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

• Published in: Vaccines (Basel) Vol. 11; no. 11; p. 1663
• Main Authors: Elizalde-Torrent, Aleix, Borgognone, Alessandra, Casadellà, Maria, Romero-Martin, Luis, Escribà, Tuixent, Parera, Mariona, Rosales-Salgado, Yaiza, Díaz-Pedroza, Jorge, Català-Moll, Francesc, Noguera-Julian, Marc, Brander, Christian, Paredes, Roger, Olvera, Alex
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2023
• Subjects: AIDS vaccines; Analysis; Animal euthanasia; Antibiotics; Antibodies; Antigens; Bacteria; Cell-mediated cytotoxicity; Composition; Dendritic cells; Deoxyribonucleic acid; Depletion; Digestive system; Digestive tract; DNA; Dosage and administration; Drinking water; HIV; Human immunodeficiency virus; IFNγ; IL-22; Immune response; Immune system; Immunization; Immunogenicity; Interleukin 22; Intestinal microflora; Intestine; Large intestine; Lymphocytes T; Males; Microbiota; Microbiota (Symbiotic organisms); Microorganisms; Pathogens; Serum levels; Severe acute respiratory syndrome coronavirus 2; Spleen; T-cell; vaccine; Vaccines; γ-Interferon; Spain
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines11111663

Despite the important role of gut microbiota in the maturation of the immune system, little is known about its impact on the development of T-cell responses to vaccination. Here, we immunized C57BL/6 mice with a prime-boost regimen using DNA plasmid, the Chimpanzee Adenovirus, and the modified Vaccinia Ankara virus expressing a candidate HIV T-cell immunogen and compared the T-cell responses between individuals with an intact or antibiotic-depleted microbiota. Overall, the depletion of the gut microbiota did not result in significant differences in the magnitude or breadth of the immunogen-specific IFNγ T-cell response after vaccination. However, we observed marked changes in the serum levels of four cytokines after vaccinating microbiota-depleted animals, particularly a significant reduction in IL-22 levels. Interestingly, the level of IL-22 in serum correlated with the abundance of Roseburia in the large intestine of mice in the mock and vaccinated groups with intact microbiota. This short-chain fatty acid (SCFA)-producing bacterium was significantly reduced in the vaccinated, microbiota-depleted group. Therefore, our results indicate that, although microbiota depletion reduces serum levels of IL-22, the powerful vaccine regime used could have overcome the impact of microbiota depletion on IFNγ-producing T-cell responses.