nathenson, S. G., 1990, Isolation of an endogenously processed immunodominant viral peptide from the class I H-2Kb molecule, Nature 348:213–216.PubMedCrossRefGoogle Scholar
  286. Van Nest, G. A., Steimer, K. S., Haigwood, N. L., Burke, R. L., and Ott, G., 1992, Advanced adjuvant formulations for use with recombinant subunit vaccines, in: Vaccines 92, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp. 57–62.Google Scholar
  287. van Noort, J. M., Boon, J., Van der Drift, A. C. M., Wagenaar, J. P. A., Boot, A. M. H., and Goog, C. J. P., 1991, Antigen processing by endosomal proteases determines which sites on sperm-whale myoglobin are eventually recognized by T cells, Eur. J. Immunol. 21:1989–1996.PubMedCrossRefGoogle Scholar
  288. Vidard, L., Rock, K. L., and Benacerraf, B., 1991, The generation of immunogenic peptides can be selectively increased or decreased by proteolytic enzyme inhibitors, J. Immunol. 147:1786–1791.PubMedGoogle Scholar
  289. Vingerhoets, J., Vanham, G., Kestens, L., Penne, G., Leroux-Roels, G., and Gigase, P., 1994, Deficient T-cell responses in non-responders to hepatitis B vaccination: Absence of TH1 cytokine production. Immunol. Lett. 39:163–168.PubMedCrossRefGoogle Scholar
  290. Wang, Y.-C. J., and Hanson, M. A., 1988, Parenteral formulations of proteins and peptides. Stability and stabilizers, J. Parent er. Sci. Technol. 42(Suppl.):2–26.Google Scholar
  291. Wassilak, S. G. F., and Orenstein, W. A., 1988, Tetanus, in: Vaccines (S. A. Plotkin and E. A. Mortimer, eds.), Saunders, Philadelphia, pp. 45–73.Google Scholar
  292. Webster, R. G., 1968, The immune response to influenza virus: II. Effect of the route and schedule of vaccination on the quantity and avidity of antibodies, Immunology 14:29–37.PubMedGoogle Scholar
  293. Weibel, R. E., 1988, Mumps vaccine, in: Vaccines (S. A. Plotkin and E. A. Mortimer, eds.), Saunders, Philadelphia, pp. 223–234.Google Scholar
  294. Weinberg, A., and Merigan, T. C., 1988, Recombinant interleukin-2 as an adjuvant for vaccine induced protection, J. Immunol. 140:294–299.PubMedGoogle Scholar
  295. Westblom, T. U., Gudipati, S., DeRousse, C., Midkiff, B. R., and Belshe, R. B., 1994, Safety and immunogenicity of an inactivated hepatitis A vaccine: Effect of dose and vaccination schedule, J. Infect. Dis. 169:996–1001.PubMedCrossRefGoogle Scholar
  296. Wiedermann, G., Ambrosch, F., Kremsner, P., Kunz, C., Hauser, P., Simoen, E., André, F., and Safary, A., 1987a, Reactogenicity and immunogenicity of different lots of a yeast-derived hepatitis B vaccine, Postgrad. Med. J. 63:109–112.PubMedGoogle Scholar
  297. Wiedermann, G., Ambrosch, F., Kollaritsch, H., Hofmann, H., Kunz, C., Hondt, E. D., Delem, A., André, F. E., Safary, A., and Stephenne, J., 1987b, Safety and immunogenicity of an inactivated hepatitis A candidate vaccine in healthy adult volunteers, Postgrad. Med. J. 63:109–112.PubMedGoogle Scholar
  298. Wikel, S. K., 1988, Immunological control of hematophagous arthropod vectors: Utilization of novel antigens, Vet. Parasitol. 29:235–264.PubMedCrossRefGoogle Scholar
  299. Willadsen, P., Eisemann, C. H., and Tellam, R. L., 1993, “Concealed” antigens: Expanding the range of immunological targets, Parasitol. Today 9:132–135.PubMedCrossRefGoogle Scholar
  300. Wilson, R. A., 1993, Immunity and immunoregulation in helminth infections, Curr. Opin. Immunol. 5:538–547.PubMedCrossRefGoogle Scholar
  301. Wright, H. T., 1991, Nonenzymatic deamidation of asparaginyl and glutaminyl residues in proteins, CRC Cht. Rev. Biochem. Mol. Biol. 26:1–52.CrossRefGoogle Scholar
  302. Wu, J.-Y., Gardiner, B. H., Murphy, C. I., Seals, J. R., Kensil, C. H., Recchia, J., Beltz, G. A., Newman, G. W., and Newman, M. J., 1992, Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine, J. Immunol. 148:1519–1525.PubMedGoogle Scholar
  303. Yamamura, M., Uyemura, K., Deans, R. J., Weinberg, K., Rea, T. H., Bloom, B. R., and Modlin, R. L., 1991, Defining protective responses to pathogens: Cytokine profiles in leprosy lesions, Science 254:277–279.PubMedCrossRefGoogle Scholar
  304. Yamamura, M., Wang, X.-H., Ahmen, J. D., Uyemura, K., Rea, T. H., Blom, B. R., and Modlin, R. L., 1992, Cytokine patterns of immunologically mediated tissue damage, J. Immunol. 149:1470–1475.PubMedGoogle Scholar
  305. Yanuck, M., Carbone, D. P., Pendleton, C. D., Tsukui, T., Winter, S. F., Minna, J. D., and Berzofsky, J. A., 1993, A mutant p53 tumor suppressor protein is a target for peptide-induced CD8+ cytotoxic T cells, Cancer Res. 53:3257–3261.PubMedGoogle Scholar
  306. Yin, X.-M., and Vitetta, E. S., 1992, The lineage relationship between virgin and memory B cells, Int. Immunol. 6:691–698.CrossRefGoogle Scholar
  307. Zangwill, K. M., Stout, R. W., Carlone, G. M., Pais, L., Harekeh, H., Mitchell, S., Wolfe, W. H., Blackwood, V., Plikaytis, B. D., and Wenger, J. D., 1994, Duration of antibody response after meningococcal Polysaccharide vaccination in US Air Force personnel, J. Infect. Dis. 169:847–852.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Mark J. Newman
    • 1
  • Michael F. Powell
    • 2
  1. 1.Vaxcel, Inc.NorcrossUSA
  2. 2.Genentech, Inc.South San FranciscoUSA

Personalised recommendations