Better COVID-19 Defense

Next generation mRNA vaccine shows improved protection against disease

Illustration of MRNA chains contained in a modern coronavirus vaccine.

Image: MikeMareen / iStock/Getty


This article is part of Harvard Medical School’s continuing coverage of medicine, biomedical research, medical education, and policy related to the SARS-CoV-2 pandemic and the disease COVID-19.

In a recent phase 2b/3 clinical trial, a third mRNA vaccine against COVID-19—known as CVnCoV and developed by CureVac—reported approximately 48 percent efficacy against symptomatic disease.

In a head-to-head test of a revised version of the vaccine, CV2CoV, researchers at Harvard Medical School and Beth Israel Deaconess Medical Center assessed the vaccines’ ability to provoke an immune response, and their protective efficacy against COVID-19 in nonhuman primates.

Their findings, published in Nature, show the modifications made to the second-generation CV2nCoV induced a tenfold higher antibody response than the original version, CVnCoV.

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“We found that CV2CoV elicited substantially higher immune responses and provided significantly improved protective efficacy against SARS-CoV-2, the virus that causes COVID-19, compared with CVnCoV in macaques,” said Dan Barouch, the HMS William Bosworth Castle Professor of Medicine and director of the Center for Virology and Vaccine Research at Beth Israel Deaconess.

“These data suggest that optimizing selected elements of the mRNA backbone can substantially improve the immunogenicity and protective efficacy of mRNA vaccines,” he said. 

Barouch and colleagues' data revealed that, whereas CVnCoV provided only modest reduction in viral loads in immunized animals later challenged with SARS-CoV-2, CV2CoV induced tenfold higher antibody responses and dramatically lowered viral loads.

They also report that CV2CoV induced antigen-specific memory B cell responses and T cell responses. Moreover, CV2CoV raised similar antibody titers in macaques compared with the BNT162b2 vaccine developed by Pfizer.

“The improved characteristics of CV2CoV compared with CVnCoV may translate into increased efficacy in humans, and clinical trials of the second-generation vaccine are planned,” said Barouch, who is a steering committee member of the Ragon Institute of MGH, MIT, and Harvard.

This work was supported by CureVac AG and the German Federal Ministry of Education and Research (BMBF; 01KI20703), the National Institutes of Health (CA260476), the Massachusetts Consortium on Pathogen Readiness, and Ragon Institute of MGH, MIT, and Harvard. Development of CV2CoV is carried out in a collaboration of CureVac AG and GSK. Please see the paper for a complete list of disclosures.

Adapted from a Beth Israel Deaconess news release.