Antibody Recognition of CD4-Induced Open HIV-1 Env Trimers

Abstract

The RV144 HIV-1 clinical vaccination trial showed modest protection against viral infection. Antibody responses to the V1V2 region of HIV-1 Env gp120 were correlated inversely with the risk of infection, and data from three other clinical vaccine trials suggested a similar signal.

A Germline-Targeting Chimpanzee SIV Envelope Glycoprotein Elicits a New Class of V2-Apex Directed Cross-Neutralizing Antibodies

“…To determine whether the CAM13K and CAM13RRK Envs inherently adopt a more open conformation, we tested their sensitivity to conformation-sensitive V2i (697-D, 1393A) ( 62 ), V2p (CH58, CAP228-3D) ( 42 , 63 , 64 ), linear V3 (3074, 447-52D) ( 65 , 66 ), and CD4i (17b, A32) ( 67 , 68 ) antibodies as well as the V2-apex bNAb PG9 for control. These antibodies were selected because they recognize epitopes that are occluded in prefusion trimers and thus only neutralize viruses whose Envs are incompletely closed.…”

Optimal Expression, Function, and Immunogenicity of an HIV-1 Vaccine Derived from the Approved Ebola Vaccine, rVSV-ZEBOV

“…Previous studies reveal that an Env immunogen functional for receptor binding and host-cell entry may have a higher probability of inducing effective anti-HIV immune responses [ 46 , 49 , 50 ]. The surface expression of the Env chimeras is detected with the anti-B12 gp120 antibody on the majority of transfected HeLa cells ( Figure 3 A).…”

“…The ability of an HIV-1 Env immunogen to elicit protective anti-Env antibody responses requires a trimeric Env structure, preferably associated with a viral membrane that mimics the native HIV-1 Env structure [ 46 , 49 , 50 , 53 ]. Improved immunogenicity could also relate to an HIV-1 Env trimer binding its receptor/co-receptor and possibly exposing hidden, conserved Env epitopes for antigen presentation and immune recognition/response [ 49 , 50 , 54 ]. The function of the chimeric A74 Envs has to be analyzed independent of the rVSV-ZEBOV due to the co-expression of EBOV_GP.…”