Bivalent mRNA vaccine targeting S-protein (CureVac)

The 2022 mpox outbreak led the World Health Organization (WHO) to declare it a public health emergency of international concern (PHEIC). There is a need to develop more effective and safer mpox virus (MPXV)-specific vaccines in response to the mpox epidemic. The mRNA vaccine is a promising platform to protect against MPXV infection. In this study, we construct two bivalent MPXV mRNA vaccines, designated LBA (B6R-A29L) and LAM (A35R-M1R), and a quadrivalent mRNA vaccine, LBAAM (B6R-A35R-A29L-M1R). The immunogenicity and protective efficacy of these vaccines alone or in combination were evaluated in a lethal mouse model. All mRNA vaccine candidates could elicit potential antigen-specific humoral and cellular immune responses and provide protection against vaccinia virus (VACV) infection. The protective effect of the combination of two bivalent mRNA vaccines and the quadrivalent vaccine was superior to that of the individual bivalent mRNA vaccine. Our study provides valuable insights for the development of more efficient and safer mRNA vaccines against mpox.

In a world grappling with the evolving variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), another emerging respiratory virus, respiratory syncytial virus (RSV), continues to cause significant illness in millions of vulnerable people, including infants, elderly individuals, and immunocompromised people globally.The situation is further complicated by the occurrence of co-infections with these viruses, which significantly worsens clin. outcomes and increases mortality rates in children.In a recent article published in Mol. Therapy , Wu et al. 3 describe the development of a bivalent mRNA vaccine encoding two prefusion stabilized forms of antigen (SARS-CoV-2 Omicron spike [S] and the RSV fusion [F] proteins) delivered with lipid nanoparticles (SF-LNPs).The examination of antigen expression and immune responses in monovalent vs. bivalent vaccines, administered at equivalent doses, revealed that SF-LNPs provided robust protection against both RSV and SARS-CoV-2 Omicron infections in mouse and hamster models following immunization.Notably, this study uncovered a novel approach for addressing antigenic competition in bivalent vaccines culminating in the development of a vaccine capable of simultaneously safeguarding against two distinct infectious diseases.Present approaches aimed at improving the breadth of durable broad cross-reactive immunity against Omicron subvariants using S-domain-based vaccines or multivalent vaccines and dendritic cell targeting LNP systems are increasingly garnering attention.These considerations in re-designing the bivalent mRNA vaccine could enhance vaccine efficacy to combat SARS-CoV-2, RSV, and their variants.