Abstract
Information about neutralizing antibody responses in subtype C-infected individuals is limited, even though this viral subtype causes the majority of AIDS cases worldwide. Here we compared the course and magnitude of the autologous neutralizing antibody (NAb) response against viral envelope (Env) glycoproteins present during acute and early infection with subtypes B and C human immunodeficiency virus type 1 (HIV-1). NAb responses were evaluated in 6 subtype B-infected and 11 subtype C-infected subjects over a mean evaluation period of 25 months using a pseudovirus reporter gene assay. All subjects in the C cohort were infected through heterosexual contact, while five of the six subjects in the B cohort were infected via male-to-male contact. The kinetics and magnitude of the NAb responses varied among subjects in the B and C cohorts; however, the median 50% inhibitory concentration (IC(50) titer) reached by antibody in the plasma of subtype C-infected subjects, overall, was 3.5-fold higher than in the subtype B-infected subjects (P = 0.06). The higher titers of NAbs in the C cohort were associated with viruses having significantly shorter amino acid length (P = 0.002) in the V1 to V4 region of the surface Env glycoprotein, gp120, compared to the B cohort. Despite the potency of the autologous subtype C NAb response, it was not directed against cross-neutralizing epitopes. These data demonstrate that subtype C Envs elicit a potent yet restricted NAb response early in infection that frequently reaches IC(50) titers in excess of 1:1,000 and suggest that clade-specific differences may exist in Env immunogenicity or susceptibility to neutralization.
Highlights
Neutralizing antibodies are likely to be an important component of vaccine-induced protective immunity
Development of the initial autologous neutralizing antibody (NAb) response was evaluated in 11 subjects infected through heterosexual contact in Zambia, 5 subjects infected through male-tomale contact in the United States, and 1 subject (FASH) presumably infected through heterosexual contact in the United States (Table 1)
We compared the course and magnitude of the autologous NAb response against Envs present during acute/ early infection in 11 subjects infected with subtype C human immunodeficiency virus type 1 (HIV-1) and 6 subjects infected with subtype B HIV-1
Summary
Neutralizing antibodies are likely to be an important component of vaccine-induced protective immunity. In HIV-1 sequences from the Los Alamos database, strong positive selection is focused on a region downstream of the third hypervariable domain (V3) of gp120 in subtype C sequences but on V3 itself in subtype B sequences [12] This finding is consistent with the V3 domain’s acting as a principal target for NAbs in subtype B infection Potent selective pressure from autologous NAbs during primary infection with subtype B HIV-1 rapidly generates viral variants that escape the initial response [2, 3, 5, 23, 27]. Unusually potent NAb responses were generated against the virus population present at seroconversion in this cohort of subtype C-infected subjects, providing new information about early subtype C infection and further highlighting potential differences between subtypes B and C. Differences in neutralization susceptibility based on viral subtype could pose further obstacles to the development of practical, widely useful vaccines
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