Adenovirus-specific human T cells are pervasive, polyfunctional, and cross-reactive

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Pre-existing immunity to adenovirus (Ad) can reduce the effectiveness of Ad-based vaccines.
• Understanding Ad-specific T cell responses is crucial for improving vaccine design.

Purpose of the Study:

• To characterize the prevalence, magnitude, functionality, and phenotype of Ad-specific human T cells ex vivo.
• To assess the impact of Ad-specific T cells on Ad vector-based vaccine efficacy.

Main Methods:

• Developed a whole Ad vector stimulation assay for polychromatic flow cytometry.
• Analyzed Ad-specific CD4(+) and CD8(+) T cell responses in human subjects.
• Investigated cross-serotype reactivity against different Ad serotypes.

Main Results:

• Ad-specific CD4(+) and CD8(+) T cells were detected in all subjects tested and capable of proliferation.
• Ad5-specific CD4(+) T cells were largely monofunctional, while CD8(+) T cells were more polyfunctional.
• Cross-serotype reactivity against AdC6 and AdC7 was observed, attributed to conserved hexon regions.

Conclusions:

• Ad-specific T cells are prevalent and exhibit cross-reactivity, potentially impacting Ad vector-based vaccine efficacy.
• The effector functions of these T cells may lead to the elimination of Ad vector-infected cells.
• Findings highlight the need to consider pre-existing Ad immunity in vaccine development.