An mpox virus mRNA-lipid nanoparticle vaccine confers protection against lethal orthopoxviral challenge.

Autor: Freyn AW; Moderna Inc., Cambridge, 02139 MA, USA., Atyeo C; Moderna Inc., Cambridge, 02139 MA, USA., Earl PL; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 MD, USA., Americo JL; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 MD, USA., Chuang GY; Moderna Inc., Cambridge, 02139 MA, USA., Natarajan H; Moderna Inc., Cambridge, 02139 MA, USA., Frey TR; Moderna Inc., Cambridge, 02139 MA, USA., Gall JG; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 MD, USA., Moliva JI; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 MD, USA., Hunegnaw R; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 MD, USA., Asthagiri Arunkumar G; Moderna Inc., Cambridge, 02139 MA, USA., Ogega CO; Moderna Inc., Cambridge, 02139 MA, USA., Nasir A; Moderna Inc., Cambridge, 02139 MA, USA., Santos G; Moderna Inc., Cambridge, 02139 MA, USA., Levin RH; Moderna Inc., Cambridge, 02139 MA, USA., Meni A; Moderna Inc., Cambridge, 02139 MA, USA., Jorquera PA; Moderna Inc., Cambridge, 02139 MA, USA., Bennett H; Moderna Inc., Cambridge, 02139 MA, USA., Johnson JA; Moderna Inc., Cambridge, 02139 MA, USA., Durney MA; Moderna Inc., Cambridge, 02139 MA, USA., Stewart-Jones G; Moderna Inc., Cambridge, 02139 MA, USA., Hooper JW; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, 21702 MD, USA., Colpitts TM; Moderna Inc., Cambridge, 02139 MA, USA., Alter G; Moderna Inc., Cambridge, 02139 MA, USA., Sullivan NJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 MD, USA., Carfi A; Moderna Inc., Cambridge, 02139 MA, USA., Moss B; Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, 20892 MD, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2023 Oct 04; Vol. 15 (716), pp. eadg3540. Date of Electronic Publication: 2023 Oct 04.
DOI: 10.1126/scitranslmed.adg3540
Abstrakt: Mpox virus (MPXV) caused a global outbreak in 2022. Although smallpox vaccines were rapidly deployed to curb spread and disease among those at highest risk, breakthrough disease was noted after complete immunization. Given the threat of additional zoonotic events and the virus's evolving ability to drive human-to-human transmission, there is an urgent need for an MPXV-specific vaccine that confers protection against evolving MPXV strains and related orthopoxviruses. Here, we demonstrate that an mRNA-lipid nanoparticle vaccine encoding a set of four highly conserved MPXV surface proteins involved in virus attachment, entry, and transmission can induce MPXV-specific immunity and heterologous protection against a lethal vaccinia virus (VACV) challenge. Compared with modified vaccinia virus Ankara (MVA), which forms the basis for the current MPXV vaccine, immunization with an mRNA-based MPXV vaccine generated superior neutralizing activity against MPXV and VACV and more efficiently inhibited spread between cells. We also observed greater Fc effector T H 1-biased humoral immunity to the four MPXV antigens encoded by the vaccine, as well as to the four VACV homologs. Single MPXV antigen-encoding mRNA vaccines provided partial protection against VACV challenge, whereas multivalent vaccines combining mRNAs encoding two, three, or four MPXV antigens protected against disease-related weight loss and death equal or superior to MVA vaccination. These data demonstrate that an mRNA-based MPXV vaccine confers robust protection against VACV.
Databáze: MEDLINE
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