Abstract
Although a number of standardized human immunodeficiency virus 1 (HIV-1) pseudoviruses have been generated to assess neutralizing antibodies, subtype B/B′ has not been comprehensively characterized either genotypically or phenotypically. Full-length env genes were isolated from plasma samples derived from B/B′-infected individuals, including former plasma donors and men who had sex with men. The neutralization properties of these pseudoviruses were determined by testing against sCD4, 16 neutralizing monoclonal antibodies and 44 plasma samples, including samples from those infected with the three major prevalent clades in China. Twenty-eight pseudoviruses were successfully constructed, including 15 B′ and 13 B strains. Compared with subtype B strains from North America and Europe, the B′ strains from China showed greater variation in the V3 loop and higher susceptibility to the neutralizing antibody 2F5 and B/B′ plasma samples. The B′ strains from China showed significantly lower susceptibility to some trimer apex-binding neutralizing antibodies (PGT145, CH01, CH02, CH03, and CH04) than the B strains from Western countries. The 28 B-pseudotyped and B′-pseudotyped viruses were grouped into high, medium, and low clusters based on their overall neutralization sensitivity to plasma samples. The different genotypic and phenotypic properties of the standard subtype B from those of the Western viruses compared to the B and B′ strains from China suggest that clones from HIV-1-infected individuals in China are more suitable for the evaluation of candidate vaccines targeting the subtype B/B′ viruses circulating in China.
Highlights
It is widely accepted that neutralizing antibodies (NAbs) play a key role in the efficacy of most currently used vaccines against viruses, such as those that cause smallpox and measles, polio, influenza, rabies, and human papillomavirus[1]
Since the identification of HIV as the causative agent of acquired immunodeficiency syndrome (AIDS), a wide range of assays have been used to evaluate NAbs for the development of candidate vaccines, including T cell lines infected with T cell-line-adapted viruses, peripheral blood mononuclear cells infected with primary isolated viruses, and engineered cell lines infected with pseudoviruses or recombinant infectious viruses[11,12,13,14,15,16,17,18]
Of the 28 isolates originating from China, 15 were grouped as clade B′, all of which were derived from former plasma donors (FPDs)
Summary
It is widely accepted that neutralizing antibodies (NAbs) play a key role in the efficacy of most currently used vaccines against viruses, such as those that cause smallpox and measles, polio, influenza, rabies, and human papillomavirus[1]. Since the identification of HIV as the causative agent of acquired immunodeficiency syndrome (AIDS), a wide range of assays have been used to evaluate NAbs for the development of candidate vaccines, including T cell lines infected with T cell-line-adapted viruses, peripheral blood mononuclear cells infected with primary isolated viruses, and engineered cell lines infected with pseudoviruses or recombinant infectious viruses[11,12,13,14,15,16,17,18] Of these methods, the pseudovirus-based neutralization assay (PBNA) using. One of the greatest advantages of a PBNA based on TZM-bl is the high versatility of the viral strains, which can be achieved by replacing the envexpressing plasmid with another plasmid in the transfection phase to generate a pseudovirus with the expected env protein on its surface
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