Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States.

Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa. In this study, the neutralization profiles of contemporary subtype B Envs from the U.S. were assessed to characterize changes in neutralization sensitivities over time. We generated a panel of 30 contemporary pseudoviruses (PSVs) and demonstrated continued diversification of subtype B Env from the 1980s up to 2018. Neutralization sensitivities of the contemporary subtype B PSVs were characterized using 31 neutralizing antibodies (NAbs) and were compared with strains from earlier in the HIV-1 pandemic. A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 NAbs for the contemporary as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the NAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A meta-analysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1. Author summary: HIV-1 has evolved and diversified over the last forty years of the pandemic. These changes have shifted viral properties in such a way that the effectiveness of current therapeutic HIV-specific broadly neutralizing antibodies may be reduced over time. Understanding these changes will allow for the development of improved vaccine and antibody products. In this study, we generated a panel of 30 HIV-1 strains from the United States from samples collected between 2017 and 2018. We characterized the sensitivity of these contemporary HIV-1 strains using 31 antibodies that can inhibit, or neutralize, infection and compared the results to those of viruses from earlier in the pandemic. Our results show that antibodies that were effective against HIV-1 strains from earlier in the pandemic are not as effective against current HIV-1 strains. This trend in reduced sensitivity over time is occurring globally, as similar results were observed in Thailand and Africa. These results will inform the development of more effective antibodies and vaccines to elicit them. [ABSTRACT FROM AUTHOR]