Three SARS-CoV-2 spike protein variants delivered intranasally by measles and mumps vaccines are broadly protective

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 3, 2024

Abstract As the new SARS-CoV-2 Omicron variants and subvariants emerge, there is an urgency to develop intranasal, broadly protective vaccines. Here, we developed highly efficacious, intranasal trivalent vaccine candidates (TVC) based on three components of MMR vaccine: measles virus (MeV), mumps (MuV) Jeryl Lynn (JL1) strain, MuV JL2 strain. Specifically, MeV, MuV-JL1, MuV-JL2 strains, each expressing prefusion spike (preS-6P) from a different variant concern (VoC), were combined generate TVCs. Intranasal immunization IFNAR1 −/− mice female hamsters with TVCs generated high levels S-specific serum IgG antibodies, broad neutralizing mucosal IgA antibodies as well tissue-resident memory T cells in lungs. The immunized protected challenge original WA1, B.1.617.2, B.1.1.529 strains. preexisting MeV immunity does not significantly interfere efficacy TVC. Thus, platform promising next-generation candidate.

Language: Английский

A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(41)

Published: Oct. 5, 2023

As SARS-CoV-2 variants of concern (VoCs) that evade immunity continue to emerge, next-generation adaptable COVID-19 vaccines which protect the respiratory tract and provide broader, more effective, durable protection are urgently needed. Here, we have developed one such approach, a highly efficacious, intranasally delivered, trivalent measles-mumps-SARS-CoV-2 spike (S) protein (MMS) vaccine candidate induces robust systemic mucosal with broad protection. This is based on three components MMR vaccine, measles virus Edmonston two mumps strains [Jeryl Lynn 1 (JL1) JL2] known safe, long-lasting protective immunity. The six proline-stabilized prefusion S (preS-6P) genes for ancestral WA1 important VoCs (Delta Omicron BA.1) were each inserted into these viruses then combined “MMS” vaccine. Intranasal immunization MMS in IFNAR1 −/− mice induced strong SARS-CoV-2-specific serum IgG response, cross-variant neutralizing antibodies, IgA, tissue-resident T cells. Immunization golden Syrian hamsters similarly high levels antibodies efficiently neutralized provided complete against challenge any VoCs. an broadly candidate, readily new variants, built platform 50-y safety record also protects mumps.

Language: Английский

Measles Virus-Based Vaccine Expressing Membrane-Anchored Spike of SARS-CoV-2 Inducing Efficacious Systemic and Mucosal Humoral Immunity in Hamsters

Viruses, Journal Year: 2024, Volume and Issue: 16(4), P. 559 - 559

Published: April 3, 2024

As SARS-CoV-2 continues to evolve and COVID-19 cases rapidly increase among children adults, there is an urgent need for a safe effective vaccine that can elicit systemic mucosal humoral immunity limit the emergence of new variants. Using Chinese Hu191 measles virus (MeV-hu191) strain as backbone, we developed MeV chimeras stably expressing prefusion forms either membrane-anchored, full-length spike (rMeV-preFS), or its soluble secreted trimers with help SP-D trimerization tag (rMeV-S+SPD) Omicron BA.2. The two candidates were administrated in golden Syrian hamsters through intranasal subcutaneous routes determine optimal immunization route challenge. delivery rMeV-S+SPD induced more robust IgA antibody response than route. by rMeV-preFS routine was slightly higher route, but no significant difference. stimulated administration. In hamsters, administration elicited high levels NAbs, protecting against BA.2 variant challenge reducing loads diminishing pathological changes vaccinated animals. Encouragingly, sera collected from group consistently showed significantly neutralizing titers latest XBB.1.16. These data suggest highly promising candidate has great potential be into bivalent vaccines (MeV/SARS-CoV-2).

Language: Английский