In immunodeficient macaques with CD4+ T cell counts < 300 cells/mm3, smallpox vaccination is ineffective against lethal MPXV infections.[179] CD4+ T cells recognize HLA‐DR1‐restricted epitopes on the conserved VACV proteins A24R and D1R, which can be exploited to analyze CD4+ T cell responses to existing or next‐generation smallpox vaccines.[180] Following infection with MPXV, smallpox vaccine‐protective E3L‐specific T‐cells protect patients from viral attack by killing infected cells and peptide‐loaded target cells.[181] D8 is a protective antigen against intracellular maturation. The gene discussed is CD4; the disease is infection.