Abstract | UNLABELLED:
Influenza infection causes severe disease and death in humans. In traditional vaccine research and development, a single high-dose virus challenge of animals is used to evaluate vaccine efficacy. This type of challenge model may have limitations. In the present study, we developed a novel challenge model by infecting mice repeatedly in short intervals with low doses of influenza A virus. Our results show that compared to a single high-dose infection, mice that received repeated low-dose challenges showed earlier morbidity and mortality and more severe disease. They developed higher vial loads, more severe lung pathology, and greater inflammatory responses and generated only limited influenza A virus-specific B and T cell responses. A commercial trivalent influenza vaccine protected mice against a single high and lethal dose of influenza A virus but was ineffective against repeated low-dose virus challenges. Overall, our data show that the repeated low-dose influenza A virus infection mouse model is more stringent and may thus be more suitable to select for highly efficacious influenza vaccines. IMPORTANCE:
Influenza epidemics and pandemics pose serious threats to public health. Animal models are crucial for evaluating the efficacy of influenza vaccines. Traditional models based on a single high-dose virus challenge may have limitations. Here, we describe a new mouse model based on repeated low-dose influenza A virus challenges given within a short period. Repeated low-dose challenges caused more severe disease in mice, associated with higher viral loads and increased lung inflammation and reduced influenza A virus-specific B and T cell responses. A commercial influenza vaccine that was shown to protect mice from high