Effect of immunization with a vaccinia-HIV env recombinant on HIV infection of chimpanzees

Abstract

Acquired immunodeficiency syndrome (AIDS) is caused by human immunodeficiency virus (HIV) and is now recognized as a worldwide epidemic for which there is no cure or vaccine. Chimpanzees are the only other animals that can be infected by HIV, and therefore the chimpanzee-HIV model system is useful for testing potential HIV vaccines. However, with one exception, there have been no reports of clinical manifestations of AIDS in chimpanzees. We report here results of an HIV vaccine trial in which nine chimpanzees were first immunized with either a recombinant vaccinia virus expressing the envelope glycoproteins of HIV strain LAV-1 (v-env5) or a control recombinant vaccinia virus and were then challenged with a high or low dose of LAV-1. Although HIV-specific antibody and T-cell responses were elicited by immunization, virus was isolated from lymphocytes of all challenged chimpanzees, indicating that immunization did not prevent infection by HIV. Among the animals that received a higher dose of LAV-1, one of two control chimpanzees, but none of the four v-env5-immunized chimpanzees developed substantial and persistent lymphadenopathy.

Recombinant Modified Vaccinia Virus Ankara Expressing the Surface gp120 of Simian Immunodeficiency Virus (SIV) Primes for a Rapid Neutralizing Antibody Response to SIV Infection in Macaques

“…These results suggest that recombinant poxviruses might prime for a similar secondary (anamnestic) neutralizing antibody response following virus infection. Hu et al showed that a recombinant vaccinia virus vector containing HIV-1 gp160 (strain LAV) primed for anamnestic neutralizing antibody production in chimpanzees following challenge with homologous virus (22). Although it is currently unknown whether an accelerated neutralizing antibody response would provide a clinical benefit in HIV-1-infected individuals, the fact that many months are needed for neutralizing antibodies to rise to detectable levels following initial infection (24,34,40,42) leaves open the possibility that it will.…”

Monoclonal Idiotypic and Anti-idiotypic Antibodies to Human Immunodeficiency Virus Type 1 Envelope Glycoprotein

“…Much of the effort to develop a vaccine for HIV infection has focused on the envelope glycoproteins. However, attempts to vaccinate chimpanzees with the entire molecule of gp 120 or with vaccinia virus recombinants bearing the HIV env protein did not elicit protection against subsequent virus challenge (Arthur et al, 1987 ;Hu et al, 1987;Berman et al, 1988). Furthermore, envelope proteins of HIV-1 were reported to have potential immunopathogenic features (Chanh et al, 1988;Chir-0000-9727 © 1991SGM mule et al, 1988Diamond et al, 1988;Weinhold et al, 1989); 'molecular mimicry' between segments of envelope proteins and domains of host proteins were also reported as a possible cause of autoimmune disorders in vivo (Weigent et al, 1986;Beretta et al, 1987;Golding et al, 1989): Therefore fragments of the virus that define critical epitopes for protective immunity, or structures that will mimic such epitopes, could be useful alternatives to existing systems as primer or stimulating immunogens.…”

New FDA drug approval policies and HIV vaccine development.

“…Another may be the somewhat discouraging results from studies of vaccine preparations . [4][5][6][7][8][9] But the years of vaccine research may pay off after all. Reports in the summer of 1989 indicate that monkeys may be protected against simian immunodeficiency virus (SIV) by a whole killed preparation of the virus.…”