Abstract
More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18–55 years (NCT04324606). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.
| Original language | English |
|---|---|
| Pages (from-to) | 279- |
| Number of pages | 28 |
| Journal | Nature Medicine |
| Volume | 27 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 17 Dec 2020 |
Bibliographical note
Funding Information:The funder had no role in the design, execution or analysis of this study. This report is independent research funded by the National Institute for Health Research (NIHR). The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care (DHSC). Additional resources for study delivery were provided by NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre; University Hospital Southampton NHS Foundation Trust; the NIHR Imperial Clinical Research Facility; and NIHR North West London, South London, Wessex and West of England Local Clinical Research Networks; and NIHR Oxford Health Biomedical Research Centre. P.M.F. received funding from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (finance code 001). The control vaccine was provided free of charge by the UK DHSC. The authors are grateful to the volunteers who participated in this study. The investigators express their gratitude for the contribution of all the trial participants, the invaluable advice of the international DSMB (Supplementary Information) and the independent members of the trial steering committee. We are grateful for the advice and intellectual support from K.S. Campbell (Institute for Cancer Research, Philadelphia) with the NK cell line culture and use. The authors are grateful to the senior management at AstraZeneca for facilitating and funding the manufacture of the AZD1222 vaccine candidate, the pseudovirus neutralization assays and Meso Scale antibody assay used in this study. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. Finally, we acknowledge UKRI, NIHR, CEPI, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical Research Network and AstraZeneca.
Funding Information:
The University of Oxford has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. S.C.G. is cofounder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1 vector-based vaccines and a patent application covering this SARS-CoV-2 vaccine. T.L. is named as an inventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project. P.M.F. is a consultant to Vaccitech. A.J.P. is Chair of the UK DHSC Joint Committee on Vaccination & Immunisation but does not participate in discussions on COVID-19 vaccines, and is a member of the Strategic Advisory Group of Experts on Immunization to the WHO (World Health Organization). A.J.P. is an NIHR senior investigator. The views expressed in this article do not necessarily represent the views of the DHSC, Joint Committee on Vaccination & Immunisation, NIHR or WHO. A.V.S.H. reports personal fees from Vaccitech, outside the submitted work, and has a patent ChAdOx1 licensed to Vaccitech, and may benefit from royalty income to the University of Oxford from sales of this vaccine by AstraZeneca and sublicensees. M.S. reports grants from the NIHR; nonfinancial support from AstraZeneca; grants from Janssen, GlaxoSmithKline, MedImmune and Novavax; grants and nonfinancial support from Pfizer; and grants from MCM, outside the submitted work. C.G. reports personal fees from the Duke Human Vaccine Institute, outside the submitted work. A.D.D. reports grants and personal fees from AstraZeneca, outside the submitted work. In addition, A.D.D. has a patent manufacturing process for ChAdOx vectors with royalties paid to AstraZeneca and a patent ChAdOx2 vector with royalties paid to AstraZeneca. The other authors declare no competing interests.
Publisher Copyright:
© 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
Keywords
- DOUBLE-BLIND
- HIGH-THROUGHPUT
- HIV-1 VACCINE
- PROTECTION
- IMMUNITY
- ASSAY
- DISEASE
- ADULTS
