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Breadth and Magnitude of envelope-specific ADCC responses in people who naturally control HIV

Breadth and Magnitude of envelope-specific ADCC responses in people who naturally control HIV

People who naturally control HIV infection (slow progressors and viremic controllers) provide important insights into the immune correlates of protection against HIV. Understanding such immune correlates is vital to designing a vaccine against HIV. Both magnitude and breadth of protective immune responses are considered important in producing an effective, globally relevant HIV vaccine.

In trying to identify these immune responses, scientific endeavour has focused on antibody dependent cellular cytotoxicity (ADCC) as a novel HIV vaccine modality, after vaccine strategies based on neutralizing antibodies and T-cell immunity failed to demonstrate efficacy.
We studied ADCC immune responses to envelope glycoprotein subtypes A, B, BC, C, D, E and F using our previously described ADCC ICS assay in 15 people who naturally control their HIV infection (controllers) and compared this with 15 HIV subjects with progressive HIV infection (progressors). Controllers were subjects with CD4 >400 cells/ul, 7 or more years after diagnosis and/or with persistently low (<3000 copies/ml) or fully suppressed plasma viral loads. The magnitude was measured in terms of NK cell expression of CD107a+IFNg+ (<2%=low; 2-8%=medium and >8%=strong responses).

ADCC responses in controllers were higher than in progressors (medium to strong responses in 100% vs 53%; p <0.01). ADCC Ab responses were broader in HIV controllers (93% had cross reactivity to at least one subtype) than in HIV progressors (53%; p<0.01)). We also observed that the ADCC responses were higher to HIV-1 gp120 than gp140. Furthermore, we demonstrated that glycosylated envelope proteins elicit potent ADCC response and that responses to gp120 are higher than gp140.
The potency and breadth of ADCC responses that we have detected to envelope proteins in people who naturally control HIV infection may provide important insights into both prophylactic and therapeutic rational HIV vaccine design. Strong responses to gp120 may indicate hidden epitopes, not exposed in trimeric gp140. Strong responses to glycosylated envelope proteins suggest that glycolsylation is not dampening these responses.

Speakers: Dr Ivan Stratov
Conference: ASHM 2013
Areas of Interest / Categories: AIDS 2013

AIDS 2013

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