A perspective on AIDS vaccines

Science

Volumn 272, Issue 5270, 1996, Pages 1888-1890

  Bloom, Barry R ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; RNA DIRECTED DNA POLYMERASE INHIBITOR;

DRUG DESIGN; DRUG EFFICACY; DRUG MANUFACTURE; DRUG RESEARCH; DRUG SAFETY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MACACA; NONHUMAN; NOTE; PRIORITY JOURNAL; T LYMPHOCYTE; VACCINE PRODUCTION;

ACQUIRED IMMUNODEFICIENCY SYNDROME; AIDS VACCINES; CLINICAL TRIALS; HUMANS;

HUMAN IMMUNODEFICIENCY VIRUS; MACACA;

EID: 0030017740     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.272.5270.1888     Document Type: Note

References (42)

1. Some excellent recent reviews of AIDS vaccines and issues include M. C. Walker and P. E. Fast, AIDS B (suppl. 1), S213 (1994); M. L. Clements, in New Generation Vaccines, M. M. Levine, Ed. (Dekker, New York, ed. 2, in press).
2. Some excellent recent reviews of AIDS vaccines and issues include M. C. Walker and P. E. Fast, AIDS B (suppl. 1), S213 (1994); M. L. Clements, in New Generation Vaccines, M. M. Levine, Ed. (Dekker, New York, ed. 2, in press).
3. B. F. Haynes, G. Pantaleo, A. S. Fauci, Science 271, 324 (1996); W. E. Paul, Cell 82, 177 (1995); R. A. Weiss, AIDS Res. Hum. Retroviruses 12, 465 (1996).
4. B. F. Haynes, G. Pantaleo, A. S. Fauci, Science 271, 324 (1996); W. E. Paul, Cell 82, 177 (1995); R. A. Weiss, AIDS Res. Hum. Retroviruses 12, 465 (1996).
5. B. F. Haynes, G. Pantaleo, A. S. Fauci, Science 271, 324 (1996); W. E. Paul, Cell 82, 177 (1995); R. A. Weiss, AIDS Res. Hum. Retroviruses 12, 465 (1996).
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8. World Bank, Investing in Health, World Development Report 1993 (Oxford Univ Press, New York, 1993), pp. 62-63.
9. Estimates range from $12,000 to $20,000 per year per patient.
10. See reviews by L. K. Schrager et al., AIDS 8 (suppl. 1), S95 (1994); S. L. Rowland-Jones and A. McMichael, Curr. Opin. Immunol. 7, 448 (1995); A. Munoz et al., Am. J. Epidemiol. 130, 530 (1989); S. P. Buchbinder et al., AIDS 8, 1123 (1994); I. P. M. Keet et al., J. Infect. Dis. 169, 1236 (1994); Y. Cao, L. Qin, L. Zhang, J. Safrit, D. D. Ho, N. Engl. J. Med. 332, 201 (1995); G. Pantaleo et al., ibid., p. 209.
11. See reviews by L. K. Schrager et al., AIDS 8 (suppl. 1), S95 (1994); S. L. Rowland-Jones and A. McMichael, Curr. Opin. Immunol. 7, 448 (1995); A. Munoz et al., Am. J. Epidemiol. 130, 530 (1989); S. P. Buchbinder et al., AIDS 8, 1123 (1994); I. P. M. Keet et al., J. Infect. Dis. 169, 1236 (1994); Y. Cao, L. Qin, L. Zhang, J. Safrit, D. D. Ho, N. Engl. J. Med. 332, 201 (1995); G. Pantaleo et al., ibid., p. 209.
12. See reviews by L. K. Schrager et al., AIDS 8 (suppl. 1), S95 (1994); S. L. Rowland-Jones and A. McMichael, Curr. Opin. Immunol. 7, 448 (1995); A. Munoz et al., Am. J. Epidemiol. 130, 530 (1989); S. P. Buchbinder et al., AIDS 8, 1123 (1994); I. P. M. Keet et al., J. Infect. Dis. 169, 1236 (1994); Y. Cao, L. Qin, L. Zhang, J. Safrit, D. D. Ho, N. Engl. J. Med. 332, 201 (1995); G. Pantaleo et al., ibid., p. 209.
13. See reviews by L. K. Schrager et al., AIDS 8 (suppl. 1), S95 (1994); S. L. Rowland-Jones and A. McMichael, Curr. Opin. Immunol. 7, 448 (1995); A. Munoz et al., Am. J. Epidemiol. 130, 530 (1989); S. P. Buchbinder et al., AIDS 8, 1123 (1994); I. P. M. Keet et al., J. Infect. Dis. 169, 1236 (1994); Y. Cao, L. Qin, L. Zhang, J. Safrit, D. D. Ho, N. Engl. J. Med. 332, 201 (1995); G. Pantaleo et al., ibid., p. 209.
14. See reviews by L. K. Schrager et al., AIDS 8 (suppl. 1), S95 (1994); S. L. Rowland-Jones and A. McMichael, Curr. Opin. Immunol. 7, 448 (1995); A. Munoz et al., Am. J. Epidemiol. 130, 530 (1989); S. P. Buchbinder et al., AIDS 8, 1123 (1994); I. P. M. Keet et al., J. Infect. Dis. 169, 1236 (1994); Y. Cao, L. Qin, L. Zhang, J. Safrit, D. D. Ho, N. Engl. J. Med. 332, 201 (1995); G. Pantaleo et al., ibid., p. 209.
