Although mRNA SARS-CoV-2 vaccines are generally safe and effective, in certain immunocompromised individuals they can elicit poor immunogenic responses. Among these individuals, people living with HIV (PLWH) have poor immunogenicity to several oral and parenteral vaccines. As the gut microbiome is known to affect vaccine immunogenicity, we investigated whether baseline gut microbiota predicts immune responses to the BNT162b2 mRNA SARS-CoV-2 vaccine in healthy controls and PLWH after two doses of BNT162b2. Individuals with high spike IgG titers and high spike-specific CD4⁺ T-cell responses against SARS-CoV-2 showed low α-diversity in the gut. Here, we investigated and presented initial evidence that the gut microbial composition influences the response to BNT162b2 in PLWH. From our predictive models, Bifidobacterium and Faecalibacterium appeared to be microbial markers of individuals with higher spike IgG titers, while Cloacibacillus was associated with low spike IgG titers. We therefore propose that microbiome modulation could optimize immunogenicity of SARS-CoV-2 mRNA vaccines.

尽管 mRNA SARS-CoV-2 疫苗通常是安全有效的，但在某些免疫功能低下的个体中，它们可能会引起较差的免疫原性反应。在这些人中，艾滋病毒感染者（PLWH）对几种口服和肠胃外疫苗的免疫原性较差。由于已知肠道微生物群会影响疫苗的免疫原性，因此我们研究了基线肠道微生物群是否可以预测健康对照者和感染者在注射两剂 BNT162b2 后对 BNT162b2 mRNA SARS-CoV-2 疫苗的免疫反应。具有高刺突 IgG 滴度和针对 SARS-CoV-2 的高刺突特异性 CD4 ⁺ T 细胞反应的个体在肠道中表现出较低的 α 多样性。在这里，我们调查并提出了肠道微生物组成影响 PLWH 对 BNT162b2 反应的初步证据。根据我们的预测模型，双歧杆菌和粪杆菌似乎是具有较高峰值 IgG 滴度的个体的微生物标志物，而乳酸杆菌则与较低的峰值 IgG 滴度相关。因此，我们建议微生物组调节可以优化 SARS-CoV-2 mRNA 疫苗的免疫原性。