September 22, 2020

Rational vaccine design

Understanding immunity generated by smallpox vaccine may hold lessons for COVID-19 vaccine development.

Vaccination with vaccinia virus (VACV) — a member of the poxvirus family — elicits immunity to other family members: smallpox, monkeypox and mousepox. It is generally assumed that this protective “heterotypic immunity” happens because the VACV-derived epitopes (parts of proteins) recognized by CD8+ T cells are similar to epitopes generated by infection with other poxviruses. 

Sebastian JoycePhD, and colleagues have now comprehensively tested this assumption using a large panel of VACV-derived peptides in a mousepox (ECTV) infection model. They found that most dominant epitopes recognized by ECTV- and VACV-reactive CD8+ T cells overlapped significantly. However, some epitopes were only recognized by ECTV-, but not VACV-reactive CD8+ T cells, and vice versa. 

The findings in Scientific Reports provide a mechanistic basis for heterotypic immunity arising from VACV vaccination and are essential for the rational design of subunit (protein)-based vaccine that protects against smallpox and monkeypox disease. Heterotypic immunity may have implications for T cell-targeted vaccine design against COVID-19 as well.

This research was supported by a VA Merit Award and by grants from the National Institutes of Health (AI040079, AI121626, CA068485, DK058404).