High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination.
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Date
2008
Journal Title
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Publisher
Elsevier
Abstract
Identifying the earliest neutralizing antibody specificities that are elicited following infection or vaccination
by HIV-1 is an important objective of current HIV/AIDS vaccine research. We have shown previously that
transplantation of HIV-1 V3 epitopes into an HIV-2 envelope (Env) scaffold provides a sensitive and specific
means to detect and quantify HIV-1 V3 epitope specific neutralizing antibodies (Nabs) in human sera. Here,
we employ this HIV-2/HIV-1 V3 scaffolding strategy to study the kinetics of development and breadth of V3-
specific Nabs in longitudinal sera from individuals acutely infected with clade C or clade B HIV-1 and in
human subjects immunized with clade B HIV-1 immunogens. HIV-2/HIV-1 chimeras containing V3
sequences matched to virus type (HIV-2 or HIV-1), subtype (clade B or C), or strain (autologous or
heterologous) were used as test reagents. We found that by 3–8 weeks post infection, 12 of 14 clade C
subjects had a median IC50 V3-specific Nab titer of 1:700 against chimeric viruses containing a heterologous
clade C V3. By 5 months post-infection, all 14 subjects were positive for V3-specific Nabs with median titers
of 1:8000 against heterologous clade C V3 and 1:1300 against clade B V3. Two acutely infected clade B
patients developed heterologous clade B V3-specific Nabs at titers of 1:300 and 1:1800 by 13 weeks of
infection and 1:5000 and 1:11000 by 7 months of infection. Titers were not different against chimeras
containing autologous clade B V3 sequences. Each of 10 uninfected normal human volunteers who were
immunized with clade B HIV-1 Env immunogens, but none of five sham immunized control subjects,
developed V3-specific Nabs titers as high as 1:3000 (median 1:1300; range 1:700–1:3000). None of the HIV-
1 infected or vaccinated subjects had antibodies that neutralized primary HIV-1 virus strains. These results
indicate that high-titer, broadly reactive V3-specific antibodies are among the first to be elicited during acute
and early HIV-1 infection and following vaccination but these antibodies lack neutralizing potency against
primary HIV-1 viruses, which effectively shield V3 from antibody binding to the functional Env trimer.
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Citation
Davis, K.L., Gray, E.S., Moore, P.L., et al. 2009. High titer HIV-1 V3-specific antibodies with broad reactivity but low neutralizing potency in acute infection and following vaccination. Virology. 387, pp. 414–426.