Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
VARIATION IN SUSCEPTIBILITY OF HUMAN IMMUNODEFICIENCY VIRUSES TO NEUTRALIZING ANTIBODIES
Vaccines 87. Modern Approaches to New Vaccines: Prevention of AIDS and Other Viral, Bacterial, and Parasitic Diseases. Chanock RM et al, eds. New York, Cold Spring Harbor Laboratory, p. 194-8, 1987.. Unique Identifier : AIDSLINE ICDB/88647978 Prince AM; Pascual D; Kurokawa D; Baker L; Lab. of Virology, Lindsley F. Kimball Res. Inst. of the New York; Blood Center, New York, NY 10021
Abstract:
The extraordinary variability in the sequence of envelope genes of human immunodeficiency virus strains has raised concern that concomitant antigenic variation might prevent potential vaccines from achieving broad protective efficacy. To address this question, quantitative neutralization assays were carried out using an automated microtiter test. This assay uses 100 TCID50 of test viruses incubated with serial dilutions of heat-inactivated sera and then cultivated with H-9 cells for 14 days prior to determination of viral replication by reverse transcriptase assay. To determine specificity, 222 sera from male homosexuals under code were tested. When the code was broken, 44 sera were found to be negative for anti-HTLV-III by direct ELISA. Of these sera, 42 were negative for neutralizing antibody, and 2 had borderline titers. The test is thus highly specific. Titration of neutralizing antibody titers in sera from 178 male homosexuals with anti-HTLV-III revealed that 92.7% had demonstrable neutralizing antibodies; 12.5% had titers above 1:128. In a preliminary attempt to evaluate virus strain variation in epitopes that combine with neutralizing antibodies, neutralizing antibody titers of seven sera were tested against five different strains of acquired immune deficiency virus. All virus stocks were grown and titrated in H-9 cells. Two virus strains (ARV-4 and NYBC-014) showed identical patterns of response and were highly sensitive to neutralization by all of the antisera tested. The prototype HTLV-IIIB strain was slightly less sensitive to neutralization by three of the sera tested. Two virus strains (NYBC-017 and NYBC-023) were less sensitive to neutralization by some, but not all, of the sera tested. Virus could be isolated from blood containing high titers of neutralizing antibody against the homologous isolate (eg, NYBC-014). The data suggest variability in susceptibility to neutralization between strains; however, the variation appears to be quantitative and not absolute. The prospect for achieving broad protective efficacy with recombinant DNA-derived vaccines derived from a single viral genome thus appears promising. (6 Refs)
Keywords: Antibodies, Viral/*ANALYSIS *Antigenic Variation Antigens, Viral/IMMUNOLOGY Cell Line Human HIV/*IMMUNOLOGY/PHYSIOLOGY *Neutralization Tests Virus Replication MEETING PAPER
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Important note: Information in this article was accurate in 1988. The state of the art may have changed since the publication date.
