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Generation and Assembly of Virus-Specific Nucleocapsids of the Respiratory Syncytial Virus
Published on: July 27, 2021
Sub-nucleocapsid nanoparticles: a nasal vaccine against respiratory syncytial virus
Xavier Roux1, Catherine Dubuquoy, Guillaume Durand
1Unité de Virologie et Immunologie Moléculaires (UR892), INRA, Jouy-en-Josas, France.
Insights
A novel intranasal vaccine using respiratory syncytial virus (RSV) nucleoprotein (N) nanoparticles (N SRS) shows promise. This RSV vaccine candidate elicits strong immunity and protects mice against RSV infection, offering a potential new strategy for preventing infant bronchiolitis.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- Respiratory syncytial virus (RSV) bronchiolitis is a significant global health issue in infants, with no current vaccine.
- The RSV nucleoprotein (N) is conserved and targeted by T cell responses but underexplored as a vaccine antigen.
- Recombinant N protein self-assembles into homogeneous nanoparticles (N SRS) enclosing bacterial RNA.
Purpose of the Study:
- To evaluate the vaccine potential of N SRS against RSV infection.
- To assess the immunogenicity and protective efficacy of N SRS in a mouse model.
Main Methods:
- BALB/c mice were immunized intranasally with N SRS and an adjuvant (LT(R192G)).
- Mice were challenged with RSV to assess protection against viral replication.
- Immune responses, including antibody titers and T cell populations, were analyzed.
Main Results:
- N SRS vaccination largely protected mice from RSV replication in the lungs.
- Vaccinated mice exhibited mild airway inflammation.
- Intranasal immunization induced robust local and systemic immunity, including anti-N antibodies (IgG1, IgG2a, IgA) and antigen-specific CD8+ T cells and IFN-gamma+ CD4+ T cells.
Conclusions:
- N SRS represents the first nanoparticle-based intranasal vaccine candidate for RSV.
- This approach demonstrates efficient and safe protection against RSV infection in a preclinical model.
- N SRS holds potential as a novel vaccine strategy for preventing RSV disease.
Background:
Bronchiolitis caused by the respiratory syncytial virus (RSV) in infants less than two years old is a growing public health concern worldwide, and there is currently no safe and effective vaccine. A major component of RSV nucleocapsid, the nucleoprotein (N), has been so far poorly explored as a potential vaccine antigen, even though it is a target of protective anti-viral T cell responses and is remarkably conserved between human RSV A and B serotypes. We recently reported a method to produce recombinant N assembling in homogenous rings composed of 10-11 N subunits enclosing a bacterial RNA. These nanoparticles were named sub-nucleocapsid ring structure (N SRS).
Methodology And Principal Findings:
The vaccine potential of N SRS was evaluated in a well-characterized and widely acknowledged mouse model of RSV infection. BALB/c adult mice were immunized intranasally with N SRS adjuvanted with the detoxified E. coli enterotoxin LT(R192G). Upon RSV challenge, vaccinated mice were largely protected against virus replication in the lungs, with a mild inflammatory lymphocytic and neutrophilic reaction in their airways. Mucosal immunization with N SRS elicited strong local and systemic immunity characterized by high titers of IgG1, IgG2a and IgA anti-N antibodies, antigen-specific CD8(+) T cells and IFN-gamma-producing CD4(+) T cells.
Conclusions/Significance:
This is the first report of using nanoparticles formed by the recombinant nucleocapsid protein as an efficient and safe intra-nasal vaccine against RSV.
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