HIV Vaccines

  • Dani P. Bolognesi


The spread of HIV-1 infection that exploded on the scene in the 1980s continues in pandemic proportions and is having a major impact on public health worldwide. Although the rate of new infections in some parts of the world such as North America and Europe has stabilized, it is rising dramatically in parts of Asia, Latin America, and Africa. An effective prophylactic vaccine that can protect HIV-exposed individuals from infection and disease offers the best hope for combating this pandemic and is a global public health priority. More than 10 years has passed since the identification of HIV-1 as the cause of AIDS and despite intensive research, a path toward a vaccine remains cluttered with obstacles, disappointments, and knowledge gaps. Much of this dilemma stems from the unique features of the virus, particularly its genomic diversification, its multiple routes of infection, and its mechanisms of pathogenesis.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Human Immunodeficiency Virus Infection Simian Immunodeficiency Virus Primary Isolate 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agy, M. B., Frumkin, L. R., Corey, L., Coombs, R. W., Wolinsky, S. M., Koehler, J., Morton, W. R., and Katz, M. G., 1992, Infection of Macaca nemestrina by human immunodeficiency virus type-1, Science 257:103–106.PubMedCrossRefGoogle Scholar
  2. Albert, J., Gaines, H., Sonnerborg, A., Nystrom, G., Pehrson, P. O., Chiodi, F., von Sydow, M., Moberg, L., Lidman, K., and Christensson, B., 1987, Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection, J. Med. Virol 23:13–61.CrossRefGoogle Scholar
  3. Albert, J., Abrahamsson, B., Nagy, K., Aurelius, E., Gaines, H., Nystrom, G., and Fenyo, E. M., 1990, Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera, AIDS 4:107–112.PubMedCrossRefGoogle Scholar
  4. Barnett, S. W., Murthy, K. M., Herndier, B. G., and Levy, J. A., 1995, An AIDS-like condition is induced in baboons by HIV-2, Science 266:642–646.CrossRefGoogle Scholar
  5. Belshe, R. B., Clements, M. L., and Dolin, R., 1993, Safety and immunogenicity of a fully glycosylated recombinant gp160 HIV-1 vaccine in low risk volunteers, J. Infect. Dis. 168:1387–1395.PubMedCrossRefGoogle Scholar
  6. Belshe, R. B., Graham, B. S., and Keefer, M. C., 1994, Neutralizing antibody to HIV-1 in seronegative volunteers immunized with recombinant gp120 from the MN strain of HIV-1, J. Am. Med. Assoc. 272:475–480.CrossRefGoogle Scholar
  7. Berman, P. W., Gregory, T. J., Riddle, L., Nakamure, 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 glycoprotein gp120 but not gp160, Nature 345:622.PubMedCrossRefGoogle Scholar
  8. Berman, P. W., Murthy, K. K., Wrin, T., Vennari, J. C., Cobb, E. K., Eastman, D. J., Champe, M., Nakamura, G. R., Davison, D., Powell, M. F., Bussiere, J., Francis, D. P., Mathews, T., Gregory, T. J., and Obijeski, J. F., 1996, Protection of MN-rgp120-immunized chimpanzees from heterologous infection with a primary isolate of human immunodeficiency virus type 1, J. Infect. Dis. 173:52–59.PubMedCrossRefGoogle Scholar
  9. Burton, D. R., Pyati, J., Koduri, R., Thornton, G. B., Sawyer, L. S. W., Hendry, R. M., Dunlop, N., Nara, P. L., Lamacchia, M., Garratty, E., Stiehm, E. R., Bryson, Y. J., Moore, J. P., Ho, D. D., and Barbas, C. F., III, 1994, Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody, Science 266:1024–1027.PubMedCrossRefGoogle Scholar
  10. Clark, S. J., Saag, M. S. Decker, W. D., Campbell-Hill, S., Roberson, J. L., Veldkamp, P. J., Kappes, J. C., Hahn, B. H., and Shaw, G. M., 1991, High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection, N. Engl. J. Med. 324:954–960.PubMedCrossRefGoogle Scholar
  11. Cooney, E. L., McElrath, M. J., Corey, L., Ju, S.-L., Collier, A. C., Arditti, D., Hoffman, M., Coombs, R. W., Smith, G. E., and Greenberg, P. D., 1993, Enhanced immunity to human immunodeficiency virus (HIV) envelope elicited by a combined vaccine regimen consisting of priming with a vaccinia recombinant expressing HIV envelope and boosting with gp160 protein, Proc. Natl. Acad. Sci. USA 90:1882.PubMedCrossRefGoogle Scholar
