A Capsid Virus-Like Particle-Based SARS-CoV-2 Vaccine Induces High Levels of Antibodies and Protects Rhesus Macaques

Ariane Volkmann1, Gerrit Koopman2, Petra Mooij2, Ernst J. Verschoor2, Babs E. Verstrepen2, Willy Bogers2, Manja Idorn3, Søren R. Paludan3, Søren Vang4, Morten A. Nielsen5,6, Adam F. Sander7,5,6, Carolin Schmittwolf1, Hubertus Hochrein1, Paul Chaplin8
1Bavarian Nordic GmbH, Martinsried, Germany
2Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, Netherlands
3Department of Biomedicine, Aarhus University, Aarhus, Denmark
4Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark
5Centre for Medical Parasitology at Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
6Department of Infectious Disease, Copenhagen University Hospital, Copenhagen, Denmark
7AdaptVac Aps, Hørsholm, Denmark
8Bavarian Nordic A/S, Hellerup, Denmark

Tóm tắt

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic. Here, we present non-human primate immunogenicity and protective efficacy data generated with the capsid virus-like particle (cVLP)-based vaccine ABNCoV2 that has previously demonstrated immunogenicity in mice. In rhesus macaques, a single vaccination with either 15 or 100 μg ABNCoV2 induced binding and neutralizing antibodies in a dose-dependent manner, at levels comparable to those measured in human convalescents. A second vaccine administration led to a >50-fold increase in neutralizing antibodies, with 2-log higher mean levels in the 100-μg ABNCoV2 group compared with convalescent samples. Upon SARS-CoV-2 challenge, a significant reduction in viral load was observed for both vaccine groups relative to the challenge control group, with no evidence of enhanced disease. Remarkably, neutralizing antibody titers against an original SARS-CoV-2 isolate and against variants of concern were comparable, indicating a potential for broad protection afforded by ABNCoV2, which is currently in clinical testing.

Từ khóa


Tài liệu tham khảo

2021, WHO Coronavirus (COVID-19) Dashboard 2021

Madhi, 2021, Efficacy of the ChAdOx1 Ncov-19 Covid-19 Vaccine Against the B.1.351 Variant, N Engl J Med, 384, 10.1056/NEJMoa2102214

Shinde, 2021, Efficacy of NVX-CoV2373 Covid-19 Vaccine Against the B.1.351 Variant, N Engl J Med, 384, 10.1056/NEJMoa2103055

Scobie, 2021, Update on Emerging SARS-CoV-2 Variants and Vaccine Considerations, Coronavirus Disease 2019 (COVID-19) Vaccines

Fougeroux, 2021, Capsid-Like Particles Decorated With the SARS-CoV-2 Receptor-Binding Domain Elicit Strong Virus Neutralization Activity, Nat Commun, 12, 324, 10.1038/s41467-020-20251-8

Qian, 2020, Recent Progress on the Versatility of Virus-Like Particles, Vaccines (Basel), 8, 10.3390/vaccines8010139

Proschel, 2017, Probing the Potential of CnaB-Type Domains for the Design of Tag/Catcher Systems, PloS One, 12, 10.1371/journal.pone.0179740

Tan, 2016, Kinetic Controlled Tag-Catcher Interactions for Directed Covalent Protein Assembly, PloS One, 11, 10.1371/journal.pone.0165074

Zakeri, 2012, Peptide Tag Forming a Rapid Covalent Bond to a Protein, Through Engineering a Bacterial Adhesin, Proc Natl Acad Sci USA, 109, 10.1073/pnas.1115485109

Wolfel, 2020, Virological Assessment of Hospitalized Patients With COVID-2019, Nature, 581, 10.1038/s41586-020-2196-x

Li, 2018, Minimap2: Pairwise Alignment for Nucleotide Sequences, Bioinformatics, 34, 10.1093/bioinformatics/bty191

Grubaugh, 2019, An Amplicon-Based Sequencing Framework for Accurately Measuring Intrahost Virus Diversity Using PrimalSeq and Ivar, Genome Biol, 20, 8, 10.1186/s13059-018-1618-7

Rambaut, 2020, A Dynamic Nomenclature Proposal for SARS-CoV-2 Lineages to Assist Genomic Epidemiology, Nat Microbiol, 5, 10.1038/s41564-020-0770-5

Khalil, 2021, Chemokines and Chemokine Receptors During COVID-19 Infection, Comput Struct Biotechnol J, 19, 10.1016/j.csbj.2021.01.034

