Targeting the gut microbiota to optimize vaccine efficacy?
by Dr Genelle Healey
About this article
Since the COVID-19 pandemic started, the need for a robust and long-lasting immunity induced by vaccines has never been more apparent.20 However, vaccine- induced immune responses are highly variable between individuals and many factors have been suggested that may alter vaccine immunogenicity and efficacy (Fig 8).21Therefore, gaining a better understanding of the factors driving variations in vaccine efficacy is critically important.
One factor known to control vaccine efficacy is the gut microbiota.21 Interestingly, certain gut microbiota profiles (i.e. higher abundance of Actinobacteria, Clostridium cluster XI and Proteobacteria) are associated with greater vaccine responses against other viral infections such as HIV and rotavirus.22-26 Additionally, a recent study reported that antibiotic-induced intestinal microbiota dysbiosis led to impaired vaccine responses against influenza, such as a reduced antibody-based neutralization of the virus, as well as lower concentrations of antibodies produced in responses to vaccination.27 This and other similar studies provide evidence of the important role that the gut microbiota plays in vaccine efficacy.23,28
FIGURE 8: Factors suggested to alter vaccine immunogenicity and/or efficacy, including intrinsic host factors, behavioural, environmental, nutritional and perinatal factors.
Most of these factors have also been shown to influence the composition of the gut microbiota and baseline immunity. Vaccine immunogenicity is also dependent on vaccine intrinsic factors.
Adapted for Lynn DJ et al, 202120
To date no studies have investigated what impact the gut microbiota may have on SARS-CoV-2 vaccine efficacy, but it seems likely that individuals with gut microbiota dysbiosis may be at increased risk of developing relatively poor vaccine responses. Thus, future research which examines whether specific gut microbiota signatures affect SARS-CoV-2 vaccine efficacy will be critically important.
20 Lynn DJ, Benson SC, Lynn MA, Pulendran B. Modulation of immune responses to vaccination by the microbiota: implications and potential mechanisms. Nat Rev Immunol. 2021 May 17:1–14.
21 de Jong SE, Olin A, Pulendran B. The Impact of the Microbiome on Immunity to Vaccination in Humans. Cell Host Microbe. 2020 Aug 12;28(2):169-179.
22 Harris VC, Armah G, Fuentes S, et al. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana. J Infect Dis. 2017 Jan 1;215(1):34-41.
23 Uchiyama R, Chassaing B, Zhang B, et al. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. J Infect Dis. 2014 Jul 15;210(2):171-82.
24 Huda MN, Lewis Z, Kalanetra KM, et al. Stool microbiota and vaccine responses of infants. Pediatrics. 2014 Aug;134(2):e362-72.
25 Cram JA, Fiore-Gartland AJ, Srinivasan S, et al. Human gut microbiota is associated with HIV-reactive immunoglobulin at baseline and following HIV vaccination. PLoS One. 2019 Dec 23;14(12):e0225622.
26 Harris V, Ali A, Fuentes S, et al. Rotavirus vaccine response correlates with the infant gut microbiota composition in Pakistan. Gut Microbes. 2018 Mar 4;9(2):93-101.
27 Hagan T, Cortese M, Rouphael N, et al. Antibiotics-Driven Gut Microbiome Perturbation Alters Immunity to Vaccines in Humans. Cell. 2019 Sep 5;178(6):1313-1328.e13.
28 Harris VC, Haak BW, Handley SA, et al. Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial. Cell Host Microbe. 2018 Aug 8;24(2):197-207.e4.