Plaque Transfer Assay for Detecting Neutralizing Antibodies to HTLV-III (AIDS). HIV-1 Inactivation by Antibodies: Predominance of a Group-Specific Epitope that Persists Despite Genetic Variation

摘要

We have analyzed the antibody sensitivity of three divergent isolates of HIV-1 in a new plaquing assay that detects human retroviruses as discrete, macroscopic plaques. Because each plaque derives from a single viral infection event, the plaques are highly sensitive to inactivation by neutralizing antibodies. Sera of infected asymptomatic patients were tested for neutralizing activity against one, two or all three viral isolates, to determine neutralizing titer and specificity. All infected patients made neutralizing antibodies, and the predominant antibodies were group-specific, as defined by the ability to neutralize divergent strains of HIV-1 equally. All 3 viruses shared one or more group-specific neutralizing epitopes, in spite of the high degree of genetic diversity and distant geographic origins among them. None of the three isolates showed significant antigenic drift or even a modes frequency of antibody resistant variants. The apparent lack of antibody resistance among otherwise viruses suggests that HIV-1, by evading neutralizing antibodies during most of its life cycle, may have lost an important mechanism for selecting antibody resistant variants from a large pool of random mutants. These findings may be relevant to vaccine design, if it becomes possible for vaccine antigens to elicit similar group-specific neutralizing antibodies prior to infection. (AW)