1887

Abstract

Vaccine development has played a hugely important role in combating infectious disease. Despite this success, there is still a great need for new vaccines and these are emerging far more slowly than we would wish. Despite the massive expansion in understanding of immune responses to infection, research is often hindered by a lack of understanding of the immune responses required specifically for protection, or by a lack of approved adjuvants and delivery systems to induce the required responses. In addition, the financial commitment required to license new vaccines is significant, and the more lucrative markets are often not those with the greatest need. In this review, we discuss many of the hurdles that new vaccines must overcome in order to reduce morbidity and mortality, and some of the initiatives that are being attempted to supply new vaccines to those that need them most.

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2012-07-01
2019-12-12
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References

  1. Baz Morelli A. , Becher D. , Koernig S. , Silva A. , Drane D. , Maraskovsky E. . ( 2012; ). ISCOMATRIX: a novel adjuvant for use in prophylactic and therapeutic vaccines against infectious diseases. . J Med Microbiol 61:, 935–943. [CrossRef] [PubMed]
    [Google Scholar]
  2. Beernink P. T. , Shaughnessy J. , Braga E. M. , Liu Q. , Rice P. A. , Ram S. , Granoff D. M. . ( 2011; ). A meningococcal factor H binding protein mutant that eliminates factor H binding enhances protective antibody responses to vaccination. . J Immunol 186:, 3606–3614. [CrossRef] [PubMed]
    [Google Scholar]
  3. Butler D. . ( 2011; ). Vaccine campaign to target deadly childhood diarrhoea. . Nature 477:, 519.[CrossRef]
    [Google Scholar]
  4. Corti D. , Voss J. , Gamblin S. J. , Codoni G. , Macagno A. , Jarrossay D. , Vachieri S. G. , Pinna D. , Minola A. . & other authors ( 2011; ). A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. . Science 333:, 850–856. [CrossRef] [PubMed]
    [Google Scholar]
  5. Dannenberg A. M. Jr . ( 2010; ). Perspectives on clinical and preclinical testing of new tuberculosis vaccines. . Clin Microbiol Rev 23:, 781–794. [CrossRef] [PubMed]
    [Google Scholar]
  6. Duewell P. , Kisser U. , Heckelsmiller K. , Hoves S. , Stoitzner P. , Koernig S. , Morelli A. B. , Clausen B. E. , Dauer M. . & other authors ( 2011; ). ISCOMATRIX adjuvant combines immune activation with antigen delivery to dendritic cells in vivo leading to effective cross-priming of CD8+ T cells. . J Immunol 187:, 55–63. [CrossRef] [PubMed]
    [Google Scholar]
  7. Ebensen T. , Guzmán C. A. . ( 2009; ). Immune modulators with defined molecular targets: cornerstone to optimize rational vaccine design. . Adv Exp Med Biol 655:, 171–188. [CrossRef] [PubMed]
    [Google Scholar]
  8. Ekiert D. C. , Bhabha G. , Elsliger M. A. , Friesen R. H. , Jongeneelen M. , Throsby M. , Goudsmit J. , Wilson I. A. . ( 2009; ). Antibody recognition of a highly conserved influenza virus epitope. . Science 324:, 246–251. [CrossRef] [PubMed]
    [Google Scholar]
  9. Ekiert D. C. , Friesen R. H. , Bhabha G. , Kwaks T. , Jongeneelen M. , Yu W. , Ophorst C. , Cox F. , Korse H. J. . & other authors ( 2011; ). A highly conserved neutralizing epitope on group 2 influenza A viruses. . Science 333:, 843–850. [CrossRef] [PubMed]
    [Google Scholar]
  10. Elias D. , Wolday D. , Akuffo H. , Petros B. , Bronner U. , Britton S. . ( 2001; ). Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette-Guérin (BCG) vaccination. . Clin Exp Immunol 123:, 219–225. [CrossRef] [PubMed]
    [Google Scholar]
  11. Enserink M. . ( 2010; ). Global public health. What’s next for disease eradication?. Science 330:, 1736–1739. [CrossRef] [PubMed]
    [Google Scholar]
  12. Ferreira D. M. , Jambo K. C. , Gordon S. B. . ( 2011; ). Experimental human pneumococcal carriage models for vaccine research. . Trends Microbiol 19:, 464–470. [CrossRef] [PubMed]
    [Google Scholar]
