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

Abstract

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.

Genetic signatures in the highly virulent subtype B HIV-1 conferring immune escape to V1/V2 and V3 broadly neutralizing antibodies

“…The deletion in V2 did not impact virus sensitivity to bNAbs targeting the V3 and the CD4 binding site (Figure 3B). The four VB variants we investigated showed similar level of neutralization sensitivity to the CD4 binding site bNAbs VRC01, 3BNC177, and NIH45-46 as compared to the contemporary subtype B viruses reported in a recent study 12 .…”

Differences in neutralizing antibody sensitivities and envelope characteristics indicate distinct antigenic properties of Nigerian HIV-1 subtype G and CRF02_AG

“…The tri-specific NmAb therapeutic approach may improve coverage against distinct HIV-1 subtypes. Another observation for NmAbs that has been made by several groups, including ours [ 54 ] is the increasing resistance of more contemporary viruses to several NmAbs over the decades of the epidemic. In our present study, we used the available samples from chronic infection within the available cohorts in Nigeria.…”