Analysis of Complement-Mediated Lysis of Simian Immunodeficiency Virus (SIV) and SIV-Infected Cells Reveals Sex Differences in Vaccine-Induced Immune Responses in Rhesus Macaques

Author:

Miller-Novak Leia K.1,Das Jishnu2ORCID,Musich Thomas A.1,Demberg Thorsten1,Weiner Joshua A.3,Venzon David J.4ORCID,Mohanram Venkatramanan1,Vargas-Inchaustegui Diego A.1,Tuero Iskra1,Ackerman Margaret E.3,Alter Galit2,Robert-Guroff Marjorie1

Affiliation:

1. Vaccine Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

2. Ragon Institute of MGH, MIT and Harvard University, Cambridge, Massachusetts, USA

3. Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA

4. Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Abstract

An HIV vaccine would thwart the spread of HIV infection and save millions of lives. Unfortunately, the immune responses conferring universal protection from HIV infection are poorly defined. The innate immune system, including the complement system, is an evolutionarily conserved, basic means of protection from infection. Complement can prevent infection by directly lysing incoming pathogens. We found that vaccination against SIV in rhesus macaques induces antibodies that are capable of directing complement lysis of SIV and SIV-infected cells in both sexes. We also found sex differences in vaccine-induced antibody species and their functions. Overall, our data suggest that sex affects vaccine-induced antibody characteristics and function and that males and females might require different immune responses to protect against HIV infection. This information could be used to generate highly effective HIV vaccines for both sexes in the future.

Funder

Intramural Research Program of the NIH, NCI

Gates Foundation

NIH R37

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference67 articles.

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