Wang, 2021, Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7, Nature, 593, 10.1038/s41586-021-03398-2

Garcia-Beltran, 2021, Multiple SARS-CoV-2 Variants Escape Neutralization by Vaccine-Induced Humoral Immunity, Cell, 184, 2372, 10.1016/j.cell.2021.03.013

Chackerian, 2020, Factors That Govern the Induction of Long-Lived Antibody Responses, Viruses, 12, 74, 10.3390/v12010074

Liao, 2020, Single-Cell Landscape of Bronchoalveolar Immune Cells in Patients With COVID-19, Nat Med, 26, 10.1038/s41591-020-0901-9

Nienhold, 2020, Two Distinct Immunopathological Profiles in Autopsy Lungs of COVID-19, Nat Commun, 11, 5086, 10.1038/s41467-020-18854-2

Corbett, 2020, Evaluation of the mRNA-1273 Vaccine Against SARS-CoV-2 in Nonhuman Primates, N Engl J Med, 383, 10.1056/NEJMoa2024671

Vogel, 2021, BNT162b Vaccines Protect Rhesus Macaques From SARS-CoV-2, Nature, 592, 10.1038/s41586-021-03275-y

van Doremalen, 2020, ChAdOx1 Ncov-19 Vaccine Prevents SARS-CoV-2 Pneumonia in Rhesus Macaques, Nature, 586, 10.1038/s41586-020-2608-y

Mercado, 2020, Single-Shot Ad26 Vaccine Protects Against SARS-CoV-2 in Rhesus Macaques, Nature, 586, 10.1038/s41586-020-2607-z

Polack, 2020, Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine, N Engl J Med, 383, 10.1056/NEJMoa2034577

Khoury, 2021, Neutralizing Antibody Levels are Highly Predictive of Immune Protection From Symptomatic SARS-CoV-2 Infection, Nat Med, 27, 10.1038/s41591-021-01377-8

Earle, 2021, Evidence for Antibody as a Protective Correlate for COVID-19 Vaccines, Vaccine, 39, 10.1016/j.vaccine.2021.05.063

Addetia, 2020, Neutralizing Antibodies Correlate With Protection From SARS-CoV-2 in Humans During a Fishery Vessel Outbreak With a High Attack Rate, J Clin Microbiol, 58, 10.1128/JCM.02107-20

Feng, 2021, Correlates of Protection Against Symptomatic and Asymptomatic SARS-CoV-2 Infection, Nat Med, 27, 10.1101/2021.06.21.21258528

Chen, 2021, Resistance of SARS-CoV-2 Variants to Neutralization by Monoclonal and Serum-Derived Polyclonal Antibodies, Nat Med, 27, 10.1038/s41591-021-01294-w

Wang, 2021, mRNA Vaccine-Elicited Antibodies to SARS-CoV-2 and Circulating Variants, Nature, 592, 10.3410/f.739524179.793585051

Wu, 2021, Serum Neutralizing Activity Elicited by mRNA-1273 Vaccine, N Engl J Med, 384, 10.1056/NEJMc2102179

Liu, 2021, Neutralizing Activity of BNT162b2-Elicited Serum, N Engl J Med, 384, 10.1056/NEJMc2102017

Zhou, 2021, Evidence of Escape of SARS-CoV-2 Variant B.1.351 From Natural and Vaccine-Induced Sera, Cell, 184, 2348, 10.1016/j.cell.2021.02.037

Lustig, 2021, Neutralising Capacity Against Delta (B.1.617.2) and Other Variants of Concern Following Comirnaty (BNT162b2, BioNTech/Pfizer) Vaccination in Health Care Workers, Israel, Euro Surveill, 26, 10.2807/1560-7917.ES.2021.26.26.2100557

Planas, 2021, Reduced Sensitivity of SARS-CoV-2 Variant Delta to Antibody Neutralization, Nature, 596, 10.1038/s41586-021-03777-9

Abu-Raddad, 2021, Effectiveness of the BNT162b2 Covid-19 Vaccine Against the B.1.1.7 and B.1.351 Variants, N Engl J Med, 385, 10.1056/NEJMc2104974

Sadoff, 2021, Safety and Efficacy of Single-Dose Ad26.Cov2.S Vaccine Against Covid-19, N Engl J Med, 384, 10.1056/NEJMoa2101544