Intranasal co-delivery of measles virus and mumps virus expressing nucleocapsid and prefusion spike proteins enhances protection against SARS-CoV-2 infection 2659

Description While current SARS-CoV-2 vaccines have lowered the risk of death associated with COVID-19 disease, SARS-CoV-2 continues to mutate leading to new Variants of Concern (VoC). These mutations, focused in the S protein, can often lead to immune evasiveness, leaving current vaccines ineffective and leading to more investigation of more conserved proteins as potential antigens such as the nucleocapsid (N). In this study, we generated a bivalent live attenuated virus using mumps (MuV) Jeryl Lynn 2 (JL2) strain as a viral vector to express the N protein in combination with MuV-JL2 expressing WA1, the ancestral strain of SARS-CoV-2, or MuV-JL1 expressing XBB 1.5 spike protein stabilized by 6 prolines. The MuV-JL2-N co-delivered with MuV-JL2-WA1 was not only able to induce high anti-N and anti-WA1 S-specific antibodies but also resident memory T cells in the lungs of immunized IFNAR-/- mice. When MuV-JL2-N was co-delivered intranasally with MuV-JL1-XBB 1.5 in golden Syrian hamsters, hamsters could also induce high anti-N and anti-S XBB 1.5 IgG antibodies. When challenged against the Omicron JN.1 variant, hamsters immunized with the bivalent vaccine exhibited no viral titer in the lungs as opposed to hamsters immunized with either MuV-JL2-N and MuV-JL1-XBB 1.5 monovalent vaccines, which had an average viral titer of log 4.7 and log 3.5, respectively. Therefore, co-delivery of MuV-JL2-N and MuV-JL1-XBB 1.5 intranasally enhances protection against SARS-CoV-2 variants such as JN.1. Funding Sources NIH GR135608 Topic Categories Vaccines and Immunotherapy (VAC)