Analysis of HIV antibodies provides further insight into immune escape, potential vaccine

Chung AW. Proc Natl Acad Sci U S A. 2011;108:7505-7510.

Antibody-dependent cellular cytotoxicity antibodies applied pressure on the HIV virus but failed to recognize the concurrent HIV sequence in a series of epitopes, according to study results.

The role of antibody-dependent cellular cytotoxicity in controlling HIV is not fully understood, according to a group of researchers from Australia. The current study examined whether pressure from antibody-dependent cellular cytotoxicity antibodies specific to HIV would result in immune-escape variants.

Eighty patients with no antiretroviral therapy experience and 12 patients with resistant HIV disease were initially recruited from the Melbourne Sexual Health Centre and the Alfred Hospital in Australia.

The final analysis involved samples from 22 patients that were used to map a series of 59 antibody-dependent cellular cytotoxicity epitopes using a flow cytometric assay. The researchers cloned and sequenced strains of HIV across relevant epitopes. Plasma samples yielding positive responses to peptide pools spanning whole proteins were tested against subpools of 30 peptides to further narrow the location of the epitope.

Plasma samples from those individuals that activated more than 1% of natural killer cells in response to the subpools were mapped to individual linear 15-mer peptides, according to the results.

The researchers identified 57 epitopes in Env and three epitopes in Vpu. They compared the antibody responses to the same peptide epitope derived from the concurrent HIV sequences expressed in circulating virus.

The antibody-dependent cellular cytotoxicity antibodies failed to recognize the concurrent HIV sequence in nine of 13 epitopes studied. The researchers suggested that these responses apply immune pressure on the virus, a result which may have implications for the induction of responses by potential HIV vaccines.

“This report provides evidence that nonneutralizing [antibody-dependent cellular cytotoxicity] antibodies can force HIV escape mutations,” the researchers wrote. “On the one hand, this result provides evidence of the pressure applied by [antibody-dependent cellular cytotoxicity] antibodies. On the other hand, however, it presents challenges in inducing the most effective [antibody-dependent cellular cytotoxicity] antibodies by vaccination.”

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