EVOLUTION OF NEUTRALIZING ANTIBODY-RESPONSE AGAINST HIV TYPE-1 VIRIONS AND PSEUDOVIRIONS IN MULTICENTER AIDS COHORT STUDY PARTICIPANTS

Changes in neutralizing antibody (NA) titers in stored sera collected over 5 years from 10 participants in the Multicenter AIDS Cohort Study (MACS) were evaluated, The participants were HIV-1 infected on enroll ment in the MACS, and remained AIDS free during the 5-year study inter val. Seven viruses derived from molecular clones were used in NA assay s; five of the viruses were T tropic (NL4-3, ALA1, NY5, SF2, and Z2Z6) and two were M tropic [AD8 and NL(SF162)]. In addition, pseudoviruses (PVs) were constructed that expressed envelope genes from NL4-3, ALA1 , AD8, and SF162 and from primary viruses from two MACS participants ( PV-9 and PV-10). There was significant correlation between NA titers o btained in four of five virus/PV comparisons, while the SF162 PV was m ore sensitive to NA than the corresponding virus. Comparable changes i n NA titers were detected using viruses and PVs. Fourfold or greater i ncreases in NA titers were noted in each of the participants, involvin g recognition of one to five of the nine strains tested. In some patie nts these NA titer changes appeared as discrete episodes of immune res ponses, while in others there may have been either multiple episodes o r continuous evolution of the NA responses. The data indicate that cha nges in NA specificity occur during HIV-1 infection, which may result from the occurrence of neutralization escape mutation. The use of PVs for the study of phenotypic characteristics of envelope glycoproteins should facilitate the study of neutralization escape mutation in HIV-1 infection.