CD4 and infection: • CD4+ T cells are generated by both infection and vaccination, though their functional capacities differ. Ideally, vaccines would elicit more robust IFN-γ-producing CD4+ T cell responses.• Whether CD4+ T cells are directly involved in protection is not clear, but would be valuable to understand from the perspective of vaccine development.• While CD4+ responses to TBEV structural proteins are well-documented in response to vaccination and infection, additional information on responses to NS proteins during infection would be useful to identify additional vaccine targets.