Advertisement

Virus Glycoproteins Tagged with the Human Fc Domain as Second Generation Vaccine Candidates

  • Silvia Loureiro
  • Elena Robinson
  • Hongying Chen
  • Pongsathon Phapugrangkul
  • Camilo Colaco
  • Ian M JonesEmail author
Chapter

Abstract

Traditional vaccines such as inactivated or live attenuated vaccines, are gradually giving way to more biochemically defined vaccines that are most often based on a recombinant antigen known to possess neutralizing epitopes. Such vaccines can offer improvements in speed, safety and manufacturing process but an inevitable consequence of their high degree of purification is that immunogenicity is reduced through the lack of the innate triggering molecules present in more complex preparations. Targeting recombinant vaccines to antigen presenting cells (APCs) such as dendritic cells however can improve immunogenicity by ensuring that antigen processing is as efficient as possible. Immune complexes, one of a number of routes of APC targeting, are mimicked by a recombinant approach, crystallizable fragment (Fc) fusion proteins, in which the target immunogen is linked directly to an antibody effector domain capable of interaction with receptors, FcR, on the APC cell surface. A number of virus Fc fusion proteins have been expressed in insect cells using the baculovirus expression system and shown to be efficiently produced and purified. Their use for immunization next to non-Fc tagged equivalents shows that they are powerfully immunogenic in the absence of added adjuvant and that immune stimulation is the result of the Fc-FcR interaction.

Keywords

Immune-complexes Crystallizable fragment Fc receptor Glycoprotein tagging Vaccine delivery 

References

  1. Abdel-Motal UM, Guay HM, Wigglesworth K, Welsh RM, Galili U (2007) Immunogenicity of influenza virus vaccine is increased by anti-Gal-mediated targeting to antigen-presenting cells. J Virol 81:9131–9141PubMedCrossRefGoogle Scholar
  2. Abdel-Motal UM, Wigglesworth K, Galili U (2009) Mechanism for increased immunogenicity of vaccines that for in vivo immune complexes with the natural anti-Gal antibody. Vaccine 27:3072–3082PubMedCrossRefGoogle Scholar
  3. Baba TW, Liska V, Hofmann-Lehmann R, Vlasak J, Xu W, Ayehunie S, Cavacini LA, Posner MR, Katinger H, Stiegler G, Bernacky BJ, Rizvi TA, Schmidt R, Hill LR, Keeling ME, Lu Y, Wright JE, Chou TC, Ruprecht RM (2000) Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat Med 6:200–206PubMedCrossRefGoogle Scholar
  4. Balzarini J, Van Laethem K, Hatse S, Vermeire K, De Clercq E, Peumans W, Van Damme E, Vandamme AM, Bölmstedt A, Schols D (2004) Profile of resistance of human immunodeficiency virus to mannose-specific plant lectins. J Virol 78:10617–10627PubMedCrossRefGoogle Scholar
  5. Balzarini J, Van Laethem K, Hatse S, Froeyen M, Van Damme E, Bolmstedt A, Peumans W, De Clercq E, Schols D (2005) Marked depletion of glycosylation sites in HIV-1 gp120 under selection pressure by the mannose-specific plant lectins of Hippeastrum hybrid and Galanthus nivalis. Mol Pharmacol 67:1556–1565PubMedCrossRefGoogle Scholar
  6. Beddows S, Franti M, Dey AK, Kirschner M, Iyer SP, Fisch DC, Ketas T, Yuste E, Desrosiers RC, Klasse PJ, Maddon PJ, Olson WC, Moore JP (2007) A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120. Virology 360:329–340PubMedCrossRefGoogle Scholar
  7. Binley JM, Wrin T, Korber B, Zwick MB, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H, Petropoulos CJ, Burton DR (2004) Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 78:13232–13252PubMedCrossRefGoogle Scholar
