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

Autor: Leia K. Miller-Novak, Joshua A. Weiner, Venkatramanan Mohanram, Galit Alter, Marjorie Robert-Guroff, Jishnu Das, Thorsten Demberg, Margaret E. Ackerman, Iskra Tuero, Diego A. Vargas-Inchaustegui, David Venzon, Thomas Musich
Rok vydání: 2018
Předmět:
Cytotoxicity
Immunologic
Male
0301 basic medicine
animal diseases
viruses
Simian Acquired Immunodeficiency Syndrome
Antibodies
Viral
antibody-dependent complement-mediated lysis
medicine.disease_cause
0302 clinical medicine
Viral Envelope Proteins
sex bias
purl.org/pe-repo/ocde/ford#1.06.02 [https]
SIV vaccine
HIV vaccine
Vaccines
Synthetic
Membrane Glycoproteins
SAIDS Vaccines
virus diseases
Acquired immune system
Vaccination
Female
Simian Immunodeficiency Virus
Antibody
Signal Transduction
Immunology
Immunization
Secondary
Biology
Microbiology
03 medical and health sciences
Sex Factors
Immune system
Virology
Vaccines and Antiviral Agents
medicine
Animals
Innate immune system
Immune Sera
Gene Products
env
Complement System Proteins
Simian immunodeficiency virus
Antibodies
Neutralizing
Macaca mulatta
Complement system
030104 developmental biology
Gene Expression Regulation
Immunoglobulin M
Immunoglobulin G
Insect Science
biology.protein
Adenoviruses
Simian
antibody glycosylation
rhesus macaque
030215 immunology
Zdroj: Journal of Virology. 92
ISSN: 1098-5514
0022-538X
DOI: 10.1128/jvi.00721-18
Popis: An effective human immunodeficiency virus (HIV) vaccine has yet to be developed, and defining immune correlates of protection against HIV infection is of paramount importance to inform future vaccine design. The complement system is a component of innate immunity that can directly lyse pathogens and shape adaptive immunity. To determine if complement lysis of simian immunodeficiency virus (SIV) and/or SIV-infected cells represents a protective immune correlate against SIV infection, sera from previously vaccinated and challenged rhesus macaques were analyzed for the induction of antibody-dependent complement-mediated lysis (ADCML). Importantly, the vaccine regimen, consisting of a replication-competent adenovirus type 5 host-range mutant SIV recombinant prime followed by a monomeric gp120 or oligomeric gp140 boost, resulted in overall delayed SIV acquisition only in females. Here, sera from all vaccinated animals induced ADCML of SIV and SIV-infected cells efficiently, regardless of sex. A modest correlation of SIV lysis with a reduced infection rate in males but not females, together with a reduced peak viremia in all animals boosted with gp140, suggested a potential for influencing protective efficacy. Gag-specific IgG and gp120-specific IgG and IgM correlated with SIV lysis in females, while Env-specific IgM correlated with SIV-infected cell lysis in males, indicating sex differences in vaccine-induced antibody characteristics and function. In fact, gp120/gp140-specific antibody functional correlates between antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis, and ADCML as well as the gp120-specific IgG glycan profiles and the corresponding ADCML correlations varied depending on the sex of the vaccinees. Overall, these data suggest that sex influences vaccine-induced antibody function, which should be considered in the design of globally effective HIV vaccines in the future. IMPORTANCE 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.
Databáze: OpenAIRE
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