Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals

Abstract

In the course of human immunodeficiency virus type 1 (HIV-1) infection, patients develop a strong and persistent immune response characterized by the production of HIV-specific antibodies. The aim of our study was to analyze the appearance of autologous and heterologous neutralizing antibodies in the sera of HIVinfected individuals. For this purpose, primary strains have been isolated from 18 HIV-1-infected subjects prior to seroconversion (in one case) or within 1 to 8 months after seroconversion. Sera, collected at the same time as the virus was isolated and at various times after isolation, have been analyzed for their ability to neutralize the autologous primary strains isolated early after infection, heterologous primary isolates, and cell-line adapted strains. Our neutralization assay, which combines serial dilutions of virus and serial dilutions of sera, is based on the determination of the serum dilution at which a fixed reduction in virus titer (90%) occurs. 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 strains 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 response was highly specific to virus present during the early phase of HIV infection; and (iv) heterologous neutralization of primary isolates was detected later (after about 2 years). These results reveal the enormous diversity of neutralization determinants on primary isolates as well as a temporal evolution of the humoral response generating cross-reactive neutralizing antibodies.

Mother to child transmission of HIV‐1 in a Thai population: Role of virus characteristics and maternal humoral immune response

“…The data presented above on heterologous neutralizing antibodies against primary HIV-1 isolates were consistent with those of others, showing that heterologous antibodies were detected at low frequency and titer [Moog et al, 1997;Pilgrim et al, 1997;Bongertz et al, 2001;Guevara et al, 2002]. However, a recent study of Thai samples found that the higher the titer of neutralizing antibodies, the lower the rate of mother to child transmission of HIV-1 [Barin et al, 2006].…”

“…Although it is now generally regarded that T-cell adapted stains may not be relevant as a measure for in vivo neutralizing responses [Zolla-Pazner, 1996], most previous studies on heterologous neutralizing antibodies used laboratory-adapted HIV-1 strains, which have more accessible neutralization epitopes [Beddows et al, 1998], thus providing neutralization titers across a wide range. In contrast, heterologous or autologous neutralizing antibodies against primary HIV-1 isolates are always detected at a low frequency and level, leaving only a narrow range of titers for comparison [Moog et al, 1997;Pilgrim et al, 1997;Bongertz et al, 2001;Guevara et al, 2002]. For the sake of completeness, this study utilized both a laboratory-adapted strain, HIV-1 MN, and primary isolates.…”

Identification and characterization of sera from HIV-infected individuals with broad cross-neutralizing activity against group M (env clade A-H) and group O primary HIV-1 isolates

“…Although the production of antibodies is efficient and used as a marker for serological diagnosis of infection, most antibodies do not exert neutralizing activity against primary virus isolates. Antibodies with neutralizing capacity against primary isolates emerge relatively late after seroconversion (>1 year post-infection) when the neutralizing activity is monitored on primary lymphocytes, and their neutralization spectrum broadens in time, revealing a temporal evolution of the humoral immune response generating cross-reactive neutralizing antibodies [Moog et al, 1997;Nyambi et al, 1997]. A correlation between the appearance of neutralizing antibodies and a decrease in viral load has been observed [Lathey et al, 1997].…”

Neutralization of HIV‐1 subtypes: Implications for vaccine formulations

“…A number of groups have observed a discrepancy between the neutralization of primary isolates and cell line-adapted strains [Wrin et al, 1995;Mascola et al, 1996;Moore et al, 1996;Moog et al, 1997], namely, the primary isolates are more resistant to neutralization than their laboratory-adapted strains.…”