  8. Bitsaktsis C, Iglesias BV, Li Y, Colino J, Snapper CM, Hollingshead SK, Pham G, Gosselin DR, Gosselin EJ (2012) Mucosal immunization with an unadjuvanted vaccine that targets Streptococcus pneumoniae PspA to human Fc gamma receptor type I protects against pneumococcal infection through complement- and lactoferrin-mediated bactericidal activity. Infect Immun 80:1166–1180PubMedCrossRefGoogle Scholar
  9. Burton DR, Hessell AJ, Keele BF, Klasse PJ, Ketas TA, Moldt B, Dunlop DC, Poignard P, Doyle LA, Cavacini L, Veazey RS, Moore JP (2011) Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody. Proc Natl Acad Sci USA 108:11181–11186PubMedCrossRefGoogle Scholar
  10. Catasti P, Fontenot JD, Bradbury EM, Gupta G (1995) Local and global structural properties of the HIV-MN V3 loop. J Biol Chem 270:2224–2232PubMedCrossRefGoogle Scholar
  11. Catasti P, Bradbury EM, Gupta G (1996) Structure and polymorphism of HIV-1 third variable loops. J Biol Chem 271:8236–8242PubMedCrossRefGoogle Scholar
  12. Chargelegue D, Drake PM, Obregon P, Prada A, Fairweather N, Ma JK (2005) Highly immunogenic and protective recombinant vaccine candidate expressed in transgenic plants. Infect Immun 73:5915–5922PubMedCrossRefGoogle Scholar
  13. Chen B, Vogan EM, Gong H, Skehel JJ, Wiley DC, Harrison SC (2005) Structure of an unliganded simian immunodeficiency virus gp120 core. Nature 433:834–841PubMedCrossRefGoogle Scholar
  14. Chen H, Xu X, Jones IM (2007) Immunogenicity of the outer domain of a HIV-I clade C gp120. Retrovirology 4:33PubMedCrossRefGoogle Scholar
  15. Chen H, Xu X, Lin HH, Chen SH, Forsman A, Aasa-Chapman M, Jones IM (2008) Mapping the immune response to the outer domain of a human immunodeficiency virus-1 clade C gp120. J Gen Virol 89:2597–2604PubMedCrossRefGoogle Scholar
  16. Corti D, Voss J, Gamblin SJ, Codoni G, Macagno A, Jarrossay D, Vachieri SG, Pinna D, Minola A, Vanzetta F, Silacci C, Fernandez-Rodriguez BM, Agatic G, Bianchi S, Giacchetto-Sasselli I, Calder L, Sallusto F, Collins P, Haire LF, Temperton N, Langedijk JP, Skehel JJ, Lanzavecchia A (2011) A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science 333:850–856PubMedCrossRefGoogle Scholar
  17. Cox MM, Patriarca PA, Treanor J (2008) FluBlok, a recombinant hemagglutinin influenza vaccine. Influenza Other Respir Viruses 2:211–219CrossRefGoogle Scholar
  18. Cross KJ, Burleigh LM, Steinhauer DA (2001) Mechanisms of cell entry by influenza virus. Expert Rev Mol Med 3:1–18PubMedCrossRefGoogle Scholar
  19. Du SX, Xu L, Zhang W, Tang S, Boenig RI, Chen H, Mariano EB, Zwick MB, Parren PW, Burton DR, Wrin T, Petropoulos CJ, Ballantyne JA, Chambers M, Whalen RG (2011) A directed molecular evolution approach to improved immunogenicity of the HIV-1 envelope glycoprotein. PLoS One 6:e20927PubMedCrossRefGoogle Scholar
  20. Durrant LG, Pudney V, Spendlove I, Metheringham RL (2010) Vaccines as early therapeutic interventions for cancer therapy: neutralising the immunosuppressive tumour environment and increasing T cell avidity may lead to improved responses. Expert Opin Biol Ther 10:735–748PubMedCrossRefGoogle Scholar
  21. Ekiert DC, Bhabha G, Elsliger MA, Friesen RH, Jongeneelen M, Throsby M, Goudsmit J, Wilson IA (2009) Antibody recognition of a highly conserved influenza virus epitope. Science 324:246–251PubMedCrossRefGoogle Scholar
  22. Enria DA, Briggiler AM, Sánchez Z (2008) Treatment of Argentine hemorrhagic fever. Antiviral Res 78:132–139PubMedCrossRefGoogle Scholar
