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Updated: Mar 30, 2026
Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice
Published on: February 22, 2019
Intranasal immunisation with recombinant adenovirus vaccines protects against a lethal challenge with pneumonia virus
Helen E Maunder1, Geraldine Taylor2, Keith N Leppard1
1School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
Abstract:
Pneumonia virus of mice (PVM) infection of BALB/c mice induces bronchiolitis leading to a fatal pneumonia in a dose-dependent manner, closely paralleling the development of severe disease during human respiratory syncytial virus infection in man, and is thus a recognised model in which to study the pathogenesis of pneumoviruses. This model system was used to investigate delivery of the internal structural proteins of PVM as a potential vaccination strategy to protect against pneumovirus disease. Replication-deficient recombinant human adenovirus serotype 5 (rAd5) vectors were constructed that expressed the M or N gene of PVM pathogenic strain J3666. Intranasal delivery of these rAd5 vectors gave protection against a lethal challenge dose of PVM in three different mouse strains, and protection lasted for at least 20 weeks post-immunisation. Whilst the PVM-specific antibody response in such animals was weak and inconsistent, rAd5N primed a strong PVM-specific CD8(+) T cell response and, to a lesser extent, a CD4(+) T cell response. These findings suggest that T-cell responses may be more important than serum IgG in the observed protection induced by rAd5N.
Insights
This study explored using adenovirus vectors to deliver PVM genes as a vaccine. Intranasal delivery of these vectors protected mice against lethal pneumonia, suggesting T-cell responses are key for protection.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Pneumonia virus of mice (PVM) in BALB/c mice serves as a model for human respiratory syncytial virus (hRSV) infection.
- PVM infection causes dose-dependent bronchiolitis and fatal pneumonia.
Purpose of the Study:
- To investigate the potential of delivering PVM internal structural proteins via adenovirus vectors as a vaccination strategy.
- To evaluate protection against PVM disease using recombinant adenovirus serotype 5 (rAd5) vectors expressing PVM M or N genes.
Main Methods:
- Replication-deficient rAd5 vectors were engineered to express PVM M or N genes.
- Intranasal administration of rAd5 vectors was used for immunization.
- Mice were challenged with a lethal dose of PVM to assess protection.
Main Results:
- Intranasal rAd5 vector delivery conferred protection against lethal PVM challenge in three mouse strains.
- Protection was sustained for at least 20 weeks post-immunization.
- While antibody responses were weak, rAd5N induced strong CD8(+) and moderate CD4(+) T cell responses.
Conclusions:
- T-cell responses, particularly CD8(+) T cells, may play a more significant role than serum IgG in protection against PVM.
- Adenovirus-vectored delivery of PVM genes is a promising vaccination strategy against pneumovirus infections.
