Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Autor: Kai Wu, Carole Henry, Charis Palandjian, Sarah O’Connell, Angela Woods, Darin K. Edwards, Anna Hill, Hamilton Bennett, Naveen Nunna, Elisabeth Narayanan, Samantha Falcone, Matthew A. Koch, Andrea Carfi, Robert A. Seder, Diana Lee, Guillaume Stewart-Jones, LingZhi Ma, Barney S. Graham, Angela Choi, Tonya M. Colpitts, Kizzmekia S. Corbett, Adrian B. McDermott, Sayda Elbashir, Julian Quinones, Hardik Jani
Rok vydání: 2021
Předmět:
PsVN
pseudovirus neutralization titer
ID50
inhibitory dilution factor
GMT
geometric mean titer
Booster dose
Disease
Antibodies
Viral
ns
not significant
Neutralization
mRNA-1273
Mice
Pandemic
SARS-CoV-2 variants of concern
NHPs
non-human primates
VOI
variant of interest
Medicine
Neutralizing antibody
booster dose
Vaccines
Synthetic
Booster (rocketry)
ACE2
angiotensin converting enzyme 2
LNP
lipid nanoparticle
biology
Vaccination
ELISA
enzyme-linked immunosorbent assay
Nab
neutralizing antibody
UTR
untranslated region
Titer
Infectious Diseases
Molecular Medicine
mRNA Vaccines
2019-nCoV Vaccine mRNA-1273
S
spike
VSV
vesicular stomatitis virus
COVID-19 Vaccines
IgG
immunoglobulin G
PBS
phosphate-buffered saline
Vaccine Efficacy
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
Article
RBD
receptor binding domain
Immunity
Animals
Humans
NTD
N-terminal domain
VOC
variant of concern
General Veterinary
General Immunology and Microbiology
SARS-CoV-2
business.industry
Public Health
Environmental and Occupational Health
TMB
tetramethylbenzidine
COVID-19
primary series
neutralization
Vaccine efficacy
RLUs
relative luminescence units
Virology
biology.protein
business
Zdroj: bioRxiv
Vaccine
ISSN: 0264-410X
DOI: 10.1016/j.vaccine.2021.11.001
Popis: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic that has led to more than 2.8 million deaths worldwide. Safe and effective vaccines are now available, including Moderna’s COVID-19 vaccine (mRNA-1273) that showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. mRNA-1273 encodes for a prefusion stabilized full length spike (S) protein of the Wuhan-Hu-1 isolate. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several emerging variants have shown decreased susceptibility to neutralization by vaccine induced immunity, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of two updated COVID-19 mRNA vaccines designed to target emerging SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with 2-doses of mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization in mice. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies.
Databáze: OpenAIRE
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