  13. GAVI Alliance ( 2011; ). http://www.gavialliance.org/ Date accessed 5 October 2011.
  14. Gibbons D. L. , Spencer J. . ( 2011; ). Mouse and human intestinal immunity: same ballpark, different players; different rules, same score. . Mucosal Immunol 4:, 148–157. [CrossRef] [PubMed]
    [Google Scholar]
  15. Goozner M. . ( 2004; ). The $800 Million Pill: The Truth behind the Cost of New Drugs. Berkeley:: University of California Press;.
    [Google Scholar]
  16. Graham D. Y. , Opekun A. R. , Osato M. S. , El-Zimaity H. M. , Lee C. K. , Yamaoka Y. , Qureshi W. A. , Cadoz M. , Monath T. P. . ( 2004; ). Challenge model for Helicobacter pylori infection in human volunteers. . Gut 53:, 1235–1243. [CrossRef] [PubMed]
    [Google Scholar]
  17. He Y. , Xiang Z. , Mobley H. L. . ( 2010; ). Vaxign: the first web-based vaccine design program for reverse vaccinology and applications for vaccine development. . J Biomed Biotechnol 2010:, 297505. [CrossRef] [PubMed]
    [Google Scholar]
  18. Higgins S. C. , Mills K. H. . ( 2010; ). TLR, NLR agonists, and other immune modulators as infectious disease vaccine adjuvants. . Curr Infect Dis Rep 12:, 4–12. [CrossRef] [PubMed]
    [Google Scholar]
  19. Higgins S. C. , Jarnicki A. G. , Lavelle E. C. , Mills K. H. . ( 2006; ). TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. . J Immunol 177:, 7980–7989.[PubMed] [CrossRef]
    [Google Scholar]
  20. Hotez P. . ( 2011; ). A handful of ‘antipoverty’ vaccines exist for neglected diseases, but the world’s poorest billion people need more. . Health Aff (Millwood) 30:, 1080–1087. [CrossRef] [PubMed]
    [Google Scholar]
  21. Huang H. , Ostroff G. R. , Lee C. K. , Specht C. A. , Levitz S. M. . ( 2010; ). Robust stimulation of humoral and cellular immune responses following vaccination with antigen-loaded β-glucan particles. . mBio 1:, e00164-10.[CrossRef]
    [Google Scholar]
  22. Karlsson E. A. , Sheridan P. A. , Beck M. A. . ( 2010; ). Diet-induced obesity impairs the T cell memory response to influenza virus infection. . J Immunol 184:, 3127–3133.[CrossRef]
    [Google Scholar]
  23. Kaufman D. R. , De Calisto J. , Simmons N. L. , Cruz A. N. , Villablanca E. J. , Mora J. R. , Barouch D. H. . ( 2011; ). Vitamin A deficiency impairs vaccine-elicited gastrointestinal immunity. . J Immunol 187:, 1877–1883. [CrossRef] [PubMed]
    [Google Scholar]
  24. Kool M. , Fierens K. , Lambrecht B. N. . ( 2012; ). Alum adjuvant: some of the tricks of the oldest adjuvant. . J Med Microbiol 61:, 927–934.[PubMed] [CrossRef]
    [Google Scholar]
  25. Light D. W. , Andrus J. K. , Warburton R. N. . ( 2009; ). Estimated research and development costs of rotavirus vaccines. . Vaccine 27:, 6627–6633. [CrossRef] [PubMed]
    [Google Scholar]
  26. Madico G. , Welsch J. A. , Lewis L. A. , McNaughton A. , Perlman D. H. , Costello C. E. , Ngampasutadol J. , Vogel U. , Granoff D. M. , Ram S. . ( 2006; ). The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. . J Immunol 177:, 501–510.[PubMed] [CrossRef]
    [Google Scholar]
  27. Marzetta C. A. , Lee S. S. , Wrobel S. J. , Singh K. J. , Russell N. , Esparza J. . ( 2010; ). The potential global market size and public health value of an HIV-1 vaccine in a complex global market. . Vaccine 28:, 4786–4797. [CrossRef] [PubMed]
