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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

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dc.contributor.author Miller-Novak, Leia K.
dc.contributor.author Das, Jishnu
dc.contributor.author Musich, Thomas A.
dc.contributor.author Demberg, Thorsten
dc.contributor.author Weiner, Joshua A.
dc.contributor.author Venzon, David J.
dc.contributor.author Mohanram, Venkatramanan
dc.contributor.author Vargas-Inchaustegui, Diego A.
dc.contributor.author Tuero Ochoa, Iskra
dc.contributor.author Ackerman, Margaret E.
dc.contributor.author Alter, Galit
dc.contributor.author Robert-Guroff, Marjorie
dc.date.accessioned 2018-11-30T23:41:31Z
dc.date.available 2018-11-30T23:41:31Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/20.500.12866/4217
dc.description.abstract 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. en_US
dc.language.iso eng
dc.publisher American Society for Microbiology
dc.relation.ispartofseries Journal of Virology
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject rhesus macaque en_US
dc.subject SIV vaccine en_US
dc.subject antibody glycosylation en_US
dc.subject antibody-dependent complement-mediated lysis en_US
dc.subject sex bias en_US
dc.title 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 en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.1128/JVI.00721-18
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#1.06.02
dc.relation.issn 1098-5514


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