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Eight participants had detectable virus-specific T-cell responses, including a PWH who was not on antiretroviral therapy and a PWH on immunosuppressive therapy. These 2 participants had robust polyfunctional CD4+ T-cell responses to peptides from the 121L vaccinia virus (VACV) protein. T-cells from 4 of 5 HLA-A2\u2013positive participants targeted at least 1 previously described HLA-A2\u2013restricted VACV epitope, including an epitope targeted in 2 participants. 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