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Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Long-Lasting Protection Induced by a Polyanhydride Nanovaccine against Respiratory Syncytial Virus in an Outbred
Laura M Stephens1, Kathleen A Ross2, Jason S McLellan3
1Interdisciplinary Graduate Program in Immunology, University of Iowagrid.214572.7, Iowa City, Iowa, USA.
Insights
A new intranasal vaccine candidate, RSVNanoVax, shows promise for long-term respiratory syncytial virus (RSV) protection. It generated sustained immune responses and cleared the virus in diverse mouse models, indicating potential for a future RSV vaccine.
Area of Science:
- Immunology
- Vaccinology
- Virology
Background:
- Respiratory syncytial virus (RSV) is a major cause of severe respiratory illness in children, with no licensed vaccine currently available.
- Natural RSV infection provides incomplete long-term immunity, necessitating the development of effective vaccines.
- Existing research has shown initial promise for RSVNanoVax in inbred mice.
Purpose of the Study:
- To evaluate the long-term efficacy of the novel RSVNanoVax vaccine candidate in a genetically diverse mouse model.
- To assess the durability of immune responses induced by intranasal administration of RSVNanoVax.
- To determine the protective capacity of RSVNanoVax against RSV challenge in outbred mice.
Main Methods:
- Development of RSVNanoVax, a vaccine comprising polyanhydride nanoparticles encapsulating the RSV prefusion F protein and a CpG adjuvant.
- Intranasal prime-boost vaccination of outbred Swiss Webster mice with RSVNanoVax.
- Assessment of systemic and mucosal antibody responses (IgG, IgA), neutralizing antibody activity, and viral clearance post-RSV challenge up to one year.
Main Results:
- RSVNanoVax vaccination induced sustained RSV F-specific IgG and IgA antibody titers in serum and respiratory tracts for at least one year.
- Vaccinated mice demonstrated robust neutralizing antibodies against both RSV A and B strains.
- Intranasal vaccination led to rapid viral clearance from the lungs following RSV challenge.
Conclusions:
- RSVNanoVax is a promising vaccine candidate for respiratory syncytial virus (RSV) prevention.
- The vaccine elicits durable, broad-spectrum immunity and protection in a genetically diverse population.
- Intranasal delivery of RSVNanoVax offers a potential strategy for long-term protection against RSV infection.
Abstract:
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children. In humans, natural infection with RSV affords only partial long-term protection from reinfection, and there is no licensed RSV vaccine currently available. We have developed a new vaccine candidate, termed RSVNanoVax, composed of polyanhydride nanoparticles encapsulating the RSV prefusion F protein and a CpG 1668 oligodeoxynucleotide adjuvant. We recently reported that vaccination of inbred BALB/c mice with RSVNanoVax induced both RSV-specific cellular and humoral immunity, which provided protection from viral replication and RSV-induced disease. To further assess the efficacy of RSVNanoVax, here, we utilized outbred Swiss Webster mice to examine vaccine efficacy in a more genetically diverse population. Following intranasal prime-boost vaccination with RSVNanoVax, Swiss Webster mice exhibited robust titers of systemic RSV F-directed IgG antibodies and RSV F-directed IgA within the lungs and nasal passages that were sustained out to at least 1 year post-vaccination. Serum antibodies maintained robust neutralizing activity against both RSV A and B strains. Following RSV challenge, vaccinated Swiss Webster mice exhibited rapid viral clearance from the lungs. Overall, our results indicate that RSVNanoVax represents a promising RSV vaccine candidate capable of providing long-term protection and immunity in a genetically diverse population. IMPORTANCE Respiratory syncytial virus (RSV) infection causes thousands of infections and deaths in children and elderly adults each year. Research in this field is of great importance as there remains no licensed vaccine to prevent RSV infections. We developed a novel vaccine candidate, RSVNanoVax, utilizing the RSV prefusion F protein encapsulated in polyanhydride nanoparticles. Here, we show that the intranasal delivery of RSVNanoVax protected outbred mice from viral replication within the lungs when challenged with RSV out to 1 year post-vaccination. Additionally, RSV-specific antibody responses were generated in both the serum and lung tissue and sustained long-term. These results demonstrate that our vaccine is an encouraging candidate for driving long-term protection in the lungs in a genetically diverse population.

