Abstract
The development of vaccines to prevent infectious diseases has been one of the most important contributions of biomedical sciences. Increasing understanding in biochemistry, molecular biology, molecular genetics and related fields have provided an opportunity for the development of new generation vaccines that are based on rational design approaches. This is possible because of proper understanding of the microbial-genetics, biochemistry, host-pathogen interaction and recent developments in molecular immunology. Another important improvement made in the quality of vaccine production is the incorporation of immunomodulators or adjuvants with modified delivery vehicles viz liposomes, Iscoms and microspheres apart from alum being used as a gold standard. This article reviews the art of vaccination from Jenner period to present day context highlighting all the developments made at each stage of the vaccine development. Various criteria have been discussed regarding the selection of epitopes that expand B & T cells, its linkage with other accessory cells of the immune system, means to overcome MHC linked immune unresponsiveness, enhanced antigen processing and presentations that specially induce either helper or cytotoxic or mucosal immune responses were critically discussed.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Jenner E (1798) An Inquiry into the Causes and Effects of the Variolae Vaccinae. (Low, London).
Salk J and Drucker J (1988) Vaccines eds SA. Plotkin and E.A. Mortimer, Ch. 8 158–181 (Philadelphia: W B Saunder).
Melnick JL (1988) Vaccination against poliomyelitis: present possibilities and future prospect. Am J Public Health., 78, 304–305.
Hilleman, MR (1998) Six decades of vaccine development-a personal history. Nat. Med. Vacc. (Suppl). 4, 5.
Kumar P and Rao DN (1993) Strategies for the development of vaccines against malaria; Imunotechnology Biology Education. Oct–Dec; 220–225.
Jason H, Jennifer AH, Bruce WL and Boris RN (2000) Cancer vaccines: an update; In vivo. 14, 571–585.
Wang XY, Kaneko Y, Repasky E and Subjeck JR (2000) Heat shock protein and cancer immunotherapy, Immunol. Invest. 29, 131–137.
Kawakami Y, Nishimura M I, Restifo NP, Topalian SL, Oneil BH, Shilyansky J, Yannelli JR and Rosenberg SA (1993) T-Cell recognition of human melanoma antigens. J. Immunother., 14, 88–93.
Storkus WJ, Zeh HJ, Maeurer MJ, Salter RD and Lotze MT (1993) Identification of human melanoma peptides recognised by class I restricted tumor infiltrating T lymphocytes. J. Immunol., 151, 3719–3727.
Rammensee HG, Friede T and Stevanoviie S (1995) MHC Ligands and peptide motifs: first listing. Immunogenetics, 41, 178–228.
Thomas M, Shinnick J,Gregor Sutcliffe, Nicola Green and Richard A Lerner (1983) Synthetic peptide immunogens as vaccines. Ann. Rev. Microbiol., 37, 425–446.
Sabhnani L and Rao DN (2000) Identification of immunodominant epitope of F1 antigen of Yersinia pestis. FEMS Immunol Med Microbiol. 27, 155–162.
Yoshida A, Nakano Y, Yamashita Y, Oho T, Ito H, Kondo M, Ohishi M and Kooga T (2001) Immunodominant region of Actinobacillus actinomycetemcomitans 40 kilodalton heat shock proteins in patients with Rheumatoid Arthritis. J. Dent. Res. 80, 346–350.
Rodriguez MJ, Sarraseca J, Fominaya J, Cortes E, Sanz A and Casal JI (2001) Identification of an immunodominant epitope in the C terminus of glycoprotein 5 of porcine reproductive and respiratory syndrome virus. J Gen Virol., 82, 995–999.
Ritu G and Rao DN (1992) construction of synthetic immunogens: Use of T-and B-cell epitopes of CS and RESA proteins of Plasmodium falciparum. Vaccine, 10, 761–765.
