Virus-driven Inflammation Is Associated With the Development of bNAbs in Spontaneous Controllers of HIV

Background. Understanding the mechanism(s) by which broadly neutralizing antibodies (bNAbs) emerge naturally following infection is crucial for the development of a protective vaccine against human immunodeficiency virus (HIV). Although previous studies have implicated high viremia and associated im...

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Bibliographic Details
Published in:Clinical infectious diseases 2017-04, Vol.64 (8), p.1098-1104
Main Authors: Dugast, Anne-Sophie, Arnold, Kelly, Lofano, Giuseppe, Moore, Sarah, Hoffner, Michelle, Simek, Melissa, Poignard, Pascal, Seaman, Michael, Suscovich, Todd J., Pereyra, Florencia, Walker, Bruce D., Lauffenburger, Doug, Kwon, Douglas S., Keele, Brandon F., Alter, Galit
Format: Article
Language:English
Subjects:
Antibodies, Neutralizing
Antibodies, Neutralizing - blood
Antigens
Antiretroviral drugs
ARTICLES AND COMMENTARIES
Biochemistry, Molecular Biology
Cytokines
Cytokines - blood
Editor's Choice
HIV
HIV - immunology
HIV Antibodies
HIV Antibodies - blood
HIV Infections
HIV Infections - immunology
HIV Infections - pathology
Human immunodeficiency virus
Humans
Inflammation
Inflammation - pathology
Intestinal Mucosa
Intestinal Mucosa - virology
Lentivirus
Life Sciences
Major
Plasma
Retroviridae
Ribonucleic acid
RNA
RNA, Viral
RNA, Viral - blood
Structural Biology
Viral Load
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Summary:Background. Understanding the mechanism(s) by which broadly neutralizing antibodies (bNAbs) emerge naturally following infection is crucial for the development of a protective vaccine against human immunodeficiency virus (HIV). Although previous studies have implicated high viremia and associated immune activation as potential drivers for the development of bNAbs, here we sought to unlink the effect of these 2 parameters by evaluating the key inflammatory predictors of bNAb development in HIV-infected individuals who spontaneously control HIV in the absence of antiretroviral therapy ("controllers"). Methods. The breadth of antibody-mediated neutralization against 11 tier 2 or 3 viruses was assessed in 163 clade B spontaneous controllers of HIV. Plasma levels of 17 cytokines were screened in the same set of subjects. The relationship of the inflammatory signature was assessed in the context of viral blips or viral RNA levels in peripheral blood or gastrointestinal biopsies from aviremic controllers (
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/cix057