Neutralizing antibodies elicited by the Ad26.COV2.S COVID-19 vaccine show reduced activity against 501Y.V2 (B.1.351), despite protection against severe disease by this variant

Moore, Penny L; Moyo-Gwete, Thandeka; Hermanus, Tandile; Kgagudi, Prudence; Ayres, Frances; Makhado, Zanele; Sadoff, Jerald; Le Gars, Mathieu; van Roey, Griet; Crowther, Carol; Garrett, Nigel; Bekker, Linda-Gail; Morris, Lynn; Schuitemaker, Hanneke; Gray, Glenda

The emergence of SARS-CoV-2 variants, such as 501Y.V2, with immune evasion mutations in the spike has resulted in reduced efficacy of several COVID-19 vaccines. However, the efficacy of the Ad26.COV2.S vaccine, when tested in South Africa after the emergence of 501Y.V2, was not adversely impacted. We therefore assessed the binding and neutralization capacity of n=120 South African sera (from Day 29, post-vaccination) from the Janssen phase 3 study, Ensemble. Spike binding assays using both the Wuhan-1 D614G and 501Y.V2 Spikes showed high levels of cross-reactivity. In contrast, in a subset of 27 sera, we observed significantly reduced neutralization of 501Y.V2 compared to Wuhan-1 D614G, with 22/27 (82%) of sera showing no detectable neutralization of 501Y.V2 at Day 29. These data suggest that even low levels of neutralizing antibodies may contribute to protection from moderate/severe disease. In addition, Fc effector function and T cells may play an important role in protection by this vaccine against 501Y.V2.