Two overlapping subdominant epitopes identified by DNA immunization induce protective CD8(+) T-cell populations with...

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Subdominant CD8(+) T-cell responses are vital for controlling viral infections and vaccine efficacy.
• Identifying these responses has been challenging using conventional methods.

Purpose of the Study:

• To investigate the utility of DNA immunization for identifying subdominant T-cell epitopes.
• To compare the protective immunity and memory profiles induced by dominant and subdominant epitopes.

Main Methods:

• Utilized a lymphocytic choriomeningitis virus (LCMV) mouse model.
• Employed DNA immunization to identify subdominant epitopes within the viral nucleoprotein.
• Compared T-cell kinetics, cytokine responsiveness, and lytic activity between dominant and subdominant responses post-vaccination and infection.

Main Results:

• DNA immunization reliably identified two overlapping subdominant CD8(+) T-cell epitopes presented by L(d) and K(d).
• Subdominant epitopes conferred immunity as effective as the dominant epitope, which typically elicits >90% of the antiviral CD8(+) T-cell response.
• Subdominant vaccination resulted in a more diverse memory T-cell pool compared to dominant vaccination after viral clearance.
• Subdominant CD8(+) T cells acquired cytokine responsiveness before lytic activity during acute infection, with lytic activity declining faster than cytokine responsiveness in both populations.

Conclusions:

• DNA immunization is a powerful tool for discovering functionally relevant subdominant CD8(+) T-cell epitopes.
• Subdominant epitopes can induce potent and broad protective immunity, comparable to dominant epitopes.
• Vaccine design can be tailored to selectively induce CD8(+) T cells with specific functional attributes, enhancing tailored immune responses.