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The development of population immunity, through responses directed to highly immunogenic regions of this virus, has been a strong driving force in the emergence of progressively mutated variants. This review highlights how the strength of the existing global virology and immunology networks built for HIV vaccine research enabled rapid adaptation of techniques, assays, and skill sets, to expeditiously respond to the SARS\u2010CoV\u20102 pandemic. Allying real\u2010time genomic surveillance to immunological platforms enabled the characterization of immune responses elicited by infection with distinct variants, in sequential epidemic waves, as well as studies of vaccination and hybrid immunity (combination of infection\u2010 and vaccination\u2010induced immunity). These studies have shown that consecutive variants of concern have steadily diminished the ability of vaccines to prevent infection, but that increasing levels of hybrid immunity result in higher frequencies of cross\u2010reactive responses. Ultimately, this rapid pivot from HIV to SARS\u2010CoV\u20102 enabled a depth of understanding of the SARS\u2010CoV\u20102 antigenic vulnerabilities as population immunity expanded and diversified, providing key insights for future responses to the SARS\u2010CoV\u20102 pandemic.<\/jats:p>","DOI":"10.1111\/imr.13086","type":"journal-article","created":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T03:33:50Z","timestamp":1653276830000},"page":"61-75","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Leveraging South African <scp>HIV<\/scp> research to define <scp>SARS\u2010CoV<\/scp>\u20102 immunity triggered by sequential variants of concern"],"prefix":"10.1111","volume":"310","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6354-4003","authenticated-orcid":false,"given":"Jinal N.","family":"Bhiman","sequence":"first","affiliation":[{"name":"National Institute for Communicable Diseases of the National Health 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