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