Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic. Safe and effective COVID-19 vaccines are now available, including mRNA-1273, which has shown 94% efficacy in prevention of symptomatic COVID-19 disease. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several variants have shown decreased susceptibility to neutralization by vaccine-induced immunity, most notably B.1.351 (Beta), although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of 2 updated mRNA vaccines designed to target SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the spike protein found in B.1.351 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 mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against B.1.351, while mRNA-1273.211 was effective at providing broad cross-variant neutralization. A third (booster) 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 being evaluated in pre-clinical challenge and clinical studies.
Competing Interest Statement
K.W., A.C., M.C., S.E., L.M., D.L., A.W., C.H., C.P., A.H., H.J., J.Q., N.N., S.F., E.N., T.C., H.B., G.B.E.S.-J., A.C., and D.K.E. are employees of and shareholders in Moderna Inc.
- Abbreviations
- ACE2
- angiotensin converting enzyme 2
- ELISA
- enzyme-linked immunosorbent assay
- GMT
- geometric mean titer
- ID50
- inhibitory dilution factor
- IgG
- immunoglobulin G
- LNP
- lipid nanoparticle
- Nab
- neutralizing antibody
- NHPs
- non-human primates
- ns
- not significant
- NTD
- N-terminal domain
- PBS
- phosphate-buffered saline
- PsVN
- pseudovirus neutralization titer
- RBD
- receptor binding domain
- RLUs
- relative luminescence units
- S
- spike
- SARS-CoV-2
- severe acute respiratory syndrome coronavirus 2
- TMB
- tetramethylbenzidine
- UTR
- untranslated region
- VOC
- variant of concern
- VOI
- variant of interest
- VSV
- vesicular stomatitis virus