Journal article
Long-Lasting Protection Induced by a Polyanhydride Nanovaccine against Respiratory Syncytial Virus in an Outbred Mouse Model
Journal of virology, Vol.96(22), e01502-22
10/31/2022
DOI: 10.1128/jvi.01502-22
PMCID: PMC9683007
PMID: 36314826
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.
Details
- Title: Subtitle
- Long-Lasting Protection Induced by a Polyanhydride Nanovaccine against Respiratory Syncytial Virus in an Outbred Mouse Model
- Creators
- Laura M. Stephens - University of IowaKathleen A. Ross - Iowa State UniversityJason S. McLellan - The University of Texas at AustinBalaji Narasimhan - Iowa State UniversitySteven M. Varga - University of Iowa
- Contributors
- Rebecca Ellis Dutch (Editor)
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.96(22), e01502-22
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/jvi.01502-22
- PMID
- 36314826
- PMCID
- PMC9683007
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Number of pages
- 14
- Grant note
- ISU | Nanovaccine Institute, Iowa State University (Nanovaccine Institute) (https://doi.org/10.13039/100015389) T32 CA078586 / HHS | NIH | National Cancer Institute (NCI) (https://doi.org/10.13039/100000054) R01 AI124093 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (https://doi.org/10.13039/100000060) T32 AI007485 / HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) (https://doi.org/10.13039/100000060)
- Language
- English
- Date published
- 10/31/2022
- Academic Unit
- Graduate College Admin and Gen; Microbiology and Immunology; Pathology
- Record Identifier
- 9984307657402771
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