Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity against prevalent SARS-CoV-2 variants

被引：78

作者：

Gross, Ruediger ^{[1
]}

Zanoni, Michelle ^{[1
]}

Seidel, Alina ^{[1
]}

Conzelmann, Carina ^{[1
]}

Gilg, Andrea ^{[1
]}

Krnavek, Daniela ^{[1
]}

Erdemci-Evin, Suemeyye ^{[1
]}

Mayer, Benjamin ^{[2
]}

Hoffmann, Markus ^{[3
,4
]}

Poehlmann, Stefan ^{[3
,4
]}

Liu, Weimin ^{[5
,6
]}

Hahn, Beatrice H. ^{[5
,6
]}

Beil, Alexandra ^{[7
]}

Kroschel, Joris ^{[7
]}

Jahrsdoerfer, Bernd ^{[8
,9
,10
]}

Schrezenmeier, Hubert ^{[8
,9
,10
]}

Kirchhoff, Frank ^{[1
]}

Muench, Jan ^{[1
,11
]}

Mueller, Janis A. ^{[1
]}

机构：

[1] Ulm Univ, Inst Mol Virol, Med Ctr, D-89081 Ulm, Germany

[2] Ulm Univ, Inst Epidemiol & Med Biometry, Ulm, Germany

[3] German Primate Ctr, Leibniz Inst Primate Res, Infect Biol Unit, Gottingen, Germany

[4] Georg August Univ Gottingen, Fac Biol & Psychol, Gottingen, Germany

[5] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA

[6] Univ Penn, Dept Med, Philadelphia, PA 19104 USA

[7] Univ Hosp Ulm, Cent Dept Clin Chem, D-89081 Ulm, Germany

[8] Ulm Univ, Inst Transfus Med, D-89081 Ulm, Germany

[9] German Red Cross Blood Serv Baden Wurttemberg Hes, Inst Clin Transfus Med & Immunogenet Ulm, D-89081 Ulm, Germany

[10] Univ Hosp Ulm, D-89081 Ulm, Germany

[11] Ulm Univ, Core Facil Funct Peptid, Med Ctr, D-89081 Ulm, Germany

来源：

EBIOMEDICINE | 2022年 / 75卷

基金：

欧盟地平线“2020”; 美国国家卫生研究院;

关键词：

B.1.617.2; COVID-19; Delta; heterologous vaccination; immunity;

D O I：

10.1016/j.ebiom.2021.103761

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. Methods To evaluate the reactogenicity and humoral as well as cellular immune responses towards most prevalent SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, we analysed a cohort of 26 clinic employees aged 25-46 (median 30.5) years who received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8-week interval. Serological data were compared to a cohort which received homologous BNT162b2 vaccination with a 3-week interval (14 individuals aged 25-65, median 42). Findings Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and more severe than after the BNT162b2 boost. Antibody titres increased significantly over time resulting in strong neutralization titres two weeks after the BNT162b2 boost and subsequently slightly decreased over the course of 17 weeks. At the latest time point measured, all analysed sera retained neutralizing activity against the currently dominant Delta (B.1.617.2) variant. Two weeks post boost, neutralizing activity against the Alpha (B.1.1.7) and immuneevading Beta (B.1.351) variant was similar to 4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was observed in neutralization of Kappa (B.1.617.1). In addition, heterologous vaccination induced CD4(+) and CD8(+) T cells reactive to SARS-CoV-2 spike peptides of all analysed variants; Wuhan-Hu-1, Alpha, Beta, Gamma (P.1), and Delta. Interpretation In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination is not associated with serious adverse events and induces potent humoral and cellular immune responses. The Alpha, Beta, Delta, and Kappa variants of spike are potently neutralized by sera from all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations and also offers protection against current variants of concern. Copyright (C) 2021 The Author(s). Published by Elsevier B.V.

引用

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