The effect of cilgavimab and neutralisation by vaccine-induced antibodies in emerging SARS-CoV-2 BA.4 and BA.5 sublineages

• Published in: The Lancet infectious diseases 2022-12, Vol.22 (12), p.1665-1666
• Main Authors: Arora, Prerna, Zhang, Lu, Nehlmeier, Inga, Kempf, Amy, Cossmann, Anne, Dopfer-Jablonka, Alexandra, Schulz, Sebastian R, Jäck, Hans-Martin, Behrens, Georg M N, Pöhlmann, Stefan, Hoffmann, Markus
• Format: Article
• Language: English
• Subjects: Advisors; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; Coronaviruses; Correspondence; COVID-19 - prevention & control; COVID-19 vaccines; Funding; Humans; Immune response; Immunization; Infections; Infectious diseases; Infectivity; mRNA; Mutation; Protein S; Proteins; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Vaccines; Viral diseases
• ISSN: 1473-3099; 1474-4457
• DOI: 10.1016/S1473-3099(22)00693-4

Since the first detection of the SARS-CoV-2 omicron variant (B.1.1.529 and sublineages) in November 2021 in South Africa, Botswana, and Hong Kong, several omicron sublineages have evolved. Some of these sublineages, including BA.2.75, BA.4, and BA.5, have shown augmented resistance against antibody-mediated neutralisation.1–3 Thus, these sublineages outcompete earlier Omicron sublineages in populations with pre-existing immune responses due to either infection, or vaccination, or both.4 In the past months viruses that belong to different BA.4 and BA.5 sublineages and which have mutations at residue R346 (R346T, R346S, or R346S) within the receptor-binding domain of the viral spike S-protein have been detected with increased frequency5 (appendix p 1) This increased frequency has been detected for sublineages BA.4.6 (R346T or N658S), BA.5.9 (R346I), and BF.7 (R346T). Since the protein S mediates viral entry into cells and constitutes the key target for neutralising antibodies, we investigated whether mutation at R346T, R346S, or R346S might increase infectivity, or neutralisation resistance, or both. [...]we assessed neutralisation of S protein-driven cell entry by antibodies elicited upon triple vaccination with different combinations of the BNT162b2 mRNA and AZD1222 adenovirus-based vaccines, and early omicron wave (ie, February–May, 2022, in Germany) breakthrough infection in triple vaccinated individuals (appendix, table).