Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice DOI Creative Commons
Maria V. Sergeeva, Kirill Vasilev, Ekaterina A. Romanovskaya-Romanko

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 15 - 15

Published: Dec. 28, 2024

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are promising vaccine approach that ensures pronounced local CD8+ T-cellular Here, we describe protective immunomodulating properties an influenza vector FluVec-N carrying C-terminal fragment SARS-CoV-2 nucleoprotein within open reading frame. Methods: We generated several recombinant reverse genetics confirmed vector's genetic stability, antigen expression in vitro, attenuation, immunogenicity mouse model. tested potential intranasal immunization naïve mice seropositive Th2-prone mice, primed aluminium-adjuvanted inactivated SARS-CoV-2. Immune response immunized challenged was analyzed through serological methods flow cytometry. Results: Double reduced weight loss viral load lungs following infection beta variant. Mice alum-adjuvanted coronavirus experienced substantial early eosinophilia during demonstrating signs enhanced disease. A single boost prevented disease enhancement modulating Protection associated formation specific IgA activation virus-specific effector resident lymphocytes lungs. Conclusions: Our study supports vaccines prevent diseases immunopathology.

Language: Английский

UniFluVec influenza vector induces heterosubtypic protection in ferrets after intranasal administration despite high attenuation DOI Creative Commons
Boris Ferko, Artem Krokhin, Vladimir E. Nebolsin

et al.

Microbiology Independent Research Journal (MIR Journal), Journal Year: 2024, Volume and Issue: 11(1)

Published: Jan. 1, 2024

BACKGROUND: Current influenza vaccines primarily elicit strain-specific immunity, providing limited protection against heterologous strains. OBJECTIVE: This study aimed to develop a novel live attenuated vaccine candidate with enhanced broad-spectrum METHODS: A new vector, UniFluVec, was constructed based on the A/Puerto Rico/8/1934 (H1N1) (PR/8/34) strain, incorporating surface antigens from A/Mississippi/10/2013 (H1N1pdm) strain. The NS genomic segment of UniFluVec modified express truncated NS1 protein (124 amino acids) fused conserved sequence HA2 subunit found in both and B viruses. To further enhance attenuation, nep gene PR/8/34 replaced its counterpart A/Singapore/1/57 (H2N2) protective efficacy tested ferrets seasonal A/Saint Petersburg/224/2015 (H3N2) following either single or double immunizations, compared reassortant differing by presence an intact fragment (WTNS1). RESULTS: demonstrated full attenuation ferrets, causing no clinical symptoms, weight loss, fever when administered intranasally at dose 7.8 log 10 EID 50 . Replication nasal tissues significantly reduced control WTNS1 virus. Although elicited lower hemagglutination inhibition (HAI) antibody titers after immunization WTNS1, it accelerated clearance H3N2 virus respiratory tract challenge. effect comparable vaccination superior that observed WTNS1. CONCLUSION: vector excellent safety intranasal administration conferred effective strain immunization.

Language: Английский

Citations

0
Mucosal Immunization with an Influenza Vector Carrying SARS-CoV-2 N Protein Protects Naïve Mice and Prevents Disease Enhancement in Seropositive Th2-Prone Mice DOI Creative Commons
Maria V. Sergeeva, Kirill Vasilev, Ekaterina A. Romanovskaya-Romanko

et al.

Vaccines, Journal Year: 2024, Volume and Issue: 13(1), P. 15 - 15

Published: Dec. 28, 2024

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are promising vaccine approach that ensures pronounced local CD8+ T-cellular Here, we describe protective immunomodulating properties an influenza vector FluVec-N carrying C-terminal fragment SARS-CoV-2 nucleoprotein within open reading frame. Methods: We generated several recombinant reverse genetics confirmed vector's genetic stability, antigen expression in vitro, attenuation, immunogenicity mouse model. tested potential intranasal immunization naïve mice seropositive Th2-prone mice, primed aluminium-adjuvanted inactivated SARS-CoV-2. Immune response immunized challenged was analyzed through serological methods flow cytometry. Results: Double reduced weight loss viral load lungs following infection beta variant. Mice alum-adjuvanted coronavirus experienced substantial early eosinophilia during demonstrating signs enhanced disease. A single boost prevented disease enhancement modulating Protection associated formation specific IgA activation virus-specific effector resident lymphocytes lungs. Conclusions: Our study supports vaccines prevent diseases immunopathology.

Language: Английский

Citations

0