Sabhnani L, Manocha M, Sridevi K, Shashikiran D, Rayanade R and Rao DN (2003) Developing subunit immunogens using B and T cell epitopes and their constructs derived from the F1 antigen of Yersinis pestis using novel delivery vehicles. FEMS Immunol and Med. Microbiol. 38, 215–229.
Anderer FA and Schlumberger HD (1966) Cross-reactions of antisera against the terminal amino acid and dipeptide of tobacco mosaic virus. Biochem Biophys Acta,.115, 222–224.
Deber CM, Hruby VJ and Kopple KD (eds) (1985) Peptides: Structure and function. (Rockford:PierceChemical Co.) 23p.
Jemmerson R and Peterson Y (1986) Mapping epitopes on a protein antigen by the proteolysis of antigen-antibody complex. Science, 232, 1001–1004.
Shirai M, Pendleton CD, Ahlers J, Takeshita T, Newman M and Berzofsky JA (1994) Herper-CTL determinant linkage required for priming of anti HIV CD8+CTL in vivo with peptide vaccine constructs. J. Immunol. 152, 549–556.
Manzar KJ and Rao DN (1991) Antibodies to P. falciparum Ring Infected Erythrocyte Surface Antigen and R falciparum and P.vivax CS protein. Med. Sci. Res. 19, 345–349.
Manocha M, Sridevi K, Tomar D, Chitralekha KT and Rao DN (2002) Synthetic peptides as Immunoprophylaxis and immunotherapeutics. Proc. Indian Natn Sci. Acad. B68 No. 1, 29–46.
Frangione-Beebe M, Albrecht B, Dakappagari N, Rose RT, Brooks CL, Schwendeman SP, Laimore MD and Kaumaya PT (2000) Enhanced immunogenicity of a conformational epitope of human T-lymphotropic virus type 1 using a novel chimeric peptide. Vaccine, 19, 1068–1081.
Wilson ZA, Ladner RC, Skehel JJ and Wiley DC (1983) The structure and role of the carbohydrate moieties of influenza virus haemagglutinin. Biochem Soc Trans. 11, 145–147.
Rowlands DJ, Clarke BE, Caroll AR (1983) Chemical basis of antigenic variation in foot and mouth disease virus. Nature, 306, 694–697.
Dressman GR, Sanchez Y and Ionescu-Matiu (1982) Antibody to hepatitis B surface antigen after a single inoculation of uncoupled synthetic HbsAg peptides. Nature, 295, 158–160.
Neurath AR, Seto B and Strick N (1989) Antibodies to synthetic peptides from the pre-SI region of hepatitis B virus envelope protein are virus neutralizing and protective. Vaccine, 7, 234–236.
Margalit H, Spouge JL, Cornette JL, Cease KB, Delisi C and Berzofsky J A (1987) Prediction of Immunodominant helper T cell antigenic sites from the primary sequence. J. Immunol. 138, 2213–2229.
Hammer J, Bono E, Gallazi F, Beunis SC, Nagy Z, Sinigaglia F (1994) Precise predictions of Major histocompatibility complex Class II peptide interaction, based on peptide side scanning. J. Exp. Med. 180, 23–53.
Alexander J, Flixes J, Hoffman S, Franke E, Sacci J, Appella E, Chisari FV, Guidotti LG, Chestnut RW, Livingstone B, Sette A (1998) The optimization of helper T lymphocytes (HTL). Function in vaccine development. Immunological Res. 1812, 79–92.
Rosa DS, Tzelepis F, Cunha NG, Soares IS and Roudrigues MM (2004) The pan HLA DR-binding epitope improves adjuvant-assisted immunization with a recombinant protein containing a malaria vaccine candidate. Immunol. Lett. 92, 259–268.
Boehncke WH, Takeshita T, Pendleton CD, Houghten RA, Nasseri SS, Racioppi L, Berzofsky JA and Germain RN (1993) The importance of Dominant Negative effects of amino acid side chain substitution in peptide-MHC molecule interactions and T cells recognition. J. Immunol. 150, 331–341.
