Safety and immunogenicity of SARS-CoV-2 variant mRNA vaccine boosters in healthy adults: an interim analysis.

Adult Aged Antibodies, Neutralizing / blood Antibodies, Viral / blood COVID-19 / immunology COVID-19 Vaccines / adverse effects Female Healthy Volunteers Humans Immunization, Secondary / adverse effects Immunogenicity, Vaccine Male Middle Aged Preliminary Data RNA, Messenger / adverse effects SARS-CoV-2 / genetics Treatment Outcome United States Vaccination / adverse effects

Journal

Nature medicine

ISSN: 1546-170X

Titre abrégé: Nat Med

Pays: United States

ID NLM: 9502015

Informations de publication

Date de publication:
11 2021

Historique:

received: 22 07 2021

accepted: 02 09 2021

pubmed: 17 9 2021

medline: 15 12 2021

entrez: 16 9 2021

Statut: ppublish

Résumé

The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study ( NCT04405076 ) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups (n = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned (P < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 (P < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing.

Identifiants

DOI: 10.1038/s41591-021-01527-y PMID: 34526698 PMC: PMC8604720

pubmed: 34526698

doi: 10.1038/s41591-021-01527-y

pii: 10.1038/s41591-021-01527-y

pmc: PMC8604720

doi:

Substances chimiques

Antibodies, Neutralizing 0

Antibodies, Viral 0

COVID-19 Vaccines 0

RNA, Messenger 0

Banques de données

ClinicalTrials.gov

['NCT04405076']

Types de publication

Clinical Trial, Phase II Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Langues

eng

Sous-ensembles de citation

Pagination

2025-2031

Commentaires et corrections

Type : CommentIn

Informations de copyright

Références

Pormohammad, A. et al. Efficacy and safety of COVID-19 vaccines: a systematic review and meta-analysis of randomized clinical trials. Vaccines (Basel) 9, 467 (2021).

doi: 10.3390/vaccines9050467

Anderson, E. J. et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N. Engl. J. Med. 383, 2427–2438 (2020).

doi: 10.1056/NEJMoa2028436

Jackson, L. A. et al. An mRNA vaccine against SARS-CoV-2—preliminary report. N. Engl. J. Med. 383, 1920–1931 (2020).

doi: 10.1056/NEJMoa2022483

Chu, L. et al. A preliminary report of a randomized controlled phase 2 trial of the safety and immunogenicity of mRNA-1273 SARS-CoV-2 vaccine. Vaccine 39, 2791–2799 (2021).

doi: 10.1016/j.vaccine.2021.02.007

Baden, L. R. et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N. Engl. J. Med. 384, 403–416 (2021).

doi: 10.1056/NEJMoa2035389

U.S. Food and Drug Administration. Moderna COVID-19 Vaccine. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine (2021).

European Medicines Agency. EMA recommends COVID-19 Vaccine Moderna for authorisation in the EU. https://www.ema.europa.eu/en/news/ema-recommends-covid-19-vaccine-moderna-authorisation-eu (2021).

Moderna announces emergency use listing granted by the World Health Organization for its COVID-19 vaccine. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-emergency-use-listing-granted-world-health (2021).

Centers for Disease Control and Prevention. SARS-CoV-2 Variant Classifications and Definitions. https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html (2021).

Global Initiative on Sharing All Influenza Data (GISAID). GISAID: Overview of Variants in Countries. https://covariants.org/per-country (2021).

Centers for Disease Control and Prevention. COVID Data Tracker: Variant Proportions. https://covid.cdc.gov/covid-data-tracker/#datatracker-home (2021).

Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205–1211 (2021).

doi: 10.1038/s41591-021-01377-8

Turner, J. S. et al. SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. Nature 596, 109–113 (2021).

doi: 10.1038/s41586-021-03738-2

Madhi, S.A. et al. Efficacy of the ChAdOx1 nCoV-19 Covid-19 vaccine against the B.1.351 variant. N. Engl. J. Med. 384, 1885–1898 (2021).

doi: 10.1056/NEJMoa2102214

Shinde, V. et al. Efficacy of NVX-CoV2373 Covid-19 vaccine against the B.1.351 variant. N. Engl. J. Med. 384, 1899–1909 (2021).

doi: 10.1056/NEJMoa2103055

Israel Ministry of Health. Decline in vaccine effectiveness against infection and symptomatic illness. https://www.gov.il/en/Departments/news/05072021-03 (2021).

Choi, A. et al. Serum neutralizing activity of mRNA-1273 against SARS-CoV-2 variants. Preprint at https://www.biorxiv.org/content/10.1101/2021.06.28.449914v1 (2021).

Wu, K. et al. Serum neutralizing activity elicited by mRNA-1273 vaccine. N. Engl. J. Med. 384, 1468–1470 (2021).

doi: 10.1056/NEJMc2102179

Doria-Rose, N. et al. Antibody persistence through 6 months after the second dose of mRNA-1273 vaccine for Covid-19. N. Engl. J. Med. 384, 2259–2261 (2021).

doi: 10.1056/NEJMc2103916

Shen, X. et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral spike vaccines. Cell Host Microbe 29, 529–539 (2021).

doi: 10.1016/j.chom.2021.03.002

Whitt, M. A. Generation of VSV pseudotypes using recombinant DeltaG-VSV for studies on virus entry, identification of entry inhibitors, and immune responses to vaccines. J. Virol. Methods 169, 365–374 (2010).

doi: 10.1016/j.jviromet.2010.08.006