Short Communication:Neutralizing Antibody Responses in Recent Seroconverters with HIV-1 Subtype C Infections in India

Abstract

The longitudinal heterologous neutralization response against two HIV-1 subtype C isolates was studied in 33 ART-naive individuals recently infected with HIV-1 subtype C from India. Seven of 33 (21%) seroconverters demonstrated a consistent response against both isolates (65-100% neutralization), whereas the remaining 26 (79%) were nonresponders. Four of the seven responders demonstrated a neutralization response (>75% neutralization) within 2-3 months of infection and in the remaining three, the response was demonstrated between 22 and 38 months after infection. In the past, HIV vaccines targeted the V3 region for the development of neutralizing antibodies. However, recent studies have shown that anti-V3 antibodies are generated after HIV-1 infection, but are not effective in neutralizing virus. In this study, the V3 sequences of HIV-1 from seven responders were analyzed and compared with those from nonresponders. The V3 region sequences from early and late responders did show certain mutations that were not found in the nonresponders; however none of these mutations could explain the neutralization responses. This suggested that HIV-1 envelope regions other than the V3 domain may be involved in generating a neutralization response. This is the first report that describes the pattern of emergence and persistence of the heterologous neutralization response in recently HIV-1 subtype C-infected individuals from India and studies its association with sequence variation in the V3 region.

Human Leukocyte Antigen Variants B*44 and B*57 Are Consistently Favorable during Two Distinct Phases of Primary HIV-1 Infection in Sub-Saharan Africans with Several Viral Subtypes

“…In the context of PHI, the acute phase does not involve intense antibody responses (19,45,67). Set-point viremia is typically reached within the first few months after infection (6), well before the debut of high-affinity neutralizing antibodies that require extensive somatic mutation (45,67).…”

“…In the context of PHI, the acute phase does not involve intense antibody responses (19,45,67). Set-point viremia is typically reached within the first few months after infection (6), well before the debut of high-affinity neutralizing antibodies that require extensive somatic mutation (45,67). The underlying immune control during acute and early chronic infection appears to depend on cellular immune pathways (8,43), including CTL and natural killer (NK) cell activities mediated by HLA class I allelic products.…”

Current Status of Research on HIV Epidemic, Pathogenesis, Management and Prevention in India

“…The results show that the neutralizing antibodies may appear early in HIV infections, but their significance in controlling early virus multiplication is not known [52]. Envelope structures from newly transmitted viruses in India are antigenically complex in spite of close genetic similarity.…”

“…The anti-HIV neutralizing antibody responses have been investigated in a small number of studies in India [52][53][54]. The results show that the neutralizing antibodies may appear early in HIV infections, but their significance in controlling early virus multiplication is not known [52].…”

Broadly Neutralizing Antibody Responses in a Subset of HIV-1-Infected Individuals in Chennai, India

“…The quantification of these broadly NAbs in distinct geographical locations may provide information that facilitates the design of a vaccine that is effective worldwide. In such an effort, it was identified 1 that the subtype “C” envelope ( env ) sequences isolated to prepare pseudoviruses from the western part of India were highly complex and that the Indian HIV-1 gp120 subtype sequence’s genetic make up was distinct from 2 subtype “C” sequences from other parts of the globe. 3 –8 Also among the Indian subtype “C” sequences, it was observed 9 –11 that there is greater sharing of neutralization determinants, which can lead to an unvarying neutralization response in most of the specimens, and this should be explored.…”