    [Google Scholar]
  28. McElligott S. . ( 2009; ). Addressing supply side barriers to introduction of new vaccines to the developing world. . Am J Law Med 35:, 415–441.[PubMed]
    [Google Scholar]
  29. Mestas J. , Hughes C. C. . ( 2004; ). Of mice and not men: differences between mouse and human immunology. . J Immunol 172:, 2731–2738.[PubMed] [CrossRef]
    [Google Scholar]
  30. Minassian A. M. , Ronan E. O. , Poyntz H. , Hill A. V. , McShane H. . ( 2011; ). Preclinical development of an in vivo BCG challenge model for testing candidate TB vaccine efficacy. . PLoS ONE 6:, e19840. [CrossRef] [PubMed]
    [Google Scholar]
  31. Moretto M. M. , Lawlor E. M. , Khan I. A. . ( 2008; ). Aging mice exhibit a functional defect in mucosal dendritic cell response against an intracellular pathogen. . J Immunol 181:, 7977–7984.[PubMed] [CrossRef]
    [Google Scholar]
  32. Moxon E. R. , Siegrist C. A. . ( 2011; ). The next decade of vaccines: societal and scientific challenges. . Lancet 378:, 348–359. [CrossRef] [PubMed]
    [Google Scholar]
  33. Mutsch M. , Zhou W. , Rhodes P. , Bopp M. , Chen R. T. , Linder T. , Spyr C. , Steffen R. . ( 2004; ). Use of the inactivated intranasal influenza vaccine and the risk of Bell’s palsy in Switzerland. . N Engl J Med 350:, 896–903. [CrossRef] [PubMed]
    [Google Scholar]
  34. NHS ( 2010; ). Why aren't children in the UK vaccinated against chickenpox? http://www.nhs.uk/chq/Pages/1032.aspx Date accessed 5 October 2011.
  35. Outterson K. , Kesselheim A. S. . ( 2008; ). Market-based licensing for HPV vaccines in developing countries. . Health Aff (Millwood) 27:, 130–139. [CrossRef] [PubMed]
    [Google Scholar]
  36. Peng S. L. . ( 2005; ). Signaling in B cells via Toll-like receptors. . Curr Opin Immunol 17:, 230–236. [CrossRef] [PubMed]
    [Google Scholar]
  37. PhRMA ( 2010; ). Medicines in Development for Infectious Diseases. http://www.phrma.org/sites/default/files/354/infectious_diseases_2010.pdf Date accessed 4 October 2011.
  38. Plahte J. . ( 2005; ). Tiered pricing of vaccines: a win-win-win situation, not a subsidy. . Lancet Infect Dis 5:, 58–63. [CrossRef] [PubMed]
    [Google Scholar]
  39. Pulendran B. . ( 2009; ). Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology. . Nat Rev Immunol 9:, 741–747.[PubMed]
    [Google Scholar]
  40. Pulendran B. , Ahmed R. . ( 2011; ). Immunological mechanisms of vaccination. . Nat Immunol 12:, 509–517. [CrossRef] [PubMed]
    [Google Scholar]
  41. Rozenbaum M. H. , van Hoek A. J. , Vegter S. , Postma M. J. . ( 2008; ). Cost-effectiveness of varicella vaccination programs: an update of the literature. . Expert Rev Vaccines 7:, 753–782. [CrossRef] [PubMed]
    [Google Scholar]
  42. Rutstein R. M. , Rudy B. , Codispoti C. , Watson B. . ( 1994; ). Response to hepatitis B immunization by infants exposed to HIV. . AIDS 8:, 1281–1284. [CrossRef] [PubMed]
    [Google Scholar]
  43. Salisbury D. , Ramsay M. , Noakes K. . ( 2006; ). Varicella. . In Immunisation Against Infectious Disease, pp. 421–442. London:: The Stationary Office;.