  23. Fenouillet E, Barbouche R, Jones IM (2007) Cell entry by enveloped viruses: redox considerations for HIV and SARS-coronavirus. Antioxid Redox Signal 9:1009–1034PubMedCrossRefGoogle Scholar
  24. Fenouillet E, Lavillette D, Loureiro S, Krashias G, Maurin G, Cosset FL, Jones IM, Barbouche R (2008) Contribution of redox status to hepatitis C virus E2 envelope protein function and antigenicity. J Biol Chem 283:26340–26348PubMedCrossRefGoogle Scholar
  25. Haddad EE, Whitfill CE, Avakian AP, Ricks CA, Andrews PD, Thoma JA, Wakenell PS (1997) Efficacy of a novel infectious bursal disease virus immune complex vaccine in broiler chickens. Avian Dis 41:882–889PubMedCrossRefGoogle Scholar
  26. Hu YC, Yao K, Wu TY (2008) Baculovirus as an expression and/or delivery vehicle for vaccine antigens. Expert Rev Vac 7:363–371CrossRefGoogle Scholar
  27. Hung IF, To KK, Lee CK, Lee KL, Chan K, Yan WW, Liu R, Watt CL, Chan WM, Lai KY, Koo CK, Buckley T, Chow FL, Wong KK, Chan HS, Ching CK, Tang BS, Lau CC, Li IW, Liu SH, Chan KH, Lin CK, Yuen KY (2011) Convalescent plasma treatment reduced mortality in patients with severe pandemic influenza A (H1N1) 2009 virus infection. Clin Infect Dis 52:447–456PubMedCrossRefGoogle Scholar
  28. Jefferis R (2010) The antibody paradigm: present and future development as a scaffold for biopharmaceutical drugs. Biotechnol Genet Eng Rev 26:1–42PubMedCrossRefGoogle Scholar
  29. Jeurissen SH, Janse EM, Lehrbach PR, Haddad EE, Avakian A, Whitfill CE (1998) The working mechanism of an immune complex vaccine that protects chickens against infectious bursal disease. Immunology 95:494–500PubMedCrossRefGoogle Scholar
  30. Kang YK, Andjelic S, Binley JM, Crooks ET, Franti M, Iyer SP, Donovan GP, Dey AK, Zhu P, Roux KH, Durso RJ, Parsons TF, Maddon PJ, Moore JP, Olson WC (2009) Structural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1. Vaccine 27:5120–5132PubMedCrossRefGoogle Scholar
  31. Kitabwalla M, Ferrantelli F, Wang T, Chalmers A, Katinger H, Stiegler G, Cavacini LA, Chou TC, Ruprecht RM (2003) Primary African HIV clade A and D isolates: effective cross-clade neutralization with a quadruple combination of human monoclonal antibodies raised against clade B. AIDS Res Hum Retroviruses 19:125–131PubMedCrossRefGoogle Scholar
  32. Konduru K, Bradfute SB, Jacques J, Manangeeswaran M, Nakamura S, Morshed S, Wood SC, Bavari S, Kaplan GG (2011) Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice. Vaccine 29:2968–2977PubMedCrossRefGoogle Scholar
  33. Kong L, Sheppard NC, Stewart-Jones GB, Robson CL, Chen H, Xu X, Krashias G, Bonomelli C, Scanlan CN, Kwong PD, Jeffs SA, Jones IM, Sattentau QJ (2010) Expression-system-dependent modulation of HIV-1 envelope glycoprotein antigenicity and immunogenicity. J Mol Biol 403:131–147PubMedCrossRefGoogle Scholar
  34. Kunkl A, Klaus GG (1981) The generation of memory cells. IV. Immunization with antigen-antibody complexes accelerates the development of B-memory cells, the formation of germinal centres and the maturation of antibody affinity in the secondary response. Immunology 43:371–378PubMedGoogle Scholar
  35. Law M, Cardoso RM, Wilson IA, Burton DR (2007) Antigenic and immunogenic study of membrane proximal external region-grafted gp120 antigens by DNA prime-protein boost immunization strategy. J Virol 81:4272–4285PubMedCrossRefGoogle Scholar
  36. Leopold PL, Wendland RL, Vincent T, Crystal RG (2006) Neutralized adenovirus-immune complexes can mediate effective gene transfer via an Fc receptor-dependent infection pathway. J Virol 80:10237–10247PubMedCrossRefGoogle Scholar
