Heterologous immunization with inactivated vaccine followed by mRNA-booster elicits strong immunity against SARS-CoV-2 Omicron variant

Fanglei Zuo, Hassan Abolhassani, Likun Du, Antonio Piralla, Federico Bertoglio, Leire Campos-Mata, Hui Wan, Maren Schubert, Irene Cassaniti, Yating Wang, Josè Camilla Sammartino, Rui Sun, Stelios Vlachiotis, Federica Bergami, Makiko Kumagai-Braesch, Juni Andréll, Zhaoxia Zhang, Yintong Xue, Esther Veronika Wenzel, Luigi Calzolai, Luca Varani, Nima Rezaei, Zahra Chavoshzadeh, Fausto Baldanti, Michael Hust, Lennart Hammarström, Harold Marcotte and Qiang Pan-Hammarström ()
Additional contact information
Fanglei Zuo: Karolinska Institutet
Hassan Abolhassani: Karolinska Institutet
Likun Du: Karolinska Institutet
Antonio Piralla: Fondazione IRCCS Policlinico San Matteo
Federico Bertoglio: Technische Universität Braunschweig
Leire Campos-Mata: Karolinska Institutet
Hui Wan: Karolinska Institutet
Maren Schubert: Technische Universität Braunschweig
Irene Cassaniti: Fondazione IRCCS Policlinico San Matteo
Yating Wang: Karolinska Institutet
Josè Camilla Sammartino: Fondazione IRCCS Policlinico San Matteo
Rui Sun: Karolinska Institutet
Stelios Vlachiotis: Karolinska Institutet
Federica Bergami: Fondazione IRCCS Policlinico San Matteo
Makiko Kumagai-Braesch: CLINTEC, Karolinska Institutet at Karolinska University Hospital
Juni Andréll: Stockholm University
Zhaoxia Zhang: Karolinska University Hospital Huddinge
Yintong Xue: Peking University Health Science Center
Esther Veronika Wenzel: Technische Universität Braunschweig
Luigi Calzolai: European Commission, Joint Research Centre
Luca Varani: Università della Svizzera italiana (USI)
Nima Rezaei: Tehran University of Medical Sciences
Zahra Chavoshzadeh: Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences
Fausto Baldanti: Fondazione IRCCS Policlinico San Matteo
Michael Hust: Technische Universität Braunschweig
Lennart Hammarström: Karolinska Institutet
Harold Marcotte: Karolinska Institutet
Qiang Pan-Hammarström: Karolinska Institutet

Nature Communications, 2022, vol. 13, issue 1, 1-8

Abstract: Abstract The recent emergence of the Omicron variant has raised concerns on vaccine efficacy and the urgent need to study more efficient vaccination strategies. Here we observed that an mRNA vaccine booster in individuals vaccinated with two doses of inactivated vaccine significantly increased the plasma level of specific antibodies that bind to the receptor-binding domain (RBD) or the spike (S) ectodomain (S1 + S2) of both the G614 and the Omicron variants, compared to two doses of homologous inactivated vaccine. The level of RBD- and S-specific IgG antibodies and virus neutralization titers against variants of concern in the heterologous vaccination group were similar to that in individuals receiving three doses of homologous mRNA-vaccine or a boost of mRNA vaccine after infection, but markedly higher than that in individuals receiving three doses of a homologous inactivated vaccine. This heterologous vaccination regime furthermore significantly enhanced the RBD-specific memory B cell response and S1-specific T cell response, compared to two or three doses of homologous inactivated vaccine. Our study demonstrates that mRNA vaccine booster in individuals vaccinated with inactivated vaccines can be highly beneficial, as it markedly increases the humoral and cellular immune responses against the virus, including the Omicron variant.

Date: 2022
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DOI: 10.1038/s41467-022-30340-5

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