Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses

Irshad Ahmed Hajam, Chih-Ming Tsai, Cesia Gonzalez, Juan Raphael Caldera, María Lázaro Díez, Xin Du, April Aralar, Brian Lin, William Duong and George Y. Liu ()
Additional contact information
Irshad Ahmed Hajam: University of California San Diego
Chih-Ming Tsai: University of California San Diego
Cesia Gonzalez: University of California San Diego
Juan Raphael Caldera: University of California San Diego
María Lázaro Díez: University of California San Diego
Xin Du: University of California San Diego
April Aralar: University of California San Diego
Brian Lin: University of California San Diego
William Duong: University of California San Diego
George Y. Liu: University of California San Diego

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54644-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54644-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54644-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().