15. See reviews by L. K. Schrager et al., AIDS 8 (suppl. 1), S95 (1994); S. L. Rowland-Jones and A. McMichael, Curr. Opin. Immunol. 7, 448 (1995); A. Munoz et al., Am. J. Epidemiol. 130, 530 (1989); S. P. Buchbinder et al., AIDS 8, 1123 (1994); I. P. M. Keet et al., J. Infect. Dis. 169, 1236 (1994); Y. Cao, L. Qin, L. Zhang, J. Safrit, D. D. Ho, N. Engl. J. Med. 332, 201 (1995); G. Pantaleo et al., ibid., p. 209.
16. See reviews by L. K. Schrager et al., AIDS 8 (suppl. 1), S95 (1994); S. L. Rowland-Jones and A. McMichael, Curr. Opin. Immunol. 7, 448 (1995); A. Munoz et al., Am. J. Epidemiol. 130, 530 (1989); S. P. Buchbinder et al., AIDS 8, 1123 (1994); I. P. M. Keet et al., J. Infect. Dis. 169, 1236 (1994); Y. Cao, L. Qin, L. Zhang, J. Safrit, D. D. Ho, N. Engl. J. Med. 332, 201 (1995); G. Pantaleo et al., ibid., p. 209.
17. S. Rowland-Jones et al., Nature Med. 1, 59 (1995); F. A. Plummer et al., Ninth International Conference on AIDS-STD World Congress, Berlin, 6 to 11 June 1993, abstr. WS-807-3.
18. S. Rowland-Jones et al., Nature Med. 1, 59 (1995); F. A. Plummer et al., Ninth International Conference on AIDS-STD World Congress, Berlin, 6 to 11 June 1993, abstr. WS-807-3.
19. K. Travers et al., Science 268, 1612 (1995).
20. Y. J. Bryson et al., N. Engl. J. Med. 332, 833 (1995); S. S. Bakshi et al., Pediatr. Infect. Dis. J. 14, 658 (1995); P. A. Roques et al., AIDS 9, F19 (1995); O. P. Morris et al., J. Infect. Dis. 173, 68 (1996); M. L. Newell et al., Lancet 347, 213 (1996).
21. Y. J. Bryson et al., N. Engl. J. Med. 332, 833 (1995); S. S. Bakshi et al., Pediatr. Infect. Dis. J. 14, 658 (1995); P. A. Roques et al., AIDS 9, F19 (1995); O. P. Morris et al., J. Infect. Dis. 173, 68 (1996); M. L. Newell et al., Lancet 347, 213 (1996).
22. Y. J. Bryson et al., N. Engl. J. Med. 332, 833 (1995); S. S. Bakshi et al., Pediatr. Infect. Dis. J. 14, 658 (1995); P. A. Roques et al., AIDS 9, F19 (1995); O. P. Morris et al., J. Infect. Dis. 173, 68 (1996); M. L. Newell et al., Lancet 347, 213 (1996).
23. Y. J. Bryson et al., N. Engl. J. Med. 332, 833 (1995); S. S. Bakshi et al., Pediatr. Infect. Dis. J. 14, 658 (1995); P. A. Roques et al., AIDS 9, F19 (1995); O. P. Morris et al., J. Infect. Dis. 173, 68 (1996); M. L. Newell et al., Lancet 347, 213 (1996).
24. Y. J. Bryson et al., N. Engl. J. Med. 332, 833 (1995); S. S. Bakshi et al., Pediatr. Infect. Dis. J. 14, 658 (1995); P. A. Roques et al., AIDS 9, F19 (1995); O. P. Morris et al., J. Infect. Dis. 173, 68 (1996); M. L. Newell et al., Lancet 347, 213 (1996).
25. Colloquium on Feline Leukemia/Feline Immunodeficiency Tests and Vaccination, J. Am. Vet. Med. Assoc. 10, 1392 (1991).
26. M. D. Daniel, F, Kirchhoff, S. C. Czajak, P. K. Sehgal, R. C. Desrosiers, Science 258, 1938 (1992); B. L. Lohman et al., J. Virol. 68, 7021 (1994); N. Almond et al., Lancet 345, 1342 (1995).
27. M. D. Daniel, F, Kirchhoff, S. C. Czajak, P. K. Sehgal, R. C. Desrosiers, Science 258, 1938 (1992); B. L. Lohman et al., J. Virol. 68, 7021 (1994); N. Almond et al., Lancet 345, 1342 (1995).
28. M. D. Daniel, F, Kirchhoff, S. C. Czajak, P. K. Sehgal, R. C. Desrosiers, Science 258, 1938 (1992); B. L. Lohman et al., J. Virol. 68, 7021 (1994); N. Almond et al., Lancet 345, 1342 (1995).
29. Y. Feng, C. C. Broder, P. E. Kennedy, E. A. Berger, Science 272, 872 (1996).
30. The World Health Organization's position is that any decision to proceed with phase III trials must be made by the national government of the host country [J. Moore and R. Anderson, Nature 372, 313 (1994)]. Phase III trials of two gp120 subunit vaccine candidates are being planned for Thailand.
31. In the absence of known correlates of protection, some criteria that ought to be considered are induction of (i) antibodies that neutralize human isolates; (ii) cytotoxic T cells; (iii) mucosal immunity; (iv) immunologic memory; (v) persistence of immune responses for more than a few weeks; (vi) significant protection in a relevant primate model against challenge with homologous virus, heterologous virus, and virus-infected cells; and (vii) possible long-term adverse effects.
32. Former Senator Russell B. Long of Louisiana, engaged by MicroGeneSys, successfully lobbied Congress to provide $20 million to the Department of Defense to carry out a large-scale trial of its recombinant gp160 vaccine before demonstrating that it had any clinical benefit in a phase II therapeutic trial. It did not ("Maker of an AIDS vaccine says test found no benefit," New York Times, 19 April 1996, p. A18).
33. The current phase II trial strategies for priming T cells with a viral vector and boosting with subunit formulations to generate antibodies, combining products from different companies, represents an admirable approach to minimizing the risks of phase III "failure."
34. Incidence rates range from 6% in some cohorts to as high as 16% in the subpopulation of sex workers [H. L. Martin Jr. et al., AIDS Res. Hum. Retroviruses 10 (suppl. 2), S235 (1994)].
35. Cohort studies (HIVNET) and AIDS Vaccine Evaluation Units represent 21% of NIAID AIDS vaccine expenditures. Whether that is an appropriate proportion of vaccine research funds, and whether the number of sites is appropriate in the absence of vaccines ready for phase III trials, are questions currently under review by NIAID.
36. One of the concerns common to naked DNA and attenuated retroviral vaccines is the possibility of their random integration into tumor suppressor genes, leading to induction of tumors, for which there is precedent with HIV itself [B. Shiramizu, B. G. Herndier, M. S. McGrath, Cancer Res. 54, 2069 (1994)]. The major concern about live attenuated retroviral vaccine strains, even deletion mutants, is that they might revert to virulence upon superinfection with HIV, transplacental transfer to newborns, or transfer to immunodeficient hosts [R. M. Ruprecht et al., AIDS Res. Hum. Retroviruses 12, 459 (1996)] or by recombining with retroviral homologous sequences scattered across the human genome [see also R. C. Desrosiers, ibid. 10, 331 (1994)].
37. One of the concerns common to naked DNA and attenuated retroviral vaccines is the possibility of their random integration into tumor suppressor genes, leading to induction of tumors, for which there is precedent with HIV itself [B. Shiramizu, B. G. Herndier, M. S. McGrath, Cancer Res. 54, 2069 (1994)]. The major concern about live attenuated retroviral vaccine strains, even deletion mutants, is that they might revert to virulence upon superinfection with HIV, transplacental transfer to newborns, or transfer to immunodeficient hosts [R. M. Ruprecht et al., AIDS Res. Hum. Retroviruses 12, 459 (1996)] or by recombining with retroviral homologous sequences scattered across the human genome [see also R. C. Desrosiers, ibid. 10, 331 (1994)].
38. One of the concerns common to naked DNA and attenuated retroviral vaccines is the possibility of their random integration into tumor suppressor genes, leading to induction of tumors, for which there is precedent with HIV itself [B. Shiramizu, B. G. Herndier, M. S. McGrath, Cancer Res. 54, 2069 (1994)]. The major concern about live attenuated retroviral vaccine strains, even deletion mutants, is that they might revert to virulence upon superinfection with HIV, transplacental transfer to newborns, or transfer to immunodeficient hosts [R. M. Ruprecht et al., AIDS Res. Hum. Retroviruses 12, 459 (1996)] or by recombining with retroviral homologous sequences scattered across the human genome [see also R. C. Desrosiers, ibid. 10, 331 (1994)].
39. The OAR review recommended that an NIH Study Section on Vaccines, not limited to AIDS vaccines, be established with panels of scientists with both academic and industry experience. Much of the AIDS vaccine effort is supported by contracts that may limit flexibility and innovation. Other kinds of funding mechanisms, such as cooperative agreements and program project grants, might be considered.
40. NIH AIDS Research Program Evaluation, Summary Report, and Report on Vaccine Research and Development (Office of AIDS Research, NIH, Bethesda, MD, 1996).
41. Attributed to atomic physicist Leo Szilard.
42. I wish to thank many colleagues for generously sharing their thoughts and knowledge, including D. Bolognesi, M. L. Clements, P. Fast, S, Berkley, D. Ho, B. Mathieson, J. Moore, and W. Paul.