ABSTRACT
Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as T cell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines. Our study provides a favorable approach for developing MPXV-specific vaccines by using a circular mRNA platform and opens up novel avenues for future vaccine research.
Subject(s)
Antibodies, Neutralizing , Monkeypox virus , RNA, Circular , Vaccinia virus , Animals , Mice , Vaccinia virus/genetics , Vaccinia virus/immunology , RNA, Circular/genetics , Antibodies, Neutralizing/immunology , Monkeypox virus/immunology , Monkeypox virus/genetics , Antibodies, Viral/immunology , Vaccinia/prevention & control , Vaccinia/immunology , Mpox (monkeypox)/prevention & control , Mpox (monkeypox)/immunology , Viral Vaccines/immunology , Viral Vaccines/genetics , Humans , Disease Models, Animal , Female , T-Lymphocytes/immunology , T-Lymphocytes/metabolismABSTRACT
Nipah virus (NiV) is a zoonotic paramyxovirus in the genus Henipavirus that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans. Here, based on self-assembled ferritin nanoparticles (FeNPs), we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG (residues 71-602, FeNP-sG) and Ghead (residues 182-602, FeNP-Ghead) onto E. coli-expressed FeNPs (FeNP-sG and FeNP-Ghead, respectively) through Spycatcher/Spytag technology. Compared with sG and Ghead alone, FeNP-sG and FeNP-Ghead elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice, whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-Ghead group. These results further demonstrate that sG possesses greater antigenicity than Ghead and that FeNPs can dramatically enhance immunogenicity. Furthermore, FeNP-sG provided 100% protection against NiV challenge in a hamster model when it was administered twice at a dose of 5 µg/per animal. Our study provides not only a promising candidate vaccine against NiV, but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.
ABSTRACT
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.