Lower Broadly Neutralizing Antibody Responses in Female Versus Male HIV-1 Infected Injecting Drug Users.

Zelda Euler,Alexandra Trkola,Tom L Van Den Kerkhof,Rogier W Sanders,Roger D Kouyos,Todd M Allen,Damien C Tully,Marit J Van Gils,Hanneke Schuitemaker

doi:10.3390/v11040384

Abstract

Understanding the factors involved in the development of broadly neutralizing antibody (bNAb) responses in natural infection can guide vaccine design aimed at eliciting protective bNAb responses. Most of the studies to identify and study the development of bNAb responses have been performed in individuals who had become infected via homo- or heterosexual HIV-1 transmission; however, the prevalence and characteristics of bNAb responses in injecting drug users (IDUs) have been underrepresented. We retrospectively studied the prevalence of bNAb responses in HIV-1 infected individuals in the Amsterdam Cohort, including 50 male and 35 female participants who reported injecting drug use as the only risk factor. Our study revealed a significantly lower prevalence of bNAb responses in females compared to males. Gender, transmission route and CD4+ count at set point, but not viral load, were independently associated with the development of bNAb responses in IDUs. To further explore the influences of gender in the setting of IDU, we also looked into the Swiss 4.5k Screen. There we observed lower bNAb responses in female IDUs as well. These results reveal that the emergence of bNAbs may be dependent on multiple factors, including gender. Therefore, the effect of gender on the development of bNAb responses is a factor that should be taken into account when designing vaccine efficacy trials.

Highlights

An effective HIV-1 vaccine should be capable of eliciting broadly neutralizing antibodies, defined as the ability to neutralize various heterologous viruses from different subtypes, in order to Viruses 2019, 11, 384; doi:10.3390/v11040384 www.mdpi.com/journal/virusesViruses 2019, 11, 384 provide protection against HIV-1 acquisition [1,2,3]
In analogy to the studies using the Amsterdam Cohort, we focused in this analysis on MSM and injecting drug users (IDUs)
The results indicate that broadly neutralizing antibodies (bNAbs) in IDUs had it may point at possible multiple virus transmission (MVT) in the IDUs (Figure 2C)

Summary

Introduction

An effective HIV-1 vaccine should be capable of eliciting broadly neutralizing antibodies (bNAbs), defined as the ability to neutralize various heterologous viruses from different subtypes, in order to Viruses 2019, 11, 384; doi:10.3390/v11040384 www.mdpi.com/journal/virusesViruses 2019, 11, 384 provide protection against HIV-1 acquisition [1,2,3]. During HIV-1 infection, neutralizing antibodies (NAbs) develop within the first three months of infection [4,5]. These NAbs are usually strain-specific and the autologous virus can rapidly escape from them. 1% of the HIV-1 infected individuals, termed “elite neutralizers”, develop bNAbs that neutralize the majority of HIV-1 subtypes with very high breadth and potency [8,9,12,14,15]. BNAbs do not protect from disease progression, the passive transfer of bNAbs can completely block infection by a chimeric simian–human immunodeficiency virus (SHIV) in nonhuman primate studies [18,19,20,21,22,23,24] and reduce viral load in chronically infected humans and macaques [25,26,27,28,29].

Methods

Discussion

Conclusion