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
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- 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
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- 12 months.
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
Statistical Analysis
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 4
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Richness Number of species
- unchanged
