Anti-V2 Antibody Deficiency in Individuals Infected With HIV-1

ABSTRACTThe positive correlation of high levels of plasma anti-V2 antibodies (Abs) with protective immunity in the Phase III anti-HIV RV144 vaccine trial generated interest in the induction of these Abs for HIV vaccine development. We analyzed plasma samples from 79 chronically infected Cameroonian individuals for Ab reactivity against three V1V2 fusion proteins and five cyclic V2 peptides and found that HIV-1 infection induces different levels of anti-V2 Abs. While the majority of plasma samples reacted strongly with one or more V2 antigens, 10% (8) of the samples were nonreactive. Deficiency of anti-V2 Abs was consistently found in longitudinal plasma samples tested over 8 to 54 months of HIV infection. There was a strong correlation between binding activities of plasma anti-V2 Abs and anti-gp120 and anti-gp41 Abs, suggesting that deficiency of V2 Abs could be related, in part, to a limited ability to elicit strong Ab responses. Analysis of gp120 sequences revealed that the V2 region of viruses from donors with V2-deficient versus V2-reactive Abs displayed a tendency toward longer length, more glycans, and lower isoelectric point and charge. No differences between these two patient groups were noted in the same parameters measured in the V1 region. These data suggest that immunogens containing a shorter V2 region with fewer glycosylation sites and higher electrostatic charges would be beneficial for induction of anti-V2 Abs, but the ability to mount a strong general Ab response to HIV-1 appears to be a dominant factor.IMPORTANCEThe results of the RV144 vaccine clinical trial showed a correlation between plasma Abs against a V1V2 fusion protein and a decreased risk of acquiring HIV-1 infection. This turned the focus of some HIV vaccine design to the induction of elevated levels of anti-V2 Abs to increase vaccine efficacy. In plasma samples from Cameroonian individuals infected with HIV-1, we observed broad variations in levels of anti-V2 Abs, and 8 of the 79 plasma samples tested displayed substantial deficiency of V2 Abs. Sequence analysis of the V2 region from plasma viruses and multivariate analyses of V2 characteristics showed a significant difference in several features between V2-deficient and V2-reactive plasma Abs. These results suggest that HIV vaccine immunogens containing a V2 region with shorter length, fewer glycosylation sites, and higher electrostatic charges may be beneficial for induction of a higher level of anti-V2 Abs and thus contribute to HIV vaccine efficacy.