Neutralizing and non-neutralizing antibody responses in HIV-1 subtype C chronically infected patients with divergent rates of disease progression
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KeywordsSlow Progressors Amino Acid Length Diverse Panel Divergent Rate IC50 Titer
Development of an efficacious HIV-1 vaccine able to elicit the production of broadly neutralizing antibodies (nAbs), capable of retaining potent activity against a diverse panel of viral isolates remains a significant challenge. The evolutionary forces that shape envelope and ensuing nAb and non-neutralizing antibodies in HIV-1 subtype C are incompletely understood and these two parameters have been rarely studied concurrently.
We characterized patterns of virus-specific nAbs and non-neutralizing antibodies in four slow progressors and four progressors with chronic HIV-1 subtype C infection, over a median of 21 months. Single cycle neutralization assays was performed. In addition, the binding affinities of HIV-specific immunoglobulins (IgGs) and the affinities of the IgGs to various Fcγ receptors (FcγRs) were assessed.
NAbs evolved significantly in progressors (p=0.003) from study entry to study exit. NAb IC50 titers significantly correlated with amino acid lengths for V1-V2 (p=0.04), C3-V5 (p=0.03) and V1-V5 (p=0.04). Both groups displayed preferential heterologous activity against the subtype C panel. Both groups displayed preferential heterologous activity against the subtype C panel. There were no significant differences in breadth of responses between the groups for either subtype A or C. Neutralization breadth and titers to subtype B reference strains was significantly higher in progressors compared to slow progressors (both p<0.03) with increasing nAb breadth from study entry to study exit in progressors. Progressors had cross-reactive neutralizing antibodies that targeted V2 and V3. Binding affinities of non-neutralizing antibodies to HIV-specific gp120, gp41 and p24 and to activating and inhibitory Fcγ receptors (FcγRs) were similar in both groups. However, in slow progressors, CD4 T-cell counts correlated inversely with antibody binding affinity for the activating FcγRIIa (p=0.005).
Overall, the data suggest that neither nAbs nor non-neutralizing antibodies could be directly associated with disease attenuation. However, continuous evolution of nAbs was a potential marker of disease progression.
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.