Search

Objectives: To determine the neutralizing antibody patterns to HIV-1ANT70 (ANT70) and HIV-1IIIB (IIIB) in human sera obtained from HIV-1-infected individuals from different African countries and Belgium. Second, to correlate the presence of neutralizing antibodies in sera and their ability to bind to synthetic peptides derived from eight different HIV-1 V3 loop sequences., Design and Methods: Forty sera from Belgium and 88 obtained from seven countries in Africa were tested for their ability to neutralize ANT70 (one of the most genetically divergent HIV-1 isolates documented), and IIIB. Sera found to cross-neutralize both viruses were further challenged with four HIV-1 field isolates. All sera were tested on a panel of V3 loop peptides obtained from different HIV-1 genotypes., Results: Four patterns of sera were identified, including 33 (26%) sera not neutralizing any of the isolates, seven (5%) sera neutralizing only ANT70, 45 (35%) sera neutralizing only IIIB, and 43 (34%) sera cross-neutralizing both isolates. Sera capable of cross-neutralizing both ANT70 and IIIB consistently neutralized other field isolates tested, with a remarkable similarity in neutralizing antibody titre. A significantly higher number of sera cross-neutralizing both ANT70 and IIIB compared with sera lacking neutralizing antibodies, reacted simultaneously in enzyme-linked immunosorbent assays (ELISA) with three or more V3 loop peptides belonging to HIV-1 strains of different genotypes. However, none of the sera cross-neutralizing ANT70 and IIIB were reactive in ELISA with the ANT70 V3 loop peptide., Conclusion: These results suggest that despite pronounced genomic variation of the HIV-1ANT70 isolate, there are strongly conserved neutralizing epitopes situated outside the V3 loop that are shared by other HIV-1 isolates. These findings suggest that genetic variation might be surmountable in the design of a polyvalent HIV vaccine, if neutralizing antibodies are found to be correlates of protection in HIV infection.

Objective: To determine the value of (combinations of) synthetic peptides representing immunodominant sites on HIV-1/HIV-2 transmembrane proteins for the detection and discrimination between HIV-1 and HIV-2 infection in various populations., Design and Methods: Two 24-mer synthetic peptides derived from immunodominant sites on the HIV-1 and HIV-2 transmembrane proteins were used separately, in combination (env 1/2), and in combination with recombinant p24 (p24/env) in enzyme-linked immunosorbent assays., Results: Positive reactions with env-1 were found in 150 out of 150 (100%) samples from Dutch AIDS patients, 60 out of 60 (100%) samples from Dutch homosexual men obtained 1 year after HIV-1-antibody seroconversion, 29 out of 30 (96.7%) samples from these men obtained at the time of HIV-1-antibody seroconversion, 40 out of 41 (97.6%) samples from East Africans with AIDS-related symptoms, and three out of 29 (10.3%) samples from West Africans with HIV-2 infection (including a sample from an individual infected with both HIV-1 and HIV-2). Positive reactions with env-2 in these study populations were 11 out of 150 (7.3%), nine out of 60 (15%), none out of 30 (0%), 25 out of 41 (60.9%) and 29 out of 29 (100%), respectively. In the samples with dual reactivity, true versus cross-reactivity could generally be differentiated on the basis of large differences in optical density values in the respective assays. All samples reacted positively with p24/env; 308 out of 310 (99.3%) were positive in the env 1/2 assay. Four East African samples that had negative or only weakly positive reactions with env-1 showed a noticeably stronger reaction with variant peptides derived from Central African isolate sequences. In all samples from HIV-1-infected Dutch homosexual men, the strongest signal was detected using the env-1 peptide sequence, which is derived from European and American isolates., Conclusions: Small peptide antigens may permit the detection of strain-specific antibodies, allowing serological characterization of HIV isolates.

Neutralizing antibodies (NA) against HIV-1MN and HIV-1IIIB, and antibodies binding to synthetic peptides (BA) derived from the gp120 envelope V3 region principal neutralizing determinants (PND) of the HIV-1MN, HIV-1IIIB, and HIV-1Z3 virus strains were assayed in HIV-1 antibody-positive sera from the United States, Haiti, Brazil, Zaire, and Zimbabwe. The ability of soluble PND peptide to block neutralization of the corresponding virus by representative sera was also tested. In each country, NA and BA titers were highest against the HIV-1MN strain, and compared with other countries, NA and BA titers against HIV-1MN were higher in sera from the United States and Haiti. When NA titers were compared with BA titers against either HIV-1MN or HIV-1IIIB, no correlation was found for the HIV-1IIIB strain, but there was a significant correlation for HIV-1MN. Addition of the HIV-1MN strain peptide to a neutralization assay for HIV-1MN resulted in a four- to tenfold reduction in NA titers in sera from the United States, Zaire, and Brazil. The results suggest that HIV-1MN and closely related variants are prevalent in many parts of the world, and that antibodies directed against the PND account for most of the neutralizing activity in sera of infected individuals.