  12. Daar, E. S., Li, X. L., Moudgil, T., and Ho, D. D., 1990, High concentrations of recombinant soluble CD4 are required to neutralize primary human immunodeficiency virus type 1 isolates, Proc. Natl. Acad. Sci. USA 87:6674.CrossRefGoogle Scholar
  13. Daar, E. S., Moudgil, T., Meyer, R. D., and Ho, D. D., 1991, Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection, N. Engl. J. Med. 324:961–964.PubMedCrossRefGoogle Scholar
  14. Daniel, M. D., Kirchhoff, F., Czajak, S. C., Sehgal, P. K., and Desrosiers, R. C., 1992, Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene, Science 258:1938.PubMedCrossRefGoogle Scholar
  15. Egan, M. A., Pavlat, W. A., Tartaglia, J., Paoletti, E., Weinhold, K. J., Clements, M. L., and Siliciano, R. F., 1995, Induction of human immunodeficiency virus type 1 (HIV-1)-specific cytolytic T lymphocyte responses in seronegative adults by a nonreplication, host-range-restricted canarypox vector (ALVAC) carrying the HIV-MN env gene, J. Infect. Dis. 171:1623–1627.PubMedCrossRefGoogle Scholar
  16. El-Amad, Z., Murthy, K. K., Higgins, K., Cobb, E. K., Haigwood, N. L., Levy, J. A., and Steimer, K. S., 1996, Resistance of chimpanzees immunized with recombinant gp120SF2 to challenge by HIV-1SF2, AIDS 1995, 9:1313–1322.Google Scholar
  17. Embretson, J., Zupancic, M., Ribas, J. L., Burke, A., Racz, P., Tenner-Racz, K., and Haase, A. T., 1993, Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS, Nature 362:359–362.PubMedCrossRefGoogle Scholar
  18. Emini, E. A., Nara, P. L., and Scheif, W. A., 1990, Antibody-mediated in vitro neutralization of human immunodeficiency virus type 1 abolished infectivity for chimpanzees, J. Virol. 64:3674–3678.PubMedGoogle Scholar
  19. Emini, E. A., Schleif, W. A., Nunberg, J. H., Conley, A. J., Eda, Y., Tokiyoshi, S., Putney, S. D., Matsushita, S., Cobb, K. E., Jett, C. M., Eichberg, J. W., and Murthy, K. K., 1992, Prevention of HIV-1 infection in chimpanzees by gp120 V3 domain-specific monoclonal antibody, Nature 355:728.PubMedCrossRefGoogle Scholar
  20. Fauci, A. S., 1993, Multifactorial nature of human immunodeficiency virus disease: Implications for therapy, Science 262:1011–1018.PubMedCrossRefGoogle Scholar
  21. Ferbas, J., Kaplan, A. H., Hausner, M. A., Hultin, L. E., Matud, J. L., Liu, Z., Panicali, D. L., Nerng-Ho, H., Detels, R., and Giorgi, J. V., 1995, Virus burden in long-term survivors of human immunodeficiency virus (HIV) infection is a determinant of anti-HIV CD8+ lymphocyte activity, J. Infect. Dis. 172:329–339.PubMedCrossRefGoogle Scholar
  22. Girard, M. P., and Eichberg, J. W., 1990, Progress in the development of SIV vaccines, AIDS 4:S143.PubMedCrossRefGoogle Scholar
  23. Girard, M., Kieny, M. P., Pinter, A., Barre-Sinoussi, F., Nara, P., Kolbe, H., Kusumi, K., Chaput, A., Reinhart, T., and Muchmore, E., 1991, Immunization of chimpanzees confers protection against challenge with human immunodeficiency virus, Proc. Natl. Acad. Sci. USA 88:542.PubMedCrossRefGoogle Scholar
  24. Gomez, M. P., and Hildreth, J. E. K., 1995, Antibody to adhesion molecule LFA-1 enhances plasma neutralization of HIV-1, J. Virol. 69:4628–4632.PubMedGoogle Scholar
  25. Graham, B. S., Matthews, T. J., and Belshe, R. B., 1993, augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinianaive adults. The NIAID AIDS Vaccine Clinical Trials Network, J. Infect. Dis. 167:533–537.PubMedCrossRefGoogle Scholar
  26. Hanson, C. V., 1994, Measuring vaccine-induced HIV neutralization: Report of a workshop, AIDS Res. Hum. Retrovir. 10:645–648.PubMedCrossRefGoogle Scholar
  27. Hirsch, V M., Goldstein, S., Elkins, W. R., London, W. T., Zack, P. M., Montefiori, D. C., and Johnson, P. R., 1994, Prolonged clinical latency and survival of macaques given a whole inactivated simian immunodeficiency virus vaccine, J. Infect. Dis. 170:51–59.PubMedCrossRefGoogle Scholar
