Prefusion F-Based Polyanhydride Nanovaccine Induces Both Humoral and Cell-Mediated Immunity Resulting in Long-Lasting
Laura M Stephens1, Kathleen A Ross2,3, Kody A Waldstein1
1Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA.
Insights
A new nanovaccine (RSVNanoVax) using a stabilized respiratory syncytial virus (RSV) fusion protein shows promise. Intranasal vaccination in mice provided long-lasting protection against RSV infection and reduced lung damage.
Area of Science:
- Virology
- Immunology
- Nanotechnology
- Vaccine Development
Background:
- Respiratory syncytial virus (RSV) causes significant global morbidity, mortality, and economic burden, particularly in young children and older adults.
- Currently, no licensed vaccine is available to prevent RSV infection, highlighting an unmet medical need.
Purpose of the Study:
- To develop and evaluate a novel nanovaccine, RSVNanoVax, for respiratory syncytial virus (RSV) prevention.
- To assess the immunogenicity and protective efficacy of the RSVNanoVax in a mouse model.
Main Methods:
- Development of RSVNanoVax comprising a prefusion-stabilized RSV F protein (DS-Cav1) and a CpG adjuvant within polyanhydride nanoparticles.
- Prime-boost intranasal administration of RSVNanoVax in BALB/c mice followed by RSV challenge.
- Evaluation of protection through weight monitoring, assessment of pulmonary dysfunction, viral load determination, and immunological assays (T cells and antibodies).
Main Results:
- RSVNanoVax administration significantly alleviated weight loss and pulmonary dysfunction post-RSV challenge.
- Protection was durable, maintained for at least 6 months post-vaccination.
- Vaccinated mice demonstrated rapid viral clearance in the lungs and induced robust tissue-resident memory T cells (CD4 and CD8) and neutralizing antibodies against the RSV F protein.
Conclusions:
- The developed prefusion RSV F nanovaccine (RSVNanoVax) elicits a strong and durable immune response.
- RSVNanoVax represents a promising candidate for a new respiratory syncytial virus (RSV) vaccine.
Abstract:
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in both young children and in older adults. Despite the morbidity, mortality, and high economic burden caused by RSV worldwide, no licensed vaccine is currently available. We have developed a novel RSV vaccine composed of a prefusion-stabilized variant of the fusion (F) protein (DS-Cav1) and a CpG oligodeoxynucleotide adjuvant encapsulated within polyanhydride nanoparticles, termed RSVNanoVax. A prime-boost intranasal administration of RSVNanoVax in BALB/c mice significantly alleviated weight loss and pulmonary dysfunction in response to an RSV challenge, with protection maintained up to at least 6 mo postvaccination. In addition, vaccinated mice exhibited rapid viral clearance in the lungs as early as 2 d after RSV infection in both inbred and outbred populations. Vaccination induced tissue-resident memory CD4 and CD8 T cells in the lungs, as well as RSV F-directed neutralizing Abs. Based on the robust immune response elicited and the high level of durable protection observed, our prefusion RSV F nanovaccine is a promising new RSV vaccine candidate.
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