Profiles of neutralizing antibody response in chronically human immunodeficiency virus type 1 clade B′-infected former plasma donors from China naive to antiretroviral therapy

Broadly neutralizing antibodies (NAbs) such as those generated in chronic human immunodeficiency virus type 1 (HIV-1) infection are considered a key component for an effective HIV-1 vaccine. Here, we measured NAb responses using a panel of 25 Env-pseudotyped viruses, including clade B, C, A, CRF07_BC and CRF01_AE strains, against plasma samples from 103 subjects in a former plasma donor cohort in central China, who were infected with HIV-1 clade B' for at least 10 years and naive to antiretroviral therapy at the time of sampling. We found that 64 % of samples (n=66) neutralized at least half of the viruses tested and 2% (n=2) neutralized all of the viruses, while 5% (n=5) neutralized none of the viruses tested. Strikingly, 29% of plasma samples (n=30) neutralized >80% of the viral strains tested, indicating the presence of broadly reactive NAbs in these patients. When the magnitude (geometric mean 1050 titres, GMTs) or breadth of neutralization was assessed for correlation with CD4 count or plasma viral load, the only significant positive correlations were observed between viral load and neutralization magnitude (r=0.2189, P=0.0263) and between viral load and neutralization breadth (r=0.1970, P=0.0461). A moderate difference between progressors and long-term non-progressors was observed in both the breadth (P=0.0316) and the potency (P=0.0300). A significant difference was found in the GMTs between intra-clade and inter-clade strains (P<0.001). Heat-map analysis based on k-means clustering of plasma determined a statistically stable cluster of plasma with cross-reactive and potent neutralizing reactivity. These samples could provide physical biomaterials for further virological and serological studies from which useful insights into rational HIV-1 vaccine development and therapeutic design might be derived.