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An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Evaluation of adenoviral vector Ad19a encoding RSV-F as novel vaccine against respiratory syncytial virus
Jana Fuchs1, Julian Hübner1, Anna Schmidt1
1Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Schlossgarten 4, 91054, Erlangen, Germany.
Insights
New adenoviral vector vaccines offer protection against respiratory syncytial virus (RSV). Intranasal delivery induced protective immunity, but intramuscular delivery with rAd19a vectors caused enhanced disease, highlighting the importance of mucosal immunity for respiratory pathogen vaccines.
Area of Science:
- Virology and Immunology
- Vaccine Development
Background:
- Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in infants.
- Natural RSV infections do not provide lasting immunity, necessitating the development of effective vaccines.
- Adenoviral vectors are being explored for vaccine delivery against respiratory pathogens.
Purpose of the Study:
- To evaluate a novel adenoviral vector (rAd19a) vaccine for respiratory syncytial virus (RSV) immunogenicity and efficacy.
- To compare the performance of rAd19a vectors against the established rAd5 vector.
- To investigate the impact of different immunization routes (intranasal vs. intramuscular) on vaccine-induced immune responses and protection.
Main Methods:
- Mice were primed with DNA vaccines and boosted with either rAd19a or rAd5 vectors encoding the RSV F protein.
- Vaccine immunogenicity was assessed by measuring antibody and T-cell responses.
- Efficacy was evaluated by challenging vaccinated mice with RSV and assessing protection and disease enhancement.
Main Results:
- Both intranasal rAd19a and rAd5 vector boosts provided protection against RSV challenge.
- Intramuscular immunization with rAd19a vectors resulted in vaccine-enhanced disease following RSV infection.
- Intranasal vaccination induced protective mucosal IgA antibodies and tissue-resident memory T-cells, controlling viral replication.
Conclusions:
- Adenoviral vector vaccines encoding the RSV F protein can elicit protective immunity.
- Intranasal delivery promotes protective mucosal immunity, while intramuscular delivery may lead to detrimental immune enhancement.
- Developing effective mucosal vaccines is crucial for combating respiratory pathogens like RSV.
Abstract:
Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infections in infants and toddlers. Since natural infections do not induce persistent immunity, there is the need of vaccines providing long-term protection. Here, we evaluated a new adenoviral vector (rAd) vaccine based on the rare serotype rAd19a and compared the immunogenicity and efficacy to the highly immunogenic rAd5. Given as an intranasal boost in DNA primed mice, both vectors encoding the F protein provided efficient protection against a subsequent RSV infection. However, intramuscular immunization with rAd19a vectors provoked vaccine-enhanced disease after RSV infection compared to non-vaccinated animals. While mucosal IgA antibodies and tissue-resident memory T-cells in intranasally vaccinated mice rapidly control RSV replication, a strong anamnestic systemic T-cell response in absence of local immunity might be the reason for immune-mediated enhanced disease. Our study highlighted the potential benefits of developing effective mucosal against respiratory pathogens.
