COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

Şahin, Uğur; Muik, Alexander; Derhovanessian, Evelyna; Vogler, Isabel; Kranz, Lena M.; Vormehr, Mathias; Baum, Alina; Pascal, Kristen E.; Quandt, Jasmin; Maurus, Daniel; Brachtendorf, Sebastian; Lörks, Verena; Sikorski, Julian; Hilker, Rolf; Becker, Dirk; Eller, Ann Kathrin; Grützner, Jan; Boesler, Carsten; Rosenbaum, Corinna; Kühnle, Marie Cristine; Luxemburger, Ulrich; Kemmer-Brück, Alexandra; Langer, David; Bexon, Martin; Bolte, Stefanie; Karikó, Katalin; Palanche, Tania; Fischer, Boris; Schultz, Armin; Shi, Pei Yong; Fontes-Garfias, Camila R.; Perez, John L.; Swanson, Kena A.; Loschko, Jakob; Scully, Ingrid L.; Cutler, Mark; Kalina, Warren V.; Kyratsous, Christos A.; Cooper, David A.; Dormitzer, Philip R.; Jansen, Kathrin U.; Türeci, Özlem

doi:10.1038/s41586-020-2814-7

Cited by 1,734 publications

(1,791 citation statements)

References 35 publications

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“…However, local and systemic reactions seen after priming doses in these groups were comparable to those seen in the ChAdOx1 nCoV-19 participants in the phase 1/2 trial as previously reported 17 , suggesting this group is representative of the wider trial population. The observation of reduced second-dose reactogenicity is in contrast to reported profiles of two mRNA vaccines for COVID-19 and a protein-adjuvant vaccine technology, in which, although generally well tolerated, reactogenicity increased with the second dose 4,18,24 . This phenomenon is noteworthy since it is conceivable that additional doses may be required in the future to sustain immunity.…”

Section: Discussioncontrasting

confidence: 87%

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Barrett

Belij‐Rammerstorfer

Dold

et al. 2020

Nat Med

283

253

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Section: Discussioncontrasting

confidence: 87%

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Barrett

Belij‐Rammerstorfer

Dold

et al. 2020

Nat Med

283

253

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“…T cell responses were not reported in this study (Mulligan et al, 2020). BNT162b1 vaccination not only induced high titers of neutralizing antibodies but also elicited robust antigen specific CD4 + and CD8 + T cell responses (Sahin et al, 2020). A second form of the BNT162 COVID-19 vaccine, b2, has been tested clinically in comparison to BNT162b1 (Walsh et al, 2020).…”

Section: Progress Of Covid-19 Vaccine Developmentmentioning

confidence: 71%

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

Zhang

Zhan

et al. 2020

Sci. China Life Sci.

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The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients’ outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

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“…While soluble monomeric RBD protein suffered from limited immunogenicity, a tandem repeat single chain construct enhanced immunogenicity (Dai et al, 2020). A soluble trimeric RBD, as applied in the BNT162b1 mRNA vaccine, showed promising immunogenicity in clinical trials, including stimulation of antibodies and T cell responses (Mulligan et al, 2020; Sahin et al, 2020). In addition to trimerization, membrane anchoring seems to further improve immunogenicity, as transmembrane anchored full-length S prefusion-stabilized protein was reported to elicit higher VNA levels than corresponding secreted constructs (Corbett et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

Hennrich

Banda

Oberhuber

et al. 2020

Preprint

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The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which may cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients. Boost immunization with the identical replicon further enhanced neutralizing activity. These results demonstrate that rhabdovirus minispike replicons represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen.

show abstract

COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses

Cited by 1,734 publications

References 35 publications

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

Safe and effective two-in-one replicon-and-VLP minispike vaccine for COVID-19

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