Harnessing Coordinated CD4⁺ and CD8⁺ T-Cell Immunity for Virus-Specific Adoptive Immunotherapy in Africa

Abstract

Virus-specific T-cell (VST) therapy has developed principally for persistent or reactivating viral infections in immunocompromised patients, with the strongest clinical experience involving cytomegalovirus, Epstein–Barr virus, human adenovirus, BK polyomavirus and human herpesvirus 6. Whether this approach can be extended to emerging and re-emerging viral infections remains less certain. Evidence that virus-specific CD4⁺ and CD8⁺ T cells contribute to natural or vaccine-induced protection provides a biological basis for therapeutic development but does not establish the efficacy of adoptively transferred VSTs. This distinction is particularly important for viruses of relevance to Africa, including Ebola virus, Lassa virus, Marburg virus, dengue virus, chikungunya virus, Rift Valley fever virus and mpox virus. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) provides clinical proof-of-concept that rapidly developed, partially HLA-matched or banked virus-reactive T-cell products can be administered against a newly emerging pathogen. Experimental adoptive transfer studies provide additional evidence for selected pathogens, including Ebola virus, whereas other emerging viruses remain supported mainly by human immunological, epitope or preclinical data. Translation to African populations will require definition of protective viral targets, population-relevant HLA restrictions, viral sequence conservation, manufacturing feasibility and clinical indications in which cellular therapy offers a clear advantage. This review examines the evidence required to move from antiviral T-cell immunity to therapeutic VST development and proposes a framework for evaluating emerging and re-emerging viral infections as future VST targets in Africa.