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Review
. 2016 Mar;37(3):221-232.
doi: 10.1016/j.it.2016.01.007. Epub 2016 Feb 9.

HIV-1 Envelope Trimer Design and Immunization Strategies To Induce Broadly Neutralizing Antibodies

Steven W de Taeye  1 , John P Moore  2 , Rogier W Sanders  3
Affiliations
Review

HIV-1 Envelope Trimer Design and Immunization Strategies To Induce Broadly Neutralizing Antibodies

Steven W de Taeye et al. Trends Immunol. 2016 Mar.

Abstract

The identification of multiple broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) trimer has facilitated its structural characterization and guided Env immunogen design. Several recent studies constitute progress in utilizing this knowledge for the development of an HIV-1 vaccine that induces bNAbs. Native-like Env trimers can induce autologous NAb responses against resistant (Tier-2) viruses in several animal models. Here we review recent studies aimed at addressing the challenge of driving the strong but narrowly focused NAb responses to Env trimers towards ones with much greater breadth. Among strategies that merit pursuing are using multiple trimers as sequential or simultaneous immunogens, targeting the germline precursors of bNAbs, delivering sequential lineages of trimers derived from infected individuals who developed bNAbs, and presenting trimers as particulate antigens.

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Figures

Figure 1
Figure 1. bNAb epitopes mapped onto the 3D structure of the BG505 SOSIP.664 trimer
The bNAbs labeled in different colors are modeled onto an EM density map of the BG505 SOSIP.664 trimer (colored in grey). The figure includes bNAbs recognizing five different epitope clusters: PG9 (V2apex), PGT122 and PGT128 (V3-glycan); PGT135 and 2G12 (OD-glycan); VRC01 (CD4bs); and PGT151, 35O22, 3BC315 and 8ANC195 (gp120-gp41 interface). Only one Fab fragment per trimer is shown for clarity. Thus, the model does not indicate the stoichiometry of bNAb binding, only the location of the epitope. This figure is an updated version of Fig.4 from Derking et al., 2015. We thank Gabe Ozorowski and Andrew Ward for preparing it.
Figure 2
Figure 2. Immunization schedules
An overview of various immunization schemes involving native-like trimers and aimed at inducing bNAbs. Displaying the trimers in particulate form (e.g., nanoparticles), and reducing their exposure of immunodominant, non-neutralizing epitopes would benefit all of these regimens.
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