After vaccination with RTS,S/AS01E, an increasing frequency of TNFα producing, CS-specific CD4+ cells detected using ICS was associated with a reduced risk of clinical malaria (HR = 0.64 for each 10 fold increase in the frequency of CD4+ TNFα+ T cells, 95%CI 0.49–0.86, p = 0.002). The gene discussed is CD4; the disease is malaria.