Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses

• Published in: Nature communications 2024-12, Vol.15 (1), p.10335-16, Article 10335
• Main Authors: Hajam, Irshad Ahmed, Tsai, Chih-Ming, Gonzalez, Cesia, Caldera, Juan Raphael, Lázaro Díez, María, Du, Xin, Aralar, April, Lin, Brian, Duong, William, Liu, George Y.
• Format: Article
• Language: English
• Subjects: 13/106; 631/250/1619/554/1898; 631/250/251/1574; 631/250/255/1318; 631/250/590; 64; 64/60; Adjuvants; Animals; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Female; Humanities and Social Sciences; Humans; Immune Evasion - immunology; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin 10; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukin-17 - immunology; Interleukin-17 - metabolism; Lymphocytes; Lymphocytes T; Mice; Mice, Inbred C57BL; multidisciplinary; Receptors, Interleukin-10 - immunology; Receptors, Interleukin-10 - metabolism; Science; Science (multidisciplinary); Staphylococcal Infections - immunology; Staphylococcal Infections - microbiology; Staphylococcal Infections - prevention & control; Staphylococcal Vaccines - immunology; Staphylococcus aureus - immunology; Vaccination; Vaccine development; Vaccines; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-54644-w

Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4 + T cell imprints, leading to the blunting of protective IsdB vaccine responses. Mechanistically, these SA-experienced CD4 + T cells express IL-10, which is further amplified by vaccination and impedes vaccine protection by binding with IL-10Rα on CD4 + T cell and inhibit IL-17A production. IL-10 also mediates cross-suppression of IsdB and sdrE multi-antigen vaccine. By contrast, the inefficiency of SA IsdB, IsdA and MntC vaccines can be overcome by co-treatment with adjuvants that promote IL-17A and IFN-γ responses. We thus propose that IL-10 secreting, SA-experienced CD4 + T cell imprints represent a staphylococcal immune escaping mechanism that needs to be taken into consideration for future vaccine development. Mechanisms of inefficient vaccine protection against pathobionts such as S. aureus (SA) are still unclear. Here the authors show that prior SA exposure induces non-protective CD4 + T cells, which impair IsdB vaccine protection by IL-10 secretion and IL-17A suppression, whereas IL-17A promoting adjuvant CAF01 overcomes this dilemma.