Epitope specificity of cross-clade neutralizing sera from Chinese HIV-1-positive individuals

Induction of broadly neutralizing antibody is considered important for an effective HIV-1 vaccine. Identification and characterization of broadly neutralizing antibodies in HIV-1-infected patients will facilitate our understanding of the immune correlates to protection and the design of an effective prophylactic vaccine. A number of studies to probe the specificity of antibodies in broadly neutralizing sera in the United States and Europe have been reported. However, little is known about and would be interesting to investigate the immunological characteristics of HIV-1-positive sera in China where non-clade B viruses are prevalent and the circulating viral subtypes are distinct and more complex than both the United States and Europe. Here, we screened 80 Chinese HIV-1-positive sera against a minipanel of pseudoviruses representing various circulating HIV-1 subtypes in China and identified 8 cross-clade neutralizing sera (CNsera). Immunological characterization of the sera showed that gp120-targeting antibodies with multiple epitope specificities contributed to the cross-clade neutralizing activity of these CNsera. V3-directed antibodies were prevalent in these CNsera, but did not mainly contribute to their neutralization breath and potency while CD4bs-specific, 2F5- and 4E10-like antibodies were rarely detected. 2G12-like neutralizing antibodies were more frequently detected in HIV-1 patients from China where recombinant subtype viruses are prevalent than in United States and Europe. One broadly neutralizing serum (Serum 45) was identified to contain antibodies with unknown epitope specificities that were sensitive to terminal glycan modifications on virus Env and insensitive to N160K mutagenesis, and correlated with the cross-clade neutralization activity of Serum 45.