A vaccine of conserved SIV envelope peptides protects macaques against SIV challenge.

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

A vaccine of conserved SIV envelope peptides protects macaques against SIV challenge.

Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:53 (abstract no. 37). Unique Identifier : AIDSLINE PRIM8/900037
Eddy GA; Shafferman A; Jahrling PB; Benveniste RE; Lewis MG; Phipps TJ; Eden-McCutchan F; Sadoff J; Burke DS; Jackson Foundation Research Lab, Rockville, MD

Abstract: Rhesus monkeys were immunized with a cocktail of four recombinant-origin fusion proteins of beta-galactosidase (beta-gal) and simian immunodeficiency virus (SIV) envelope peptides, SIV-88, SIV-500, SIV-582 and SIV-647. The peptides are 10 to 21 residue segments of conserved, hydrophilic regions of SIV gp120 and transmembrane proteins. They are based on analogous peptides from similarly selected regions of the human immunodeficiency virus (HIV) envelope previously found to be immunoreactive with HIV-infected patient sera. Controls were immunized with beta-gal only. During the year of immunization, the vaccinated macaques exhibited antibodies by ELISA to all of the individual peptides, and they eventually developed virus neutralizing antibodies as measured by syncitia-inhibition assay. Three weeks after the fourth inoculation of vaccine, the immunized and control monkeys were challenged with about 100 cell culture infectious doses of a biological clone of SIV/Mne (E11S). Following challenge, the control monkeys developed gradually increasing, and eventually high titer, ELISA antibodies and extensive immunoblot responses to all major viral proteins, but the immunized monkeys developed a more brisk anamnestic response, primarily to the SIV envelope polypeptides, within 3 to 6 weeks after challenge. The immunized monkeys then exhibited a gradual, fluctuating decline in SIV antibody titers. All immunized and control monkeys became infected following virus challenge as determined by virus isolation or by polymerase chain reaction detection of viral genomic elements in circulating cells during the initial weeks after infection. However, the interval of virus positivity in the immunized monkeys was relatively brief, and one of the immunized monkeys (3X7) was never virus positive. Monkey 3X7 also had the highest prechallenge virus neutralizing antibody titer and the lowest postchallenge antibody response. Moreover, the degree of suppression of SIV proliferation by immunized monkeys correlated with neutralizing antibody titers on the day of challenge and ELISA titers to the transmembrane peptide, SIV-647. At 60 weeks after infection, all immunized monkeys were healthy and have remained virus negative by coculture, whereas all controls were virus positive, and two appeared to have declining CD4+ T cells. The immunologic and structural parallelism between the selected SIV peptides and the corresponding, equally conserved, HIV envelope peptides suggests that a preexposure immunization strategy in humans incorporating an analogous, synthetic HIV peptide vaccine may broadly protect against disease by HIV.

Keywords: Animal Antibodies, Viral/*BIOSYNTHESIS Cells, Cultured Cytopathogenic Effect, Viral CD4-Positive T-Lymphocytes/MICROBIOLOGY Enzyme-Linked Immunosorbent Assay HIV/IMMUNOLOGY HIV Infections/*PREVENTION & CONTROL Macaca mulatta Neutralization Tests Polymerase Chain Reaction Solubility SIV/GROWTH & DEVELOPMENT/*IMMUNOLOGY Vaccines, Synthetic Viral Envelope Proteins/*IMMUNOLOGY *Viral Vaccines Virus Cultivation Virus Replication ABSTRACT
910730
M9170957

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