Volume 9 Supplement 2
Refined identification of neutralization-resistant CRF02_AG viruses and their sensitivity to anti-MPER neutralizing antibodies
© Jacob et al; licensee BioMed Central Ltd. 2012
Published: 13 September 2012
The first antibody-inducing HIV-1 vaccines are unlikely to protect against all HIV-1 isolates. There is thus a danger that a vaccine will select for HIV-1 viruses that are highly resistant to antibody-mediated neutralization. We sought to identify and characterize such viruses.
A diverse panel of 24 HIV-1 pseudoviruses was tested for neutralization resistance using two sets of samples from ARV-naive HIV-1-infected individuals selected for good neutralizers: sera from South Africa donors (n=68, infected >1 year, subtype C predominant area) and CRF02_AG-infected plasma samples from Cameroon donors (n=12, good neutralizers selected from 22 samples).
Sensitivity to South Africa sera by subtype was C>B≈CRF02_AG>A. Importantly, and in contrast to previous reports, CRF02_AG plasma neutralized CRF02_AG viruses better than other panel viruses (“within-subtype neutralization”). This included three (257-31, 251-18 and 33-7) of five CRF02_AG viruses previously designated as tier 3 (most resistant). This within-subtype neutralization testing showed that the other two tier 3 CRF02_AG panel viruses, 253-11 and 278-50 were highly resistant. Most CRF02_AG viruses, including 253-11 and 278-50 were sensitive to two membrane proximal external region (MPER)-specific monoclonal antibodies and soluble CD4 (sCD4), suggesting targets for neutralization of even these highly resistant viruses. This information may help design a global HIV-1 vaccine. We also propose testing viruses with within-subtype samples selected for good neutralizers in order to evaluate their neutralization resistance.
Some but not all CRF02_AG viruses are sensitive to neutralisation by CRF02_AG-derived plasma, even though most are previously reported as highly resistant (Tier 3). Further work is necessary to properly characterize such Tier 3 viruses. If research focus is not placed on such resistant viruses, a future partially effective HIV-1 vaccine may select for them.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.