  28. Ho, D. D., 1995, Time to hit HIV, early and hard, N. Engl. J. Med. 333:450–451.PubMedCrossRefGoogle Scholar
  29. Hoff, R., and Lawrence, D. N., 1996, Preparation for vaccine trials, in: Development and Applications of Vaccines and Gene Therapy in AIDS Antibiotics and Chemotherapy, Volume 48 (G. Giraldo, ed.) S. Karger A.G., Basel, Switzerland.Google Scholar
  30. Israel, Z. R., Edmonson, P. E., Maul, D. H., O’Neil, S. P., Mossman, S. P., Thiriart, C., Fabry, L., van Opstal, O., Bruck, C., Bex, F., Burny, A., Fultz, P. N., Mullins, J. I., and Hoover, E. A., 1994, Incomplete protection, but suppression of virus burden, elicited by subunit simian immunodeficiency virus vaccines, J. Virol. 68:1843–1853.PubMedGoogle Scholar
  31. Koup, R. A., Safrit, J. T., Cao, Y., Andrews, C. A., McLeod, G., Borkowsky, W., Farthing, C., and Ho, D. D., 1994, Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type I syndrome, J. Virol. 68:4650–4655.PubMedGoogle Scholar
  32. Li, J., Lord, C. I., Haseltine, W., Letvin, N. L., and Sodroski, J., 1992, Infection of cynomolgus macaques with a chimeric HIV-1/SIV mac virus that expresses the HIV-1 envelope glycoprotein, J. Acq. Immune Defic. Syndr. 5:639–646.Google Scholar
  33. Loes, S. K. L., Hirschell, B. J., Hoen, B., and Cooper, D. A., 1995, A controlled trial of zidovudine in primary human immunodeficiency virus infection, N. Engl. J. Med. 333:408.CrossRefGoogle Scholar
  34. McClure, J., Scheibel, M., Anderson, D., Steele, J., Misher, L., Morton, W., and Hu, S.-L., 1994, Pathogenicity and infectivity of HIV-1 in macaques, in: Abstract Book Volume 1, Tenth International Conference on STB, Yokohama, Japan, p. 60, Abstract #193A.Google Scholar
  35. McCune, J. M., Namikawa, R., Kaneshima, H., Shultz, L. D., Lieberman, M., and Weissman, I. L., 1988, The SCID-hu mouse: Murine model for the analysis of human hematolymphoid differentiation and function, Science 241:1632–1639.PubMedCrossRefGoogle Scholar
  36. McElrath, M. J., Corey, L., Clements, M. L., Belshe, R., Keefer, M., Graham, B., Fast, P., Matthews, T., Duliege, A. M., Francis, D., and the NIAID AVEG, 1994, A phase II HIV vaccine trial in seronegative subjects: Safety, immunogenicity and future direction, in: Abstract Book Volume 1, Tenth International Conference on STB, Yokohama, Japan, p. 91, Abstract #317A.Google Scholar
  37. Matthews, T. J., 1994, Dilemma of neutralization resistance of HIV-1 field isolates and vaccine development, AIDS Res. Hum. Retrovir. 10:631–632.PubMedCrossRefGoogle Scholar
  38. Mellors, J. W., Kingsley, L. A., Rinaldo, C. R., Todd, J. A., Hoo, B. S., Kokka, R. P., and Gupta, P., 1995, Quantitation of HIV-1 RNA in plasma predicts outcome after seroconversion, Ann. Intern. Med. 122:573–579.PubMedCrossRefGoogle Scholar
  39. Miller, C. J., Alexander, N. J., Sutjipto, S., Lackner, A. A., Gettie, A., Hendrickx, A. G., Lowenstine, L. J., Jennings, M., and Marx, P. A., 1989, Genital mucosal transmission of simian immunodeficiency virus, J. Virol. 63:4277–4284.PubMedGoogle Scholar
  40. Miller, C. J., Marthas, M., Torten, J., Alexander, N. J., Moore, J. P., Doncel, G., and Hendrickx, A., 1994, Intravaginal inoculation of rhesus macaques with cell free simian immunodeficiency virus results in persistent or transient viremia, J. Virol. 68:6391–6400.PubMedGoogle Scholar
  41. Montefiori, D. C., Graham, B. S., Zhou, J. Y., Zhou, J. T., and Ahearn, J. M., 1994, Binding of human immunodeficiency virus type 1 to the C3b/C4b receptor, CRI (CD35), and red blood cells in the presence of envelope-specific antibodies and complement, J. Infect. Dis. 170:429–432.PubMedCrossRefGoogle Scholar
  42. Mosier, D. E., Culizia, R. J., Macisaac, P. D., Corey, L., and Greenberg, P. D., 1993, Resistance to human immunodeficiency virus I infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160, Proc. Natl. Acad. Sci. USA 90:2443–2447.PubMedCrossRefGoogle Scholar
