HIV-1 Env Does Not Enable the Development of Protective Broadly Neutralizing Antibodies in an Experimental Autoimmune Encephalomyelitis Mouse Model.

Gabriel Siracusano,Vittorio Martinelli,Annamaria Finardi,Roberto Furlan,Claudia Pastori,Lucia Lopalco

doi:10.3389/fimmu.2021.771359

Abstract

Recent studies showed that immunological tolerance may restrict the development of Env-specific autoreactive broadly neutralizing antibodies. This evidence is consistent with the finding that Env immunization of a systemic lupus erythematosus (SLE) murine model produced antibodies that neutralize tier 2 HIV-1 strains. In this study, we address the possibility of eliciting neutralizing anti-Env antibodies in other autoimmune diseases such as multiple sclerosis (MS). While, as reported for SLE, we showed for the first time that a small number of HIV-1 negative, relapsing remitting MS patients exhibited antibodies with neutralizing properties, our attempts at inducing those antibodies in a EAE mouse model of MS failed. The success in eliciting Env-specific neutralizing antibodies might be related to the specific characteristics of the autoimmune disease, or it might rely in improving the vaccination design. Studies using mouse models are useful to gain insight in how HIV-specific neutralizing antibody responses are regulated in order to develop a protective HIV-1 vaccine.

Highlights

HIV-1, the causative agent of the acquired immunodeficiency syndrome (AIDS), is a global public health problem accounting for the infection of almost 40 million people worldwide [1]
Based on previously published findings [1], we wondered whether the production of bnAbs was restricted to systemic lupus erythematosus (SLE) patients and its relative mouse models, or bnAbs were developed in other autoimmune diseases as well, such as multiple sclerosis (MS)
Autoreactive B cells are subjected to negative selection in the bone marrow, where they are eliminated or silenced by mechanisms of central tolerance

Summary

Introduction

HIV-1, the causative agent of the acquired immunodeficiency syndrome (AIDS), is a global public health problem accounting for the infection of almost 40 million people worldwide [1]. 10-20% of HIV-1-infected subjects develop potent and specific broadly neutralizing antibodies (bnAbs) able to neutralize the 90% of the circulating HIV-1 strains but only 1-2 years after primary infection These Abs recognize several conserved and less immunogenic neutralizing epitopes of the HIV-1 envelope (Env) protein complex, including the gp120 CD4 binding site (CD4bs), gp membrane-proximal external region (MPER), gp120 V1/V2 loop, gp120 V3-glycans [2, 3]. The elicitation of such antibodies is one of the main challenges for the development of HIV-1 vaccine candidates. Interesting evidences come from epidemiologic studies the frequency of HIV-1 infection in subjects affected SLE is very low [13, 16,17,18], and a SLE patient harbored plasma able to neutralize a wide breadth of HIV-1 strains and to control HIV-1 infection in the absence of antiretroviral therapy [5]

Methods

Results

Conclusion