Heterologous infections
Define the role of heterologous infections (e.g., sequential infection with different influenza A virus strains) on the establishment and maintenance of CD4 and CD8 T cells.
Progress Highlights
Sircy 2024 used a heterologous infection or immunization priming strategy to seed an antigen-specific memory CD4 T-cell pool prior to influenza infection in mice to evaluate the effect of recalled memory T follicular helper cells in increased help to influenza-specific primary B cells and enhanced generation of neutralizing antibodies. Results showed that heterologous priming induced an increase in both CD4 T cells and B cells early following influenza infection, suggesting successful target enhancement of the germinal center, but did not result in an increase in influenza-specific antiviral antibodies.
Bull 2023 determined the early cytokine impact of HA mismatch during infection of mice vaccinated with a T-cell activating next-generation influenza vaccine, showing the negative effect of exuberant cytokine production and subsequent mild morbidity in sublethal seasonal influenza infection, outcomes that were outweighed by the essential benefit of survival against highly lethal AIVs and higher doses of seasonal influenza viruses.
Currenti 2023 examined the TCR repertoire and transcriptional profile of vaccine-induced circulating T follicular helper (cTfh) cells in individuals who received sequential seasonal influenza vaccines and identified the expansion and transcriptomic profile of vaccine-induced cTfh cells important for B-cell help.