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- Open Access
Heterologous neutralization breadth persists despite B-lymphocyte dysfunction in chronic HIV-1 infection
© Murphy et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Immune Activation
- Plasma Viral Load
- Neutralize Activity
- Lower Dilution
- Pseudotyped Virion
Of the millions globally infected with HIV-1, only 20-30% will develop broadly neutralizing antibodies. To date, no one has measured this phenomenon in a cohort of subjects for which multiple aspects of B-lymphocyte dysfunction have been evaluated in parallel.
In 16 viremic seroconverters, the cross-clade neutralizing activity of plasma was investigated using a panel of thirteen clade A, B, and C HIV-1 envelope (Env) pseudotyped virions, which represented three tiers of sensitivity. The neutralization IC50 was calculated for each plasma-Env combination, and these data were used to determine a breadth (how many Envs were neutralized) and potency (the strength of neutralization) score for each seroconverter. Additionally, the level of plasma antibodies that bound to the monomeric form of a subtype B Env gp120 (HIV-1 BaL) was quantitated.
A range of neutralization breadth emerged: three plasma samples (19%) demonstrated widespread neutralizing activity against this panel of Envs, while five subjects (31%) exhibited a complete lack of detectable neutralization at the lowest dilution of plasma tested (1:100). No correlation was observed between neutralization breadth or potency and parameters of B-lymphocyte dysfunction (PD-1, BTLA), immune activation (Ki-67, CD95), or disease progression (CD4 T cell count, plasma viral load). The level of total IgG in each plasma sample, however, did significantly correlate with both neutralization breadth and potency. Like total IgG, anti-gp120 binding antibodies also positively correlated, but, in this case, the correlations only trended toward significance. Anti-gp120 binding antibodies did not correlate with parameters of B-lymphocyte dysfunction, immune activation, disease progression, or total IgG level.
These findings demonstrate that even in chronically HIV-1-infected subjects in whom B-lymphocytes display multiple indications of dysfunction, antibodies that mediate cross-clade neutralization breadth (particularly anti-gp120 binding and other IgG antibody specificities) continue to circulate in plasma.
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.