Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?

Env Exceptionalism: Why Are HIV-1 Env Glycoproteins Atypical Immunogens?
Cell Host Microbe. 2020 Apr 08;27(4):507-518
Authors: Klasse PJ, Ozorowski G, Sanders RW, Moore JP
Abstract
Recombinant HIV-1 envelope (Env) glycoproteins of ever-increasing sophistication have been evaluated as vaccine candidates for over 30 years. Structurally defined mimics of native trimeric Env glycoproteins (e.g., SOSIP trimers) present multiple epitopes for broadly neutralizing antibodies (bNAbs) and their germline precursors, but elicitation of bNAbs remains elusive. Here, we argue that the interactions between Env and the immune system render it exceptional among viral vaccine antigens and hinder its immunogenicity in absolute and comparative terms. In other words, Env binds to CD4 on key immune cells and transduces signals that can compromise their function. Moreover, the extensive array of oligomannose glycans on Env shields peptidic B cell epitopes, impedes the presentation of T helper cell epitopes, and attracts mannose binding proteins, which could affect the antibody response. We suggest lines of research for assessing how to overcome obstacles that the exceptional features of Env impose on the creation of a successful HIV-1 vaccine.
PMID: 32272076 [PubMed - in process]

Source: Cell Host and Microbe - April 7, 2020 Category: Microbiology Authors: Klasse PJ, Ozorowski G, Sanders RW, Moore JP Tags: Cell Host Microbe Source Type: research