Takahashi H, Nakagawa Y, Charles PD, Houghton RA, Yokomura K, Germain RN, and Berzofsky JA (1992) Induction of broadly Cross-Reactive cytotoxic T cells recognizing an HIV-1 envelope determinant. Science, 255, 333–336.
Johansson M and Lovgren-Bengtsson K (1999) Iscoms with different quillaja saponin components differ in their immunomodulating activities. Vaccine, 17, 2894–2900.
Johansen P, Estevez F, Zurbriggen R, Merkle HP, Gluck R, Corradin G, Gander B (2000) Towards clinical testing of a single-administration tetanus vaccine based on PLA/PLGA microspheres. Vaccine, 19, 1047–1050.
Gokulan K, Sangeeta K and Rao DN (1999) Increase in the immunogenicity of HIV peptide antigens by chemical linkage to polytuftsin (TK PR40). DNA and Cell Biology, 18, 623–630.
Gokulan K, Sangeeta K and Rao DN (1997) Bioactive fragments of Human IL-1å[163–171] modulates the immune response to synthetic peptides of HIV. Microbiol. Immunol. 41, 965–974.
Agrawal L, Haq W, Hanson CV, Duzgunes N and Rao DN (2003) Generating neutralizing antibodies, Th1 response and MHC nonrestricted immunogenicity of HIV-1 env and gag peptides in liposomes and ISCOMs with inbuilt adjuvanticity. J. Immunebased therapies and vaccines, 1, 1–22.
Thomas BE, Manocha M, Haq W, Adak T, Pillai CR and Rao DN (2001) Modulation of humoral response to repeat and nonrepeat sequences of CS protein with novel adjuvant and delivery system(s). Ann. Trop. Med. Parasitol. 95, 451–472.
Bhavna C, Kumar P, Haq W, Sabhnani L and Rao DN (1998) Influence of Immunoadjuvants and promiscuous T cell determinants on the Immunogenicity of RESA peptide antigen of P. falciparum. Int. J. Immunopharmac. 20, 259–273.
Kumar P, Biswas S and Rao DN (1998) Potentiation of immune response against RESA peptides of P. falciparum by incorporating universal T-cell epitope CS T3 and immuno potentiator (polytuftsin) and delivery through liposome. Microbiol. Immun. 43, 561–566.
Kumar P and Rao DN (1999) Correlation of T cell response and lymphokine profile with RESA peptides of P. falciparum containing a universal T-cell epitope and an immunopotentiator, polytuftsin. Microbiol. Immunol. 43, 567–576.
Thomas BE, Sridevi K, Haq W and Rao DN (2001) Inducing cell mediated immune response against peptide antigens of circumsporozoite protein of P. vivax. Ann. Trop. Med. Parasitol. 95, 573–586.
Berzofsky JA (1991) Approaches and issues in the development of vaccines against HIV. J. Acquired. Immune. Defic. Syndr. 4, 451–459.
Berzofsky JA (1991) Development of artificial vaccines against HIV using defined epitopes. FASEB J. 5, 2412–2418.
Cease KB and Berzofsky JA (1994) Towards vaccine for AIDS: The emergence of immunobiology-based vaccine development. Annu. Rev. Immunol. 12, 923–989.
Rupert J, Sidney J, Celis E, Kubo RT, Grey HM and Sette A (1993) Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecule. Cell, 74, 929–937.
Schulz M, Zinkernagel RM and Hengartner H (1991) Peptide induced antiviral protection by cytotoxic T cells. Proc. Natl. Acad. Sci. USA. 88, 991–993.
Minev BR, McFarland BJ, Spiess PJ, Rosenberg SA and Restifo NP (1994) Initial signal sequence fused to minimal peptide elicits specific CD8+T-cell responses and prolongs the survival of thymoma-bearing mice. Cancer Res. 41, 55–61.
