mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern

• Published in: Immunity (Cambridge, Mass.) Mass.), 2022-02, Vol.55 (2), p.355-365.e4
• Main Authors: Kaplonek, Paulina, Fischinger, Stephanie, Cizmeci, Deniz, Bartsch, Yannic C., Kang, Jaewon, Burke, John S., Shin, Sally A., Dayal, Diana, Martin, Patrick, Mann, Colin, Amanat, Fatima, Julg, Boris, Nilles, Eric J., Musk, Elon R., Menon, Anil S., Krammer, Florian, Saphire, Erica Ollman, Andrea Carfi, Alter, Galit
• Format: Article
• Language: English
• Subjects: 2019-nCoV Vaccine mRNA-1273 - administration & dosage; 2019-nCoV Vaccine mRNA-1273 - immunology; Adult; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; COVID-19; COVID-19 - metabolism; COVID-19 - prevention & control; Cross Reactions - immunology; Fc effector function; Female; Host-Pathogen Interactions; Humans; Male; Middle Aged; mRNA-1273 vaccination; Neutralization Tests; Protein Binding; Receptors, Fc - metabolism; SARS-CoV-2; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - immunology; Vaccination; vaccines; variants of concern; Young Adult
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2022.01.001

SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization. •mRNA-1273 vaccine induces spike antibodies that are able to leverage FcR binding across VOCs•Convalescent spike antibodies interact with VOCs but exhibit compromised FcR binding•VOCs differentially affect Fc effector functions in natural infection and vaccination•mRNA-1273-induced antibodies might confer protection independent of neutralization SARS-CoV-2 mRNA vaccines provide cross-variant protection against COVID-19. Whether this is mediated strictly via neutralization or is linked to effector functions that may limit, rather than block, transmission remains unknown. Kaplonek et al. show that mRNA-1273-vaccination-induced antibodies preserve Fc effector responses across variants of concern, whereas antibodies induced following natural infection show compromised interactions with Fc-receptors.