Immunology: Optimization of mRNA SARS-CoV-2 vaccine candidate improves protection in macaques

The second generation of the CureVac mRNA vaccine for SARS-CoV-2 shows improved immune responses in nonhuman primates compared with the first iteration, a study in Nature reports. Planned clinical trials for this vaccine will determine whether the improvements will translate into increased efficacy in humans. The research also identifies a way to optimize future mRNA vaccines.

The first generation of the CureVac COVID-19 vaccine, CVnCoV, has recently been evaluated in a phase IIb/III efficacy trial in humans, with an observed vaccine efficacy against symptomatic COVID-19 of approximately 48%. The second-generation vaccine, CV2CoV, has been modified to improve the expression of viral antigens. To determine whether these modifications might improve efficacy, Dan Barouch and colleagues compare both vaccines in nonhuman primates.

Cynomolgus macaques were immunized with either CVnCoV or CV2CoV, or were sham controls (6 macaques per group). CV2CoV induced enhanced immune responses relative to CVnCoV, and improved B and T cell responses. CV2CoV offered improved protection against SARS-CoV-2 infection, with markedly lower viral loads in the upper and lower respiratory tract compared with those of the monkeys that received CVnCoV. In addition, the second-generation vaccine induced a stronger neutralizing antibody response against SARS-CoV-2 variants, including the Delta variant. The authors also found that CV2CoV produced neutralizing antibody responses that were comparable to that induced by the BNT162b2 (Pfizer) vaccine in macaques.

Both the first and second generation of this vaccine candidate carry mRNA that encodes the spike protein of the SARS-CoV-2 virus. The modifications to the second generation optimized noncoding regions of the genetic material to improve protein expression, which improved the protective effects of CV2CoV, the authors conclude.