Marchand M, Weynants P, Rankin E, Arienti F, Belli F, Parmiani G, Cascinelli N, Urlond A, Vanwijck R and Humblet Y (1995) Tumor regression responses in melanoma patients treated with a peptide encoded by gene MAGE-3 (letter). Int. J. Cancer, 63, 883–885.
Salgaller ML, Afsher A, Marincola FM, Rivoltini L, Kawakami Y, and Rosenberg SA (1995) Recognition of multiple epitopes in the human melanoma antigen gp 100 by peripheral blood lymphocytes stimulated in vitro with synthetic peptides. Cancer Res. 55, 4972–4979.
Jaeger E (1996) Generation of cytotoxic T-cell responses with synthetic melanoma associated peptides in vivo with implications for tumor vaccines with melanoma associated antigens. Int. J Cancer. 66, 162–169.
Parkhurst MR, Salgaller ML, Southwood S, Robbins PF, Sette A, Rosenberg SA and Kawakami Y (1996) Improved induction of melanoma reactive CTL with peptides from the melanoma antigen gp100 modified at HLA-A*0201-binding residues. J. Immunol. 157, 2539–2548.
Meidenbaur N, Harris DT, Spitler LF and Whiteside TL (2000) Generation of PSA reactive effector cells after vaccination with PSA-based vaccine in patients with prostate cancer. Prostate, 43, 88–100.
Pinilla C, Martin R, Gran B, Appel JR, Boggiano C, Wilson D, Bane Y and Houghten RA (1999) Exploring Immunological specificity using synthetic peptide combinatorial libraries. Curr. Opin. Immunol. 11, 193–202.
Virgil EJ Schijns (1999) Immunological concepts of vaccine adjuvant activity. Curr. Opinion in Immunol. 12, 456–463.
Janeway CA Jr (1989) Approaching the asymptote? Evolution and revolution in immunology. Cold Spring Harbor Symp Quant Biol. 54, 1–13.
Gupta RK, Relyveld ED, Lindblad EB, Bizzini B, Ben-Efraim S and Gupta CK (1993) Adjuvants—a balance between toxicity and adjuvanticity. Vaccine 11, 293–306.
Ramon G (1924) Sur la toxine et sur li anatoxine diptheriques. Ann InstPasteur. 38, 1–10.
Virgil EJ Schijns (1999) Immunological concepts of vaccine adjuvant activity. Curr. Opinion in Immunol. 12, 456–463.
Derek T and O’Hagan (1997) Recent advances in vaccine adjuvants for systemic and mucosal administration. J. Pharm. 49, 1–10.
Chopra N, Thomas BE, Sabhnani L and Rao DN (2000) Inducing protective antibodies against RESA peptide using modified delivery systems “ISCOMs”. Med. Microbiol. Immunol. 18, 975–83.
Weidner J (2001) Adjuvancy enhancement by modulated release from microspheres. Drug Discov Today 6, 106.
Sridevi K, Manocha M, Sabhnani L, Thomas BE, Rao DN (2000) New age adjuvants and delivery systems for subunit vaccines. Ind. J. Clin. Biochem. 15, 83–100.
Mestecky J, Moldoveanu Z, Michalek SM, Morrow C, Compans RW, Schafer DP and Rusell MW (1996) Current options for vaccine delivery systems by mucosal routes. J. Control. Rel. 34, 567–572.
Gozales C, Home D, Noriega FR, Tacket CO, Davis JR, Losonsky G, Nataro JP, Hofmann A and Levine MM (1994) Salmonella typhi vaccine strain CVD908 expressing these circumsporozoite proteins of Plasmodium falciparum: Strain construction and safety immunogenicity in humans. J. infect. Dis. 169, 927–931.