  43. Mossman, S. P., Bex, E., Berglund, P., Arthos, J., O’Neil, S. P., Riley, D., Maul, D. H., Bruck, C., Momin, P., Burny, A., Fultz, P. N., Mullins, J. L., Liljestrom, P., and Hoover, E. A., 1996, Protection against lethal SIVsmmPBj14 disease by recombinant Semliki Forest virus gp160 vaccine and by a gp120 subunit vaccine, J. Virol. 70:1953–1960.PubMedGoogle Scholar
  44. Muster, T., Guinea, R., Trkola, A., Purtscher, M., Steindl, E., Palese, P., and Katinger, H., 1994, Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS, J. Virol. 68:4031–4034.PubMedGoogle Scholar
  45. Pantaleo, G., Graziosi, C., and Fauci, A. S., 1993a, Mechanisms of disease: The immunopathogenesis of human immunodeficiency virus infection, N. Engl. J. Med. 328:324–335.Google Scholar
  46. Pantaleo, G., Graziosi, C., Demarest, J. E., Butini, L., Montroni, M., Fox, C. H., Orenstein, J. M., Kotler, D. P., Fauci, A. S., 1993b, HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease, Nature 362:355–358.PubMedCrossRefGoogle Scholar
  47. Pantaleo, G., Graziosi, C., Demarest, J. E., Butini, L., Montroni, M., Fox, C. H., Orenstein, J. M., Kotler, D. P., and Fauci, A. S., 1993c, HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease, Nature 362:355–358.PubMedCrossRefGoogle Scholar
  48. Rimsky-Clarke, L., Weinhold, K. J., Arthur, L. O., Hassler, L. E., Kosloff, B., Wakefield, D., Bolognesi, D. P., and Matthews, T. J., 1996, HIV-1 evasion from immune response: Dynamic evolution in a chimpanzee of both virus and anti-HIV-1 humoral immune response, J. Virol. (submitted for publication).Google Scholar
  49. Rowland-Jones, S. L., Nixon, D. E., Aldhous, M. C., Gotch, E., Ariyoshi, K., Hallam, N., Kroll, J. S., Froebel, K., and McMichael, A. J., 1993, HIV-specific CTL activity in an HIV-exposed but uninfected infant, Lancet 341:860–861.PubMedCrossRefGoogle Scholar
  50. Rowland-Jones, S. L., Sutton, J., Ariyoshi, K., Dong, T., Gotch, E., McAdam, S., Whitby, D., Sabally S., Gallimore, A., Corrah, T., Takiguchi, M., Schultz, T., McMichael, A. J., and Whittle, H., 1995, HIV-specific cytotoxic T cells in HIV-exposed but uninfected Gambian women, Nature Med. 1:59–64.PubMedCrossRefGoogle Scholar
  51. Sattentau, Q. J., and Moore, J. P., 1995, HIV-1 neutralization is determined by epitope exposure on the gp120 oligomer, J. Exp. Med. 182:185–196.PubMedCrossRefGoogle Scholar
  52. Shibata, R., Kawamura, M., Sakai, H., Hayami, M., Ishimoto, A., and Adachi, A., 1991, Generation of a chimeric human and simian immunodeficiency virus infectious to monkey peripheral blood mononuclear cells, J. Virol. 65:3514–3520.PubMedGoogle Scholar
  53. Spira, A. I., Marx, P. A., Patterson, B. K., Mahoney, J., Koup, R. A., Wolinsky, S. M., and Ho, D. D., 1995, Cellular targets of infection and route of viral dissemination following an intravaginal inoculation of SIV into rhesus macaques, J. Exp. Med. 183:215–225.CrossRefGoogle Scholar
  54. Tindall, B., and Cooper, D. A., 1991, Primary HIV infection: Host responses and intervention strategies, AIDS 5:1–14.PubMedCrossRefGoogle Scholar
  55. Walker, B. D., and Plata, E., 1991, Cytotoxic T lymphocytes against HIV, AIDS 4:177–184.CrossRefGoogle Scholar
  56. Walker, C. M., Moody, D. J., Stites, D. P., and Levy, J. A., 1986, CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication, Science 234:1563–1566.PubMedCrossRefGoogle Scholar
  57. Walker, M. C., and Fast, P. E., 1994, Clinical trials of candidate AIDS vaccines, AIDS 8(Suppl. 1):213–236.Google Scholar
  58. Zolla-Pazner, S., and Sharpe, S., 1995, A resting cell assay for improved detection of antibody-mediated neutralization, AIDS Res. Hum. Retrovir. 11:1449–1458.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Dani P. Bolognesi
    • 1
  1. 1.Center for AIDS ResearchDuke University Medical CenterDurhamUSA

Personalised recommendations