  37. Li Y, Cleveland B, Klots I, Travis B, Richardson BA, Anderson D, Montefiori D, Polacino P, Hu SL (2008) Removal of a single N-linked glycan in human immunodeficiency virus type 1 gp120 results in an enhanced ability to induce neutralizing antibody responses. J Virol 82:638–651PubMedCrossRefGoogle Scholar
  38. Lombard M, Pastoret PP, Moulin AM (2007) A brief history of vaccines and vaccination. Rev Sci Technol 26:29–48Google Scholar
  39. Loureiro S, Ren J, Phapugrangkul P, Colaco CA, Bailey CR, Shelton H, Molesti E, Temperton NJ, Barclay WS, Jones IM (2011) Adjuvant-free immunization with hemagglutinin-Fc fusion proteins as an approach to influenza vaccines. J Virol 85:3010–3014PubMedCrossRefGoogle Scholar
  40. Lu L, Palaniyandi S, Zeng R, Bai Y, Liu X, Wang Y, Pauza CD, Roopenian DC, Zhu X (2011) A neonatal Fc receptor-targeted mucosal vaccine strategy effectively induces HIV-1 antigen-specific immunity to genital infection. J Virol 85:10542–10553PubMedCrossRefGoogle Scholar
  41. Ma JK, Drake PM, Chargelegue D, Obregon P, Prada A (2005) Antibody processing and engineering in plants, and new strategies for vaccine production. Vaccine 23:1814–1818PubMedCrossRefGoogle Scholar
  42. Mathewson AC, Bishop A, Yao Y, Kemp F, Ren J, Chen H, Xu X, Berkhout B, van der Hoek L, Jones IM (2008) Interaction of severe acute respiratory syndrome-coronavirus and NL63 coronavirus spike proteins with angiotensin converting enzyme-2. J Gen Virol 89:2741–2745PubMedCrossRefGoogle Scholar
  43. Metheringham RL, Pudney VA, Gunn B, Towey M, Spendlove I, Durrant LG (2009) Antibodies designed as effective cancer vaccines. MAbs 1:71–85PubMedCrossRefGoogle Scholar
  44. Moore PL, Crooks ET, Porter L, Zhu P, Cayanan CS, Grise H, Corcoran P, Zwick MB, Franti M, Morris L, Roux KH, Burton DR, Binley JM (2006) Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1. J Virol 80:2515–2528PubMedCrossRefGoogle Scholar
  45. Nichol KL, Treanor JJ (2006) Vaccines for seasonal and pandemic influenza. J Infect Dis 194:S111–S118PubMedCrossRefGoogle Scholar
  46. Nicholson KG, Wood JM, Zambon M (2003) Influenza. Lancet 362:1733–1745PubMedCrossRefGoogle Scholar
  47. Obregon P, Chargelegue D, Drake PM, Prada A, Nuttall J, Frigerio L, Ma JK (2006) HIV-1 p24-immunoglobulin fusion molecule: a new strategy for plant-based protein production. Plant Biotechnol J 4:195–207PubMedCrossRefGoogle Scholar
  48. Pantophlet R, Burton DR (2006) GP120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol 24:739–769PubMedCrossRefGoogle Scholar
  49. Paul M, van Dolleweerd C, Drake PM, Reljic R, Thangaraj H, Barbi T, Stylianou E, Pepponi I, Both L, Hehle V, Madeira L, Inchakalody V, Ho S, Guerra T, Ma JK (2011) Molecular pharming: future targets and aspirations. Hum Vac 7:375–382CrossRefGoogle Scholar
  50. Pengelley SC, Chapman DC, Mark Abbott W, Lin HH, Huang W, Dalton K, Jones IM (2006) A suite of parallel vectors for baculovirus expression. Protein Expr Purif 48:173–181PubMedCrossRefGoogle Scholar
  51. Pitisuttithum P, Gilbert P, Gurwith M, Heyward W, Martin M, van Griensven F, Hu D, Tappero JW, Choopanya K, Bangkok Vaccine Evaluation Group (2006) Randomized, double-blind, placebo-controlled efficacy trial of a bivalent recombinant glycoprotein 120 HIV-1 vaccine among injection drug users in Bangkok, Thailand. J Infect Dis 194:1661–1671PubMedCrossRefGoogle Scholar
  52. Pleass RJ (2009) Fc-recptors and immunity to malaria: from models to vaccines. Parasite Immunol 31:529–538PubMedCrossRefGoogle Scholar
