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Shaofeng Deng et al.
Summary: Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies.
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Summary: T cell immunity plays a central role in controlling SARS-CoV-2 infection, with early responses correlating with protection. T cell memory provides broad recognition of viral proteins, limiting the impact of viral variants and offering protection against severe disease. Current COVID-19 vaccines elicit robust T cell responses, contributing to the prevention of hospitalization or death. Therefore, the importance of T cell immunity may have been underestimated.
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Immunology
Kerri Hagemann et al.
Summary: In the context of COVID-19, the role of NK cells in the immune response has not been well understood. This study demonstrates that antibodies induced by SARS-CoV-2 infection and anti-SARS-CoV-2 vaccines can activate NK cells, leading to significant immune responses. These findings contribute to a better understanding of the role of NK cells in COVID-19.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2022)
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Isabel Leroux-Roels et al.
Summary: OVX836, a vaccine targeting influenza nucleoprotein, demonstrated safety and immunogenicity in a Phase 1 study. It outperformed the reference vaccine in terms of immunological parameters related to nucleoprotein and showed potential in reducing influenza-like illness episodes.
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Summary: This study reports a nucleoside-modified mRNA vaccine expressing the viral nucleoprotein, which shows modest control of SARS-CoV-2 when administered alone. However, combining this vaccine with a clinically proven mRNA vaccine expressing the spike protein induces robust protection against both Delta and Omicron variants.
SCIENCE TRANSLATIONAL MEDICINE
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Holly A. Fryer et al.
Summary: Natural infection with SARS-CoV-2 induces a stable and long-lasting memory B cell population. Different vaccines have varying capacities to induce immune responses, with mRNA vaccines generating higher antibody levels. However, all vaccines induce spike and RBD-specific Bmem, providing long-term protection.
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Tanushree Dangi et al.
Summary: This study demonstrates that nucleocapsid-specific antibodies can enhance control of SARS-CoV-2 infection and mediate antibody-dependent cellular cytotoxicity against infected cells. These findings provide a rationale for evaluating nucleocapsid-based monoclonal antibody therapies for the treatment of COVID-19.
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Kathryn A. Ryan et al.
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NATURE COMMUNICATIONS
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Elodie Monchatre-Leroy et al.
Summary: This study conducted intranasal SARS-CoV-2 infection experiments in ferrets and hamsters, finding that hamsters were more susceptible to severe illness than ferrets under 103 pfu infection conditions. The viral RNA was detected in the lungs of hamsters but not in ferrets, and in the brain of both species. However, the clinical disease in both species remained mild overall, with the virus becoming undetectable within 14 days post-inoculation.
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Stuart Dowall et al.
Summary: This study utilized hamsters as an experimental animal model to investigate virus transmission dynamics, demonstrating variations in disease levels and kinetics among infected animals within a natural transmission cage system. The results suggest the utility of this natural transmission model for further studies on virus strains and intervention evaluations in a system that closely mimics human infection.
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Anusha Nathan et al.
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William E. Matchett et al.
Summary: Vaccination with a human adenovirus type 5 vector expressing the SARS-CoV-2 nucleocapsid (N) protein can establish protective immunity and reduce weight loss and viral load in vaccinated Syrian hamsters and K18hACE2 mice. Vaccinated mice showed rapid N-specific T cell recall responses in the respiratory mucosa. This study supports the idea of including additional viral antigens in SARS-CoV-2 vaccines to broaden epitope coverage and immune effector mechanisms.
JOURNAL OF IMMUNOLOGY
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Neil C. Dalvie et al.
Summary: Subunit vaccines based on recombinant proteins are crucial tools for controlling COVID-19 due to their low manufacturing cost, scalability, and proven safety and efficacy. Engineered RBD variants exhibit high manufacturability and immunogenicity, showing enhanced immune responses after a single dose and cross-reactivity to new variants of concern.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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Tanushree Dangi et al.
Summary: Incorporating nucleocapsid as an antigen in SARS-CoV-2 vaccines can improve acute protection in both the lungs and brain, suggesting the inclusion of nucleocapsid in next-generation COVID-19 vaccines is warranted. This finding provides important insights for the development of future vaccines against COVID-19.
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Pierre Bessiere et al.
Summary: Type I interferons play a crucial role in the host's response to viral infections, with delayed or impaired signaling correlating with severe COVID-19. Early administration of exogenous type I IFN has shown benefits in treating SARS-CoV-2, whereas late intervention is ineffective but does not lead to harmful effects. These findings are significant for interpreting clinical trials investigating the use of type I IFNs in COVID-19 patients.
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Immunology
Judith Del Campo et al.
Summary: OVX836, a recombinant protein vaccine, induces a strong immune response through intramuscular injection, resulting in a high number of IFN- γ-producing CD8 + T-cells and lung TRM CD8 + T-cells for long-term protection against influenza viruses.
FRONTIERS IN IMMUNOLOGY
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Alba Grifoni et al.
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Sin Fun Sia et al.
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Julian Braun et al.
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Masaki Imai et al.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
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