Rectal microbiome composition correlates with humoral immunity to HIV-1 in vaccinated rhesus macaques

Sonny R. Elizaldi, Anil Verma, Korey A. Walter, Matthew Rolston, Ashok R. Dinasarapu, Blythe P. Durbin-Johnson, Matthew Settles, Pamela A. Kozlowski, Reben Raeman, Smita S. Iyer

Research output: Contribution to journalArticlepeer-review

Abstract

The microbiome is an integral and dynamic component of the host and is emerging as a critical determinant of immune responses; however, its influence on vaccine immunogenicity is largely not well understood. Here, we examined the pivotal relationship between the mucosal microbiome and vaccine-induced immune responses by assessing longitudinal changes in vaginal and rectal microbiome profiles after intradermal immunization with a human immunodeficiency virus type 1 (HIV-1) DNA vaccine in adult rhesus macaques that received two prior DNA primes. We report that both vaginal and rectal microbiomes were dominated by Firmicutes but were composed of distinct genera, denoting microbiome specialization across mucosal tissues. Following immunization, the vaginal microbiome was resilient, except for a transient decrease in Streptococcus. In contrast, the rectal microbiome was far more responsive to vaccination, exhibiting an increase in the ratio of Firmicutes to Bacteroidetes. Within Bacteroidetes, multiple genera were significantly decreased, including Prevotella, Alloprevotella, Bacteroides, Acetobacteroides, Falsiporphyromonas, and Anaerocella. Decreased abundance of Prevotella correlated with induction of gut-homing α4β7+ effector CD4 T cells. Prevotella abundance also negatively correlated with rectal HIV-1 specific IgG levels. While rectal Lactobacillus was unaltered following DNA vaccination, baseline Lactobacillus abundance showed strong associations with higher rectal HIV-1 gp140 IgA induced following a protein boost. Similarly, the abundance of Clostridium in cluster IV was associated with higher rectal HIV-1 gp140 IgG responses. Collectively, these data reveal that the temporal stability of bacterial communities following DNA immunization is site dependent and highlight the importance of host-microbiome interactions in shaping HIV-1 vaccine responses. Our findings have significant implications for microbial manipulation as a strategy to enhance HIV vaccine-induced mucosal immunity.

Original languageEnglish (US)
Article numbere00824
JournalmSphere
Volume4
Issue number6
DOIs
StatePublished - Jan 1 2019

Keywords

  • Antibody response
  • DNA
  • HIV-1
  • Microbiome
  • Vaccine

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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