Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection.
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Date
2009
Journal Title
Journal ISSN
Volume Title
Publisher
Plos
Abstract
We previously showed that HIV-1 subtype C viruses elicit potent but highly type-specific neutralizing antibodies (nAb)
within the first year of infection. In order to determine the specificity and evolution of these autologous nAbs, we examined
neutralization escape in four individuals whose responses against the earliest envelope differed in magnitude and potency.
Neutralization escape occurred in all participants, with later viruses showing decreased sensitivity to contemporaneous sera,
although they retained sensitivity to new nAb responses. Early nAb responses were very restricted, occurring sequentially
and targeting only two regions of the envelope. In V1V2, limited amino acid changes often involving indels or glycans,
mediated partial or complete escape, with nAbs targeting the V1V2 region directly in 2 cases. The alpha-2 helix of C3 was
also a nAb target, with neutralization escape associated with changes to positively charged residues. In one individual,
relatively high titers of anti-C3 nAbs were required to drive genetic escape, taking up to 7 weeks for the resistant variant to
predominate. Thereafter titers waned but were still measurable. Development of this single anti-C3 nAb specificity was
associated with a 7-fold drop in HIV-1 viral load and a 4-fold rebound as the escape mutation emerged. Overall, our data
suggest the development of a very limited number of neutralizing antibody specificities during the early stages of HIV-1
subtype C infection, with temporal fluctuations in specificities as escape occurs. While the mechanism of neutralization
escape appears to vary between individuals, the involvement of limited regions suggests there might be common
vulnerabilities in the HIV-1 subtype C transmitted envelope.
Description
Keywords
HIV infections--Immunology.
Citation
Moore P.L., Ranchobe N., Lambson B.E., Gray E.S., Cave E., et al. 2009. Limited Neutralizing Antibody Specificities Drive Neutralization Escape in Early HIV-1 Subtype C Infection. PLoS Pathog 5(9), pp. 1-13.