Concurrent human antibody and TH1 type T-cell responses elicited by a COVID-19 RNA vaccine (original) (raw)

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

doi: https://doi.org/10.1101/2020.07.17.20140533

Abstract

An effective vaccine is needed to halt the spread of the SARS-CoV-2 pandemic. Recently, we reported safety, tolerability and antibody response data from an ongoing placebo-controlled, observer-blinded phase 1/2 COVID-19 vaccine trial with BNT162b1, a lipid nanoparticle (LNP) formulated nucleoside-modified messenger RNA encoding the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Here we present antibody and T cell responses after BNT162b1 vaccination from a second, non-randomized open-label phase 1/2 trial in healthy adults, 18-55 years of age. Two doses of 1 to 50 µg of BNT162b1 elicited robust CD4+ and CD8+ T cell responses and strong antibody responses, with RBD-binding IgG concentrations clearly above those in a COVID-19 convalescent human serum panel (HCS). Day 43 SARS-CoV-2 serum neutralising geometric mean titers were 0.7-fold (1 µg) to 3.5-fold (50 µg) those of HCS. Immune sera broadly neutralised pseudoviruses with diverse SARS-CoV-2 spike variants. Most participants had TH1 skewed T cell immune responses with RBD-specific CD8+ and CD4+ T cell expansion. Interferon (IFN)γ was produced by a high fraction of RBD-specific CD8+ and CD4+ T cells. The robust RBD-specific antibody, T-cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest multiple beneficial mechanisms with potential to protect against COVID-19.

Competing Interest Statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi\_disclosure.pdf and declare: U.S. and O.T. are management board members and employees at BioNTech SE (Mainz, Germany); D.B., C.B., S.B., E.D., A.-K.E., B.F., J.G., R.H., M.-C.K., U.L., V.L., D.M., C.R., J.S. and T.P. are employees at BioNTech SE; K.K., L.M.K., I.V., A.M., J.Q. and M.V. are employees at BioNTech RNA Pharmaceuticals GmbH; M.B. is an employee at Bexon Clinical Consulting LLC. A.B., C.A.K. and K.P. are employees of Regeneron Pharmaceuticals Inc; K.K., A.M., U.S. and O.T. are inventors on patents and patent applications related to RNA technology and COVID-19 vaccine; D.B., C.B., S.B., E.D., J.G., K.K., R.H., A.K.-B., L.M.K., D.L., U.L., A.M., C.R., U.S., O.T., I.V. and M.V. have securities from BioNTech SE; D.C., M.C., P.R.D., K.U.J., W.K., J.L., J.L.P., I.L.S. and K.A.S. are employees at Pfizer and may have securities from Pfizer; C.A.K. is an officer at Regeneron Pharmaceuticals, Inc; A.B., C.A.K. and K.P. have securities from Regeneron Pharmaceuticals, Inc; C.F.-G. and P.-Y.S. received compensation from Pfizer to perform the neutralisation assay; no other relationships or activities that could appear to have influenced the submitted work.

Clinical Trial

NCT04380701

Funding Statement

BioNTech is the Sponsor of the study and responsible for the design, data collection, data analysis, data interpretation, and writing of the report. Pfizer advised on the study and the manuscript, generated serological data, and contracted for the generation of serological data. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit the data for publication. All study data were available to all authors. This study was not supported by any external funding at the time of submission.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The trial was carried out in Germany in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines and with approval by an independent ethics committee (Ethik-Kommission of the Landesaerztekammer Baden-Wuerttemberg, Stuttgart, Germany) and the competent regulatory authority (Paul-Ehrlich Institute, Langen, Germany). All participants provided written informed consent.

All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. Upon completion of this clinical trial, summary-level results will be made public and shared in line with data sharing guidelines.

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