tetano
Editor, Senior Moderator
Cell Stem Cell
. 2025 Feb 15:S1934-5909(25)00014-1.
doi: 10.1016/j.stem.2025.01.014. Online ahead of print. Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines
Zachary W Wagoner[SUP] 1 [/SUP], Timothy B Yates[SUP] 1 [/SUP], Jenny E Hernandez-Davies[SUP] 1 [/SUP], Suhas Sureshchandra[SUP] 1 [/SUP], Erika M Joloya[SUP] 1 [/SUP], Aarti Jain[SUP] 2 [/SUP], Rafael de Assis[SUP] 2 [/SUP], Jenna M Kastenschmidt[SUP] 1 [/SUP], Andrew M Sorn[SUP] 1 [/SUP], Mahina Tabassum Mitul[SUP] 1 [/SUP], Ian Tamburini[SUP] 3 [/SUP], Gurpreet Ahuja[SUP] 4 [/SUP], Qiu Zhong[SUP] 4 [/SUP], Douglas Trask[SUP] 5 [/SUP], Marcus Seldin[SUP] 3 [/SUP], D Huw Davies[SUP] 1 [/SUP], Lisa E Wagar[SUP] 6 [/SUP]
Affiliations
Vaccines are an essential tool to significantly reduce pathogen-related morbidity and mortality. However, our ability to rationally design vaccines and identify correlates of protection remains limited. Here, we employed an immune organoid approach to capture human adaptive immune response diversity to influenza vaccines and systematically identify host and antigen features linked to vaccine response variability. Our investigation identified established and unique immune signatures correlated with neutralizing antibody responses across seven different influenza vaccines and antigens. Unexpectedly, heightened ex vivo tissue frequencies of T helper (Th)1 cells emerged as both a predictor and a correlate of neutralizing antibody responses to inactivated influenza vaccines (IIVs). Secondary analysis of human public data confirmed that elevated Th1 signatures are associated with antibody responses following in vivo vaccination. These findings demonstrate the utility of human in vitro models for identifying in vivo correlates of protection and establish a role for Th1 functions in influenza vaccination.
Keywords: adaptive immunity; humoral immunity; immune organoids; lymphoid tissues; predictive modeling; systems immunology; vaccines.
. 2025 Feb 15:S1934-5909(25)00014-1.
doi: 10.1016/j.stem.2025.01.014. Online ahead of print. Systems immunology analysis of human immune organoids identifies host-specific correlates of protection to different influenza vaccines
Zachary W Wagoner[SUP] 1 [/SUP], Timothy B Yates[SUP] 1 [/SUP], Jenny E Hernandez-Davies[SUP] 1 [/SUP], Suhas Sureshchandra[SUP] 1 [/SUP], Erika M Joloya[SUP] 1 [/SUP], Aarti Jain[SUP] 2 [/SUP], Rafael de Assis[SUP] 2 [/SUP], Jenna M Kastenschmidt[SUP] 1 [/SUP], Andrew M Sorn[SUP] 1 [/SUP], Mahina Tabassum Mitul[SUP] 1 [/SUP], Ian Tamburini[SUP] 3 [/SUP], Gurpreet Ahuja[SUP] 4 [/SUP], Qiu Zhong[SUP] 4 [/SUP], Douglas Trask[SUP] 5 [/SUP], Marcus Seldin[SUP] 3 [/SUP], D Huw Davies[SUP] 1 [/SUP], Lisa E Wagar[SUP] 6 [/SUP]
Affiliations
- PMID: 39986275
- DOI: 10.1016/j.stem.2025.01.014
Vaccines are an essential tool to significantly reduce pathogen-related morbidity and mortality. However, our ability to rationally design vaccines and identify correlates of protection remains limited. Here, we employed an immune organoid approach to capture human adaptive immune response diversity to influenza vaccines and systematically identify host and antigen features linked to vaccine response variability. Our investigation identified established and unique immune signatures correlated with neutralizing antibody responses across seven different influenza vaccines and antigens. Unexpectedly, heightened ex vivo tissue frequencies of T helper (Th)1 cells emerged as both a predictor and a correlate of neutralizing antibody responses to inactivated influenza vaccines (IIVs). Secondary analysis of human public data confirmed that elevated Th1 signatures are associated with antibody responses following in vivo vaccination. These findings demonstrate the utility of human in vitro models for identifying in vivo correlates of protection and establish a role for Th1 functions in influenza vaccination.
Keywords: adaptive immunity; humoral immunity; immune organoids; lymphoid tissues; predictive modeling; systems immunology; vaccines.