Human T-cell responses to vaccinia virus envelope proteins

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Current smallpox vaccines use live vaccinia virus (VACV), posing risks.
• Recombinant subunit vaccines offer a safer alternative.
• VACV envelope proteins A27L, L1R, B5R, and A33R are known to induce protective antibodies.

Purpose of the Study:

• To investigate T-cell responses to VACV envelope proteins for developing molecular vaccines.
• To assess the role of T-cell immunity alongside antibody responses in VACV vaccination.

Main Methods:

• Peripheral blood mononuclear cells (PBMC) from VACV vaccinees were analyzed.
• Assays included gamma interferon enzyme-linked immunospot and cytokine flow cytometry.
• PBMC were stimulated with VACV-infected dendritic cells or mRNA-electroporated dendritic cells expressing VACV proteins.

Main Results:

• All four VACV envelope proteins (A27, B5, L1, A33) were recognized by T-cells from individuals vaccinated up to 20 years prior.
• Both CD4(+) and CD8(+) T-cell responses were detected for each protein.
• High frequencies of T-cell precursors specific to B5 and A27 were observed in a recent vaccinee.

Conclusions:

• The four VACV envelope proteins are immunogenic and elicit both antibody and T-cell responses.
• These proteins are potential candidates for inclusion in subunit or molecular smallpox vaccines.
• T-cell responses to these proteins contribute to protective immunity against VACV.