CD4 and infection: Interestingly, while unexposed individuals exhibited an increase in the frequencies of Wuhan, Gamma, and Mu S-specific CD4+ T cells upon vaccination (Figure 5B), this was not the case for individuals with a history of natural infection, since they exhibited high frequencies of Wuhan, Gamma, and Mu S-specific CD4+ T cells during the pre-vaccination period, and only had a modest increase in the frequency of Wuhan S-specific CD4+ T cells upon vaccination (Figure 5C).