    [Google Scholar]
  44. Sasaki S. , Sullivan M. , Narvaez C. F. , Holmes T. H. , Furman D. , Zheng N. Y. , Nishtala M. , Wrammert J. , Smith K. . & other authors ( 2011; ). Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies. . J Clin Invest 121:, 3109–3119. [CrossRef] [PubMed]
    [Google Scholar]
  45. Sauerwein R. W. , Roestenberg M. , Moorthy V. S. . ( 2011; ). Experimental human challenge infections can accelerate clinical malaria vaccine development. . Nat Rev Immunol 11:, 57–64. [CrossRef] [PubMed]
    [Google Scholar]
  46. Schreibelt G. , Benitez-Ribas D. , Schuurhuis D. , Lambeck A. J. , van Hout-Kuijer M. , Schaft N. , Punt C. J. , Figdor C. G. , Adema G. J. , de Vries I. J. . ( 2010; ). Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells. . Blood 116:, 564–574. [CrossRef] [PubMed]
    [Google Scholar]
  47. Sekaly R. P. . ( 2008; ). The failed HIV Merck vaccine study: a step back or a launching point for future vaccine development?. J Exp Med 205:, 7–12. [CrossRef] [PubMed]
    [Google Scholar]
  48. Sette A. , Rappuoli R. . ( 2010; ). Reverse vaccinology: developing vaccines in the era of genomics. . Immunity 33:, 530–541. [CrossRef] [PubMed]
    [Google Scholar]
  49. Seubert A. , Calabro S. , Santini L. , Galli B. , Genovese A. , Valentini S. , Aprea S. , Colaprico A. , D’Oro U. . & other authors ( 2011; ). Adjuvanticity of the oil-in-water emulsion MF59 is independent of Nlrp3 inflammasome but requires the adaptor protein MyD88. . Proc Natl Acad Sci U S A 108:, 11169–11174. [CrossRef] [PubMed]
    [Google Scholar]
  50. The Global Polio Eradication Initiative ( 2010; ). http://www.polioeradication.org/ Date accessed 5 October 2011.
  51. Thompson K. M. , Tebbens R. J. , Pallansch M. A. , Kew O. M. , Sutter R. W. , Aylward R. B. , Watkins M. , Gary H. E. Jr , Alexander J. . & other authors ( 2008; ). The risks, costs, and benefits of possible future global policies for managing polioviruses. . Am J Public Health 98:, 1322–1330. [CrossRef] [PubMed]
    [Google Scholar]
  52. von Bernuth H. , Picard C. , Jin Z. , Pankla R. , Xiao H. , Ku C. L. , Chrabieh M. , Mustapha I. B. , Ghandil P. . & other authors ( 2008; ). Pyogenic bacterial infections in humans with MyD88 deficiency. . Science 321:, 691–696. [CrossRef] [PubMed]
    [Google Scholar]
  53. WHO ( 2008; ). The Top 10 Causes of Death. Fact Sheet No. 310. http://www.who.int/mediacentre/factsheets/fs310/en/index.html Date accessed 30 September 2011.
  54. WHO ( 2009; ). Childhood vaccines at all-time high, but access not yet equitable. http://www.who.int/mediacentre/news/releases/2009/state_immunizaton_20091021/en/ Date accessed 4 October 2011.
  55. WHO/UNICEF ( 2010; ). Global Immunization Data. http://www.who.int/immunization_monitoring/Global_Immunization_Data.pdf Date accessed 10 August 2011.
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