AUTOLOGOUS AND HETEROLOGOUS NEUTRALIZING ANTIBODY-RESPONSES FOLLOWINGINITIAL SEROCONVERSION IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED INDIVIDUALS

In the course of human immunodeficiency virus type 1 (HIV-1) infection , patients develop a strong and persistent immune response characteriz ed by the production of HIV-specific antibodies, The aim of our study was to analyze the appearance of autologous and heterologous neutraliz ing antibodies in the sera of HIV-infected individuals, For this purpo se, primary strains have been isolated from 18 HIV-l-infected subjects prior to seroconversion (in one case) or within 1 to 8 months after s eroconversion, Sera, collected at the same time as the virus was isola ted and at various times after isolation, have been analyzed for their ability to neutralize the autologous primary strains isolated early a fter infection, heterologous primary isolates, and cell-line adapted s trains, Our neutralization assay, which combines serial dilutions of v irus and serial dilutions of sera, is based on the determination of th e serum dilution at which a fixed reduction in virus titer (90%) occur s, We have shown that (i) we could not detect autologous neutralizing antibodies in sera collected at the same time as we isolated viruses; (ii) we detected neutralizing antibodies against the autologous strain s about 1 year after seroconversion, occasionally after 8 months, but sera were not always available to exclude the presence of neutralizing antibodies at earlier times; (iii) after 1 year, the neutralization r esponse was highly specific to virus present during the early phase of HN infection; and (iv) heterologous neutralization of primary isolate s was detected later (after about 2 years), These results reveal the e normous diversity of neutralization determinants on primary isolates a s well as a temporal evolution of the humoral response generating cros s-reactive neutralizing antibodies.