Correlation of the Gut Microbiota and Antitumor Immune Responses Induced by a Human Papillomavirus Therapeutic Vaccine

Abstract

Human papillomavirus (HPV) is the most common sexually transmitted pathogen worldwide and the major risk factor for cervical cancer. According to our previous study, antitumor immune responses induced by a therapeutic vaccine based on HPV E7 peptide are highly variable among individuals. Many studies have demonstrated that the discrepancy in the gut microbiota is an important factor in the development and regulation of the immune system. Therefore, we performed a systematic comparative analysis of gut microbiota in two groups of mice with significant differences in antitumor effects induced by the vaccine, as well as the correlation between immune cells and gut microbiota. We divided the mice into group A, in which the tumor continued growing, and group B, in which the tumor volume was significantly reduced. In group B mice, the vaccination induced a stronger antitumor activity with significantly enhanced IFN-γ-producing CD4+ and CD8+ T lymphocytes, as well as decreased immunosuppressive cells. A detailed gut microbiota analysis revealed a positive Spearman correlation between the percentage of CD8+ T cells and the relative abundance of Corynebacteriales, Parabacteroides, and Bacteroides_sp. Furthermore, the percentage of CD4+ and CD8+ T cells negatively correlated with the abundance of Proteobacteria and Bilophila. By contrast, the abundance of Proteobacteria, Desulfovibrio, and Bilophila positively correlated with the percentage of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and type 2-polarized tumor-associated macrophages (M2-TAMs). Overall, the composition of gut microbiota is related to vaccineinduced antitumor effects, and there is a correlation between some gut bacteria and vaccine-induced immune responses.

Vaccination with an HIV T-Cell Immunogen (HTI) Using DNA Primes Followed by a ChAdOx1-MVA Boost Is Immunogenic in Gut Microbiota-Depleted Mice despite Low IL-22 Serum Levels

“…In line with this, several reports have described the influence of the gut microbiome on the immunogenicity of SARS-CoV-2, Rotavirus, Human Papillomavirus, Polio, Tetanus, Pneumococcus and Vibrio cholera vaccines [40][41][42][43][44][45][46][47][48]. Moreover, microbiota dysbiosis caused by antibiotic use has been shown to have detrimental effects on vaccine response [2] and to reduce antibody levels and CD8+ T-cell responses to influenza vaccination [35,49].…”