Human gut microbiota is associated with HIV-reactive immunoglobulin at baseline and following HIV vaccination

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Reviewed Marked as Reviewed by Lwaldron on 2023-10-15
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DOI Digital object identifier for electronic documents.
Cram JA, Fiore-Gartland AJ, Srinivasan S, Karuna S, Pantaleo G, Tomaras GD, Fredricks DN, Kublin JG
PloS one
Antibodies that recognize commensal microbial antigens may be cross reactive with a part of the human immunodeficiency virus (HIV) envelope glycoprotein gp41. To improve understanding of the role of the microbiota in modulating the immune response to HIV vaccines, we studied the associations of the gut microbiota composition of participants in the HIV Vaccine Trials Network 096 clinical trial with their HIV-specific immune responses in response to vaccination with a DNA-prime, pox virus boost strategy designed to recapitulate the only efficacious HIV-vaccine trial (RV144). We observed that both levels of IgG antibodies to gp41 at baseline and post-vaccination levels of IgG antibodies to the Con.6.gp120.B, ZM96.gp140 and gp70 B.CaseA V1-V2 antigens were associated with three co-occurring clusters of family level microbial taxa. One cluster contained several families positively associated with gp41-specific IgG and negatively associated with vaccine-matched gp120, gp140 and V1-V2-specific IgG responses. A second cluster contained families that negatively associated with gp41 and positively associated with gp120, gp140 and V1-V2-specific IgG responses. A third cluster contained microbial groups that did not correlate with any immune responses. Baseline and post-vaccination levels of gp41 IgG were not significantly correlated, suggesting that factors beyond the microbiome that contribute to immune response heterogeneity. Sequence variant richness was positively associated with gp41, p24, pg140 and V1-V2 specific IgG responses, gp41 and p24 IgA responses, and CD4+ T cell responses to HIV-1 proteins. Our findings provide preliminary evidence that the gut microbiota may be an important predictor of vaccine response.

Experiment 1

Reviewed Marked as Reviewed by Lwaldron on 2023-10-15

Curated date: 2022/01/11

Curator: Joyessa

Revision editor(s): Joyessa, LGeistlinger, Chinelsy


Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Mucosa of rectum Mucosa of organ of rectum,Mucous membrane of rectum,Organ mucosa of rectum,Rectal mucosa,Rectal mucous membrane,Rectum mucosa,Rectum mucosa of organ,Rectum mucous membrane,Rectum organ mucosa,Mucosa of rectum,mucosa of rectum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to vaccine Response to vaccine,response to vaccine
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
Vaccinated participants
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants who were vaccinated
Group 0 sample size Number of subjects in the control (unexposed) group
Group 1 sample size Number of subjects in the case (exposed) group

Lab analysis

Sequencing type
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Statistical Analysis

Statistical test
Logistic Regression
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
Richness Number of species

Signature 1

Reviewed Marked as Reviewed by Chinelsy on 2023-11-8

Curated date: 2023/10/15

Curator: Chinelsy

Revision editor(s): Chinelsy

Source: Fig 4.

Description: The microbiota vary between participants and can be described by weighted UniFrac axis 1 (MDS1). Variations along this axis are evident at the family level within certain classes and orders.

Abundance in Group 1: increased abundance in Vaccinated participants

NCBI Quality ControlLinks

Revision editor(s): Chinelsy