Cross-reactive broadly neutralizing antibodies: timing is everything

Zelda Euler,Hanneke Schuitemaker

doi:10.3389/fimmu.2012.00215

Abstract

The recent surge of research into new broadly neutralizing antibodies in HIV-1 infection has recharged the field of HIV-1 vaccinology. In this review we discuss the currently known broadly neutralizing antibodies and focus on factors that may shape these antibodies in natural infection. We further discuss the role of these antibodies in the clinical course of the infection and consider immunological obstacles in inducing broadly neutralizing antibodies with a vaccine.

Highlights

Thirty years after the discovery of HIV, UNAIDS estimates 34 million people are living with HIV and nearly 30 million people have died of AIDS-related causes since the first case of AIDS was reported on 5 June 1981
In a recent genome wide association study (GWAS) on the development of cross-reactive neutralizing activity (CrNA), we have found several single nucleotide polymorphisms (SNPs) in the gene region of MHC class I chainrelated protein A (MICA) on chromosome 6 that were associated with the development of CrNA at 3 years post-serconversion (Euler et al, submitted for publication)
In a recent study we have revealed an association between CrNA in serum and the presence, in the first year of infection, of HIV-1 variants with envelopes that had a shorter V1 region and a lower NXS/NXT ratio, the latter indicating fewer potential Nlinked glycosylation sites (PNGS)

Summary

INTRODUCTION

Thirty years after the discovery of HIV, UNAIDS estimates 34 million people are living with HIV and nearly 30 million people have died of AIDS-related causes since the first case of AIDS was reported on 5 June 1981 (www.unaids.org; Centers for Disease Control, 1981). The RV144 HIV vaccine trial was, the first to show some modest efficacy against acquisition of infection (Rerks-Ngarm et al, 2009) In this trial protection against infection was associated with antibodies directed against the second variable (V2) domain in the envelope of HIV. Recent studies in the field have shown that broadly neutralizing antibodies may be more prevalent in HIV-1 infection than previously considered and these antibodies seem to have varying epitope specificities that could allow for multidirectional vaccine design. NEUTRALIZING ANTIBODIES TO HIV-1 The first detectable antibodies directed against the HIV-1 envelope appear around 12 days after infection These antibodies are non-neutralizing, directed against the gp region, and mainly forming immune complexes (Tomaras and Haynes, 2009; Figure 1).

Euler and Schuitemaker

Findings

CONCLUSION