Broadly neutralizing plasma antibodies effective against autologous circulating viruses in infants with multivariant HIV-1 infection

Nitesh Mishra,Rakesh Lodha,Ayushman Dobhal,Himanshi Chawla,Sanjeev Kumar,Bimal Kumar Das,Ravinder Singh,Kalpana Luthra,Shaifali Sharma,Sushil Kumar Kabra,Muzamil Ashraf Makhdoomi

doi:10.1038/s41467-020-18225-x

Abstract

Broadly neutralizing antibodies (bnAbs) develop in a subset of HIV-1 infected individuals over 2–3 years of infection. Infected infants develop plasma bnAbs frequently and as early as 1-year post-infection suggesting factors governing bnAb induction in infants are distinct from adults. Understanding viral characteristics in infected infants with early bnAb responses will provide key information about antigenic triggers driving B cell maturation pathways towards induction of bnAbs. Herein, we evaluate the presence of plasma bnAbs in a cohort of 51 HIV-1 clade-C infected infants and identify viral factors associated with early bnAb responses. Plasma bnAbs targeting V2-apex on the env are predominant in infant elite and broad neutralizers. Circulating viral variants in infant elite neutralizers are susceptible to V2-apex bnAbs. In infant elite neutralizers, multivariant infection is associated with plasma bnAbs targeting diverse autologous viruses. Our data provides information supportive of polyvalent vaccination approaches capable of inducing V2-apex bnAbs against HIV-1.

Highlights

Neutralizing antibodies develop in a subset of human immunodeficiency virus-1 (HIV-1) infected individuals over 2–3 years of infection
HIV-1 bnAbs are categorized based on their recognition of five distinct and largely conserved epitopes on the envelope spike that are promising vaccine targets: the N160 glycan located within the V2 loop at the trimer apex (V2-apex), high mannose patch centered around N332 in the V3 region, the CD4 binding site (CD4bs), the membrane-proximal external region (MPER), and the N-glycans located at the gp120–gp[41] interface[1,2]
Infants infected via mother-to-child transmission (MTCT), with the well-defined genetic bottleneck leading to infection with a minor variant[23], provide a unique setting to understand the viral factors associated with induction of bnAbs

Summary

Introduction

Neutralizing antibodies (bnAbs) develop in a subset of HIV-1 infected individuals over 2–3 years of infection. Understanding viral characteristics in infected infants with early bnAb responses will provide key information about antigenic triggers driving B cell maturation pathways towards induction of bnAbs. we evaluate the presence of plasma bnAbs in a cohort of 51 HIV-1 clade-C infected infants and identify viral factors associated with early bnAb responses. Studies undertaken in infants have, documented that HIV-1 infected infants develop potent plasma bnAbs as early as one-year post-infection[17,18] suggesting that an effective vaccine in infants may perhaps be able to trigger the immune system and elicit an early bnAb response providing an impetus to evaluate the antibody response in a cohort of perinatally infected infants. We evaluate the characteristic features of circulating viral strains in infants that show an early bnAb response to understand the antigenic triggers that drive B cell maturation pathways toward the induction of bnAbs

Methods

Results

Conclusion