  53. Qi Z, Pan C, Lu H, Shui Y, Li L, Li X, Xu X, Liu S, Jiang S (2010) A recombinant mimetics of the HIV-1 gp41 prehairpin fusion intermediate fused with human IgG Fc fragment elicits neutralizing antibody response in the vaccinated mice. Biochem Biophys Res Commun 398:506–512PubMedCrossRefGoogle Scholar
  54. Reagan-Shaw S, Nihal M, Ahmad N (2008) Dose translation from animal to human studies revisited. FASEB J 22:659–661PubMedCrossRefGoogle Scholar
  55. Regnault A, Lankar D, Lacabanne V, Rodriguez A, Théry C, Rescigno M, Saito T, Verbeek S, Bonnerot C, Ricciardi-Castagnoli P, Amigorena S (1999) Fcγ receptor-mediated induction of dendritic cell maturation and major histocompatibility complex class I-restricted antigen presentation after immune complex internalization. J Exp Med 189:371–380PubMedCrossRefGoogle Scholar
  56. Rodenburg CM, Li Y, Trask SA, Chen Y, Decker J, Robertson DL, Kalish ML, Shaw GM, Allen S, Hahn BH, Gao F, UNAIDS and NIAID Networks for HIV Isolation and Characterization (2001) Near full-length clones and reference sequences for subtype C isolates of HIV type 1 from three different continents. AIDS Res Hum Retroviruses 17:161–168PubMedCrossRefGoogle Scholar
  57. Sanders RW, Venturi M, Schiffner L, Kalyanaraman R, Katinger H, Lloyd KO, Kwong PD, Moore JP (2002) The mannose-dependent epitope for neutralizing antibody 2 G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol 76:7293–7305PubMedCrossRefGoogle Scholar
  58. Scanlan CN, Pantophlet R, Wormald MR, Ollmann Saphire E, Stanfield R, Wilson IA, Katinger H, Dwek RA, Rudd PM, Burton DR (2002) The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2 G12 recognizes a cluster of alpha1→2 mannose residues on the outer face of gp120. J Virol 76:7306–7321PubMedCrossRefGoogle Scholar
  59. Schmidt SR (2009) Fusion-proteins as biopharmaceuticals–applications and challenges. Curr Opin Drug Discov Dev 12:284–295Google Scholar
  60. Shelton H, Ayora-Talavera G, Ren J, Loureiro S, Pickles RJ, Barclay WS, Jones IM (2011) Receptor binding profiles of avian influenza virus hemagglutinin subtypes on human cells as a predictor of pandemic potential. J Virol 85:1875–1880PubMedCrossRefGoogle Scholar
  61. Skehel JJ, Wiley DC (2000) Receptor binding and membrane fusion in virus entry: the influenza hemagglutinin. Annu Rev Biochem 69:531–569PubMedCrossRefGoogle Scholar
  62. Su L, Graf M, Zhang Y, von Briesen H, Xing H, Köstler J, Melzl H, Wolf H, Shao Y, Wagner R (2000) Characterization of a virtually full-length human immunodeficiency virus type 1 genome of a prevalent intersubtype (C/B’) recombinant strain in China. J Virol 74:11367–11376PubMedCrossRefGoogle Scholar
  63. Sui J, Hwang WC, Perez S, Wei G, Aird D, Chen LM, Santelli E, Stec B, Cadwell G, Ali M, Wan H, Murakami A, Yammanuru A, Han T, Cox NJ, Bankston LA, Donis RO, Liddington RC, Marasco WA (2009) Structural and functional bases for broad-spectrum neutralization of avian and human influenza A viruses. Nat Struct Mol Biol 16:265–273PubMedCrossRefGoogle Scholar
  64. Treanor J (2009) Recombinant proteins produced in insect cells. Curr Top Microbiol Immunol 333:211–225PubMedCrossRefGoogle Scholar
  65. Treanor JJ, Wilkinson BE, Masseoud F, Hu-Primmer J, Battaglia R, O’Brien D, Wolff M, Rabinovich G, Blackwelder W, Katz JM (2001) Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans. Vaccine 19:1732–1737PubMedCrossRefGoogle Scholar