Manocha M, Pal PC, Chitralekha KT, Thomas BE, Siddhartha DG, Paranjape R, and Kulakmi S and Rao DN (2005) Enhanced mucosal and systemic immune response with intranasal immunization of mice with peptides entrapped in PLGA microparticles in combination with Ulex Europeaus-1 as compared to oral, rectal, or parenteral immunization (manuscript accepted in FEMS Immunol. and Microbiol).
Stittelaar KJ, Boes J, Kersten GF, Spiekstra A, Mulder PG, de Vries P, Roholl PJ, Dalsgaard K, van den Dobbelsteen G, van Alphen L and Osterhaus AD (2000) In vivo antibody response and in vitro CTL activation induced by selected measles candidates, prepared with purified Quil A components. Vaccine, 18, 2482–2493.
Baca-Estrada ME, Foldvari MM, Snider MM, Harding KK, Kournikakis BB, Babiuk LA and Griebel PP (2000) Intranasal immunization with liposome-formulated Yersinia pestis vaccine enhances mucosal immune responses. Vaccine, 18, 2203–2211.
Burton KW, Shameem M, Thanoo BC and DeLuca PP (2000) Extended release peptide delivery systems through the use of PLGA microsphere combinations. J. Biomater. Sci. Polym. Ed. 11, 715–729.
Butler JE, Satam M and Ekstrand JE (1990) Fluoride: an adjuvant for mucosal and systemic immunity. Immunology letters 26, 217–220.
Tengerdy RP and Lacetera NG (1991) Vitamin E adjuvant formulations in mice. Vaccine, 9, 204–206.
Kaur J and Rao DN (1990) New approaches to molecular vaccines. Natl. Med. J. Ind. 3, 58–63.
Jerne NK (1974) Towards a network theory of the immune system. Ann. Inst. Pasteur Immunol. 125C, 373–389.
Sege K and Peterson PA (1978) Use of anti-idiotypic antibodies as cell-surface receptor probes. Proc Natl Acad Sci USA. 75, 2443–2447.
Gilboa E, Smita NK and Kim HL (1998) Immunotherapy of cancer with dendritic-cell based vaccines. Cancer Immunol. Immunother. 46, 82–87.
Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9, 271–296.
Porgador A and Gilboa E (1995) Bone marrow-generated dendritic cells pulsed with a class I—restricted peptide are potent inducers of cytotoxic T lymphocytes. J. Exp. Med. 182, 255–260.
Zitvogel L, Robbins PD, Strokus WJ, Clarke MR, Maeurer MJ, Campbell RL, Davis CG, Tahara H, Schreiber RD and Lotze MT (1996) Interleukin-12 and B7.1 co-stimulation co-operate in the induction of effective antitumour immunity and therapy of established tumours. Eur. J. Immunol. 26, 1335–1341.
Kapusta J, Modelska A, Figlerowicz M, Pniewski T, Letellier M, Lisowa O, Yusibov V, Koprowski H, Plucienniczak A and Legocki AB (1999) A plant-derived edible vaccine against hepatitis B virus. FASEB J. 13, 1796–1799.
Ronald WE (1999) Development of combination vaccines. Vaccine, 17, 1635–1642.
Wolff JA, Dowty ME, Jiao S, Repetto G, Berg RK, Ludtke JJ, Williams P and Slautterback DB (1992) Expression of naked plasms by cultured myotubes and entry of plasmids into T tubules and caveolae of mammalian skeletal muscle. J Cell Sci. 103, 1249–1259.
Li Z (1997) Priming of T cells by heat shock protein-peptide complexes as the basis of tumor vaccines. Semin. Immunol. 9, 315–322.
Yedavelli SPK, Guo L, Daou ME, Srivastava PK, Mittelman A and Tiwari RK (1999) Preventive and therapeutic effect of tumour derived heat shock protein gp96 in an experimental prostate cancer model. Int. J. Molec. Med. 4, 243–248.
Chen CH, Wang TL, Hung CF, Yang Y, Young RA, Pardoll DM and Wu TC (2000) Enhancement of DNA vaccine potency by linkage of antigen gene to an HSP70 gene. Cancer Res. 60, 1035–1042.
