Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice
By
Kai Wu,
Angela Choi,
Matthew Koch,
Sayda Elbashir,
LingZhi Ma,
Diana Lee,
Angela Woods,
Carole Henry,
Charis Palandjian,
Anna Hill,
Hardik Jani,
Julian Quinones,
Naveen Nunna,
Sarah O'Connell,
Adrian B. McDermott,
Samantha Falcone,
Elisabeth Narayanan,
Tonya Colpitts,
Hamilton Bennett,
Kizzmekia Corbett,
Robert Seder,
Barney Graham,
Guillaume B.E. Stewart-Jones,
Andrea Carfi,
Darin K Edwards
Posted 13 Apr 2021
bioRxiv DOI: 10.1101/2021.04.13.439482
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.
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