  66. Treanor JJ, Schiff GM, Couch RB, Cate TR, Brady RC, Hay CM, Wolff M, She D, Cox MM (2006) Dose-related safety and immunogenicity of a trivalent baculovirus-expresse influenza-virus hemagglutinin vaccine in elderly adults. J Infect Dis 193:1223–1228PubMedCrossRefGoogle Scholar
  67. Treanor JJ, Schiff GM, Hayden FG, Brady RC, Hay CM, Meyer AL, Holden-Wiltse J, Liang H, Gilbert A, Cox M (2007) Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial. JAMA 297:1577–1582PubMedCrossRefGoogle Scholar
  68. Tripp RA, Tompkins SM (2008) Recombinant vaccines for influenza. Curr Opin Investig Drugs 9:836–845PubMedGoogle Scholar
  69. van Oers MM, King LA (2011) The application of baculoviruses in human and veterinary medicine: an overview. J Invertebr Pathol 107(Suppl):S1–S2PubMedCrossRefGoogle Scholar
  70. Walker LM, Burton DR (2010) Rational antibody-based HIV-1 vaccine design: current approaches and future directions. Curr Opin Immunol 22:358–366PubMedCrossRefGoogle Scholar
  71. Wei X, Decker JM, Wang S, Hui H, Kappes JC, Wu X, Salazar-Gonzalez JF, Salazar MG, Kilby JM, Saag MS, Komarova NL, Nowak MA, Hahn BH, Kwong PD, Shaw GM (2003) Antibody neutralization and escape by HIV-1. Nature 422:307–312PubMedCrossRefGoogle Scholar
  72. Weldon WC, Wang BZ, Martin MP, Koutsonanos DG, Skountzou I, Compans RW (2010) Enhanced immunogenicity of stabilized trimeric soluble influenza hemagglutinin. PLoS One 5:e12466PubMedCrossRefGoogle Scholar
  73. Wen YM, Qu D, Zhou SH (1999) Antigen-antibody complex as therapeutic vaccine for viral hepatitis B. Int Rev Immunol 18:251–258PubMedCrossRefGoogle Scholar
  74. Wernersson S, Karlsson MC, Dahlström J, Mattsson R, Verbeek JS, Heyman B (1999) IgG-mediated enhancement of antibody responses is low in Fc receptor gamma chain-deficient mice and increased in Fc gamma RII-deficient mice. J Immunol 163:618–622PubMedGoogle Scholar
  75. Yang X, Tomov V, Kurteva S, Wang L, Ren X, Gorny MK, Zolla-Pazner S, Sodroski J (2004) Characterization of the outer domain of the gp120 glycoprotein from human immunodeficiency virus type 1. J Virol 78:12975–12986PubMedCrossRefGoogle Scholar
  76. Yuan W, Bazick J, Sodroski J (2006) Characterization of the multiple conformational states of free monomeric and trimeric human immunodeficiency virus envelope glycoproteins after fixation by cross-linker. J Virol 80:6725–6737PubMedCrossRefGoogle Scholar
  77. Zaharatos GJ, Yu J, Pace C, Song Y, Vasan S, Ho DD, Huang Y (2011) HIV-1 and influenza antigens synthetically linked to IgG2a Fc elicit superior humoral responses compared to unmodified antigens in mice. Vaccine 30:42–50PubMedCrossRefGoogle Scholar
  78. Zhang MY, Wang Y, Mankowski MK, Ptak RG, Dimitrov DS (2009) Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: possible role of the prolonged half-life of the immunogen. Vaccine 27:857–863PubMedCrossRefGoogle Scholar
  79. Zhao Y, Chapman DA, Jones IM (2003) Improving baculovirus recombination. Nucleic Acids Res 31:E6–6PubMedCrossRefGoogle Scholar
  80. Zolla-Pazner S, Cohen SS, Krachmarov C, Wang S, Pinter A, Lu S (2008) Focusing the immune response on the V3 loop, a neutralizing epitope of the HIV-1 gp120 envelope. Virology 372:233–246PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Silvia Loureiro
    • 1
  • Elena Robinson
    • 1
  • Hongying Chen
    • 2
  • Pongsathon Phapugrangkul
    • 1
  • Camilo Colaco
    • 3
  • Ian M Jones
    • 1
    Email author
  1. 1.School of Biological SciencesUniversity of ReadingReadingUK
  2. 2.College of Life SciencesNorthwest A&F UniversityYanglingChina
  3. 3.ImmunoBiology LimitedCambridgeUK

Personalised recommendations