Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Keeton, Roanne; Richardson, Simone I.; Moyo-Gwete, Thandeka; Hermanus, Tandile; Tincho, Marius B.; Benede, Ntombi; Manamela, Nelia P.; Baguma, Richard; Makhado, Zanele; Ngomti, Amkele; Motlou, Thopisang; Mennen, Mathilda; Chinhoyi, Lionel; Skelem, Sango; Maboreke, Hazel; Doolabh, Deelan; Iranzadeh, Arash; Otter, Ashley D.; Brooks, Tim; Noursadeghi, Mahdad; Moon, James; Grifoni, Alba; Weiskopf, Daniela; Sette, Alessandro; Blackburn, Jonathan; Hsiao, Nei-Yuan; Williamson, Carolyn; Riou, Catherine; Goga, Ameena; Garrett, Nigel; Bekker, Linda-Gail; Gray, Glenda; Ntusi, Ntobeko A.B.; Moore, Penny L.; Burgers, Wendy A.

The Johnson and Johnson Ad26.COV2.S single dose vaccine represents an attractive option for COVID-19 vaccination in resource limited countries. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naïve with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike binding antibodies, antibody-dependent cellular cytotoxicity and neutralizing antibodies against D614G, Beta and Delta, however neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination following infection may result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.