Liu DW, Tsao YP, Kung JT, Ding YA, Sytwu HK, Xiao X and Chen SL. (2000) Recombinant adenoassociated virus expressing human papillomavirus type 16 E7 peptide DNA fused with heat shock protein DNA as a potential vaccine for cervical cancer. J. Virology. 74, 2888–2894.
Goldsmith GZ and Dhanasekaran N. (2004) The microrevolution: Applications and impacts of microarray technology on molecular biology and medicine (Review). Int. J. Mol. Med. 13, 483–495.
Kuhn E. (2001) From Library screening to microarray technology: Strategies to determine gene expression profiles and to identify differentially regulated genes in plants. Annals of Botany. 87, 139–155.
Neuman de Vegvar HE. (2004) Microarray profiling of antiviral antibodies form the development of diagnostics, vaccines and therapeutics. Clin. Immunol. 111, 196–201.
Vordermeir HM, Cockle PJ, Whelan AO, Rhodes S and Hewinson RG (2000) Toward the development of diagnostic assays to discriminate between mycobacterium bovis infection and Bacilli Calmette Guerin vaccination in cattle. Clin. Infec. Dis. 30, 291–8.
Wang XY, Kaneko Y, Repasky E and Subjeck JR (2000) Heat shock protein and cancer immunotherapy. Immunol. Invest. 29, 131–137.
Akdis CA and Blaser K (2000) Regulation of specific immune response by chemical and structural modifications of allergens. Int. Arch. Allergy, Immunol. 121, 261–269.
Masihi KN (2000) Immunomodulatory agents for prophylaxis and therapy of infections. Int. J Antimicrob Agents. 14, 181–191.
Roggero MA, Weilenmann C, Bonelo A, Audran R, Renggli J, Spertini F, Corradin G and Lopez J (1999) Plasmodium falciparum Cs C-terminal fragment: preclinical evaluation and phase I clinical studies. Parasitologia, 14, 421–424.
Nardin E, Zavala F, Nussenzweig V and Nussenzweig RS (1999) Pre-erythrocytic malaria vaccine: mechanisms of protective immunity and human vaccine trials. Parasitologia, 41, 397–402.
Sela M (1999) Specific vaccines against autoimmune diseases. C R Acad Sci III. 11933–938.
Poalazzi CC, Perez O and De Filippo J (1999) Rabies vaccine. Developments employing molecular biology methods. Mol Biotechnol. 11, 137–147.
Yusibov V, Shivprasad S, Turpen TH, Dawson W and Koprowski H (1999) Plant viral vectors based on tobamoviruses. Curr Top Microbiol. immunol. 240, 81–94.
Singh M, Das SK, Suri S, Singh O, Talwar GP (1998) Regain of fertility and normality of progeny born during below protective threshold antibody titers in women immunized with the HSD-hCG vaccine. Am. J. Reprod. Immunol. 39, 395–398.
Gupta SK, Jethanandani P, Afzalpurkar A, Kaul R and Santhanam R (1997) Prospects of zona pellucida glycoproteins as immunogens for contraceptive vaccine. Hum. Reprod. Update, 3, 299–300.
Naz RK (2000) Fertilization-related sperm antigens and their immunocontraceptive potentials. Am. J. Reprod. Immunol. 44, 41–46.
Toes RE, Offringa R, Blom RJ, Melief CJ and Kast WM (1996) Peptide vaccination can lead to enhanced tumor growth through specific T-cell tolerance induction. Proc. Natl. Acad. Sci. USA. 93, 7855–7860.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Tomar, D., Chattree, V., Tripathi, V. et al. New dimensions in vaccinology: A new insight. Indian J Clin Biochem 20, 213–230 (2005). https://doi.org/10.1007/BF02893073
Issue Date:
DOI: https://doi.org/10.1007/BF02893073