Abstract
Transmission studies have suggested that an optimal human immunodeficiency virus type 1 (HIV-1) vaccine should induce both neutralizing antibodies and cytolytic T cells to eliminate free virus and infected cells. A phase I trial in healthy HIV-1-seronegative persons was conducted with a combination HIV-1 vaccine regimen (strain IIIB) consisting of priming with a recombinant vaccinia (vac/env) virus expressing HIV-1 envelope and boosting with a gp160 glycoprotein derived from a recombinant baculovirus (rgp160). T-cell and antibody responses detected after immunization with either vac/env alone or rgp160 alone were generally of low magnitude and transient, and no subject developed neutralizing antibodies. In contrast, recipients of the combination regimen demonstrated in vitro T-cell proliferative responses to homologous HIV-1 antigens that were 3- to 10-fold higher than responses with either vaccine alone, and these responses were sustained for > 18 months in 75% of recipients. Moreover, both CD8+ and CD4+ cytolytic T cells were detected. Antibody responses (titer, 1:800 to 1:102,400) to homologous HIV envelope developed in all recipients of the combination regimen, and neutralizing antibodies were detected in 7 of 13. Thus, immunization with a live virus vaccine followed by boosting with a soluble protein offers promise for inducing the broad immunity needed in an HIV vaccine.
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- Aldovini A., Young R. A. Humoral and cell-mediated immune responses to live recombinant BCG-HIV vaccines. Nature. 1991 Jun 6;351(6326):479–482. doi: 10.1038/351479a0. [DOI] [PubMed] [Google Scholar]
- Bennink J. R., Yewdell J. W., Smith G. L., Moller C., Moss B. Recombinant vaccinia virus primes and stimulates influenza haemagglutinin-specific cytotoxic T cells. Nature. 1984 Oct 11;311(5986):578–579. doi: 10.1038/311578a0. [DOI] [PubMed] [Google Scholar]
- Berman P. W., Riddle L., Nakamura G., Haffar O. K., Nunes W. M., Skehel P., Byrn R., Groopman J., Matthews T., Gregory T. Expression and immunogenicity of the extracellular domain of the human immunodeficiency virus type 1 envelope glycoprotein, gp160. J Virol. 1989 Aug;63(8):3489–3498. doi: 10.1128/jvi.63.8.3489-3498.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chakrabarti S., Robert-Guroff M., Wong-Staal F., Gallo R. C., Moss B. Expression of the HTLV-III envelope gene by a recombinant vaccinia virus. Nature. 1986 Apr 10;320(6062):535–537. doi: 10.1038/320535a0. [DOI] [PubMed] [Google Scholar]
- Chesebro B., Wehrly K. Development of a sensitive quantitative focal assay for human immunodeficiency virus infectivity. J Virol. 1988 Oct;62(10):3779–3788. doi: 10.1128/jvi.62.10.3779-3788.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Coombs R. W., Collier A. C., Allain J. P., Nikora B., Leuther M., Gjerset G. F., Corey L. Plasma viremia in human immunodeficiency virus infection. N Engl J Med. 1989 Dec 14;321(24):1626–1631. doi: 10.1056/NEJM198912143212402. [DOI] [PubMed] [Google Scholar]
- Cooney E. L., Collier A. C., Greenberg P. D., Coombs R. W., Zarling J., Arditti D. E., Hoffman M. C., Hu S. L., Corey L. Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. Lancet. 1991 Mar 9;337(8741):567–572. doi: 10.1016/0140-6736(91)91636-9. [DOI] [PubMed] [Google Scholar]
- Dolin R., Graham B. S., Greenberg S. B., Tacket C. O., Belshe R. B., Midthun K., Clements M. L., Gorse G. J., Horgan B. W., Atmar R. L. The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network. Ann Intern Med. 1991 Jan 15;114(2):119–127. doi: 10.7326/0003-4819-114-2-119. [DOI] [PubMed] [Google Scholar]
- Gardner M. B. Vaccination against SIV infection and disease. AIDS Res Hum Retroviruses. 1990 Jul;6(7):835–846. doi: 10.1089/aid.1990.6.835. [DOI] [PubMed] [Google Scholar]
- Graham B. S., Belshe R. B., Clements M. L., Dolin R., Corey L., Wright P. F., Gorse G. J., Midthun K., Keefer M. C., Roberts N. J., Jr Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. The AIDS Vaccine Clinical Trials Network. J Infect Dis. 1992 Aug;166(2):244–252. doi: 10.1093/infdis/166.2.244. [DOI] [PubMed] [Google Scholar]
- Hu S. L., Abrams K., Barber G. N., Moran P., Zarling J. M., Langlois A. J., Kuller L., Morton W. R., Benveniste R. E. Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160. Science. 1992 Jan 24;255(5043):456–459. doi: 10.1126/science.1531159. [DOI] [PubMed] [Google Scholar]
- Jaraquemada D., Marti M., Long E. O. An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells. J Exp Med. 1990 Sep 1;172(3):947–954. doi: 10.1084/jem.172.3.947. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keefer M. C., Bonnez W., Roberts N. J., Jr, Dolin R., Reichman R. C. Human immunodeficiency virus (HIV-1) gp160-specific lymphocyte proliferative responses of mononuclear leukocytes from HIV-1 recombinant gp160 vaccine recipients. J Infect Dis. 1991 Mar;163(3):448–453. doi: 10.1093/infdis/163.3.448. [DOI] [PubMed] [Google Scholar]
- Krieger J. N., Coombs R. W., Collier A. C., Ross S. O., Chaloupka K., Cummings D. K., Murphy V. L., Corey L. Recovery of human immunodeficiency virus type 1 from semen: minimal impact of stage of infection and current antiviral chemotherapy. J Infect Dis. 1991 Feb;163(2):386–388. doi: 10.1093/infdis/163.2.386. [DOI] [PubMed] [Google Scholar]
- Morrison L. A., Braciale V. L., Braciale T. J. Antigen form influences induction and frequency of influenza-specific class I and class II MHC-restricted cytolytic T lymphocytes. J Immunol. 1988 Jul 15;141(2):363–368. [PubMed] [Google Scholar]
- Moss B., Flexner C. Vaccinia virus expression vectors. Annu Rev Immunol. 1987;5:305–324. doi: 10.1146/annurev.iy.05.040187.001513. [DOI] [PubMed] [Google Scholar]
- Orentas R. J., Hildreth J. E., Obah E., Polydefkis M., Smith G. E., Clements M. L., Siliciano R. F. Induction of CD4+ human cytolytic T cells specific for HIV-infected cells by a gp160 subunit vaccine. Science. 1990 Jun 8;248(4960):1234–1237. doi: 10.1126/science.2190315. [DOI] [PubMed] [Google Scholar]
- Riddell S. R., Rabin M., Geballe A. P., Britt W. J., Greenberg P. D. Class I MHC-restricted cytotoxic T lymphocyte recognition of cells infected with human cytomegalovirus does not require endogenous viral gene expression. J Immunol. 1991 Apr 15;146(8):2795–2804. [PubMed] [Google Scholar]
- Rooney J. F., Wohlenberg C., Cremer K. J., Moss B., Notkins A. L. Immunization with a vaccinia virus recombinant expressing herpes simplex virus type 1 glycoprotein D: long-term protection and effect of revaccination. J Virol. 1988 May;62(5):1530–1534. doi: 10.1128/jvi.62.5.1530-1534.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shen L., Chen Z. W., Miller M. D., Stallard V., Mazzara G. P., Panicali D. L., Letvin N. L. Recombinant virus vaccine-induced SIV-specific CD8+ cytotoxic T lymphocytes. Science. 1991 Apr 19;252(5004):440–443. doi: 10.1126/science.1708168. [DOI] [PubMed] [Google Scholar]
- Tacket C. O., Baqar S., Munoz C., Murphy J. R. Lymphoproliferative responses to mitogens and HIV-1 envelope glycoprotein among volunteers vaccinated with recombinant gp160. AIDS Res Hum Retroviruses. 1990 Apr;6(4):535–542. doi: 10.1089/aid.1990.6.535. [DOI] [PubMed] [Google Scholar]
- Tartaglia J., Pincus S., Paoletti E. Poxvirus-based vectors as vaccine candidates. Crit Rev Immunol. 1990;10(1):13–30. [PubMed] [Google Scholar]
- Zagury D., Bernard J., Cheynier R., Desportes I., Leonard R., Fouchard M., Reveil B., Ittele D., Lurhuma Z., Mbayo K. A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS. Nature. 1988 Apr 21;332(6166):728–731. doi: 10.1038/332728a0. [DOI] [PubMed] [Google Scholar]
- Zarling J. M., Eichberg J. W., Moran P. A., McClure J., Sridhar P., Hu S. L. Proliferative and cytotoxic T cells to AIDS virus glycoproteins in chimpanzees immunized with a recombinant vaccinia virus expressing AIDS virus envelope glycoproteins. J Immunol. 1987 Aug 15;139(4):988–990. [PubMed] [Google Scholar]
- el-Ad B., Roth Y., Winder A., Tochner Z., Lublin-Tennenbaum T., Katz E., Schwartz T. The persistence of neutralizing antibodies after revaccination against smallpox. J Infect Dis. 1990 Mar;161(3):446–448. doi: 10.1093/infdis/161.3.446. [DOI] [PubMed] [Google Scholar]