Induction of humoral and cell-mediated anti-human immunodeficiency virus (HIV) responses in HIV sero-negative volunteers by immunization with recombinant gp160.

Abstract

Development of an effective vaccine for prevention of infection with HIV would provide an important mechanism for controlling the AIDS epidemic. In the current study, the first clinical trial of a candidate HIV-1 vaccine initiated in the United States, the safety and immunogenicity of escalating doses (10-1,280 Aig) of recombinant gp160 (rgpl6O), were evaluated in 138 HIV-negative volunteers. Maximal antibody responses, as evaluated by ELISA, were seen after immunization with three doses of 1,280 ;&g rgpl6O. Responses to some specific epitopes of HIV gp160, including the second conserved domain and the CD4 binding site, were seen more frequently than after natural infection. Neutralizing antibodies to the homologous HIV strain, but not heterologous strains, were induced by this regimen. Blastogenic responses to rgpl60 were seen in most volunteers receiving at least two doses of 2 20 Mg. These envelopespecific T cell responses were also seen against heterologous strains of HIV. No major adverse reactions were seen after immunization. Thus, rgpl60 is a safe and immunogenic candidate HIV vaccine; further studies are needed to determine if it will provide any clinical benefit in preventing HIV infection. (J. Clin. Invest. 1993. 92:919-928.)

Repeated Immunization with Recombinant gp160 Human Immunodeficiency Virus (HIV) Envelope Protein in Early HIV‐1 Infection: Evaluation of the T Cell Proliferative Response

“…Other studies of rgp160 have collected similar data in both HIV-1-infected and uninfected persons [11,[14][15][16][17], confirming the immunogenicity of this recombinant gp160 vaccine. The responses to rgp160 were maintained throughout the study, with some diminution in year 4 and 5, showing the ability of the immune system in HIV-1-infected persons to sustain a proliferative response.…”

“…After a series of vaccinations with a recombinant HIV-1 envelope protein (rgp160) or a whole inactivated HIV-1 preparation, HIV-1-infected persons were able to mount new proliferative responses to envelope proteins and/or new delayed-type hypersensitivity responses, as well as novel epitope-specific antibody responses, compared with natural history cohorts [10]. The same recombinant protein was also tested in HIV-1-seronegative persons in phase I trials and was shown to be safe and immunogenic [14][15][16][17].…”

HIV-specific lymphoproliferative responses in asymptomatic HIV-infected individuals

“…The question now arises of whether this defective lymphocyte response is the result of a limited immunogenicity of the virus or of a loss of the specific response during the course of disease. Much evidence allows one to rule out the first hypothesis: (i) HIV-specific T lymphocytes are present in the repertoire of healthy HIV" individuals, and can be readily activated in vitro hy repeated stimulations with antigen-pulsed APC[I8];(ii) proliferative response to gpI60 is easily detected in healthy volunteers immunized with gpI60 itself [19,20]; (iii) HIVspecific T heiper responses, detected both as IL-2-specific release and proliferation, have been reported in HIV individuals exposed to H1V and possibly protected from full infection by the development of such a response [21][22][23][24]; (iv) in vitro proliferative responses to HIV peptides can be restored by IL-12 [25]. Taken together, these findings suggest that HIV-specific T helper ceils undergo early inactivation (functional anergy rather than depletion), possibly through a preferential exposure to virus contained In specific APC.…”

Safety and Immunogenicity of Recombinant Human Immunodeficiency Virus-Like Particles in Rodents and Rhesus Macaques

“…HIV infection of chimpanzees and simian immunodeficiency virus (SIV) infection of rhesus macaques are widely used as models for HIV vac cine research. From a scries of successful active and pas sive immunisation experiments, protection in chimpan zees from HIV infection seems to be associated with an antibody response to the viral envelope glycoprotein [1][2][3][4][5], Detailed analysis of the chimpanzees' antibody re sponse revealed that a considerable portion of neutralis ing antibodies is directed to conformational and highly conserved epitopes of the gpl20 external glycoprotein in addition to the isolate-specific V3 domain [6], However, the chimpanzee model should not be overstressed as the capability of HIV to replicate in chimpanzees is limited and therefore a cryptic type of immune response might be sufficient to confer a sterilising immunity. In addition, as chimpanzees neither develop a substantial HIV-specific cytotoxic T lymphocyte (CTL) response nor AIDS-like symptoms following infection with HIV, the use of this animal model in clarifying the type of immune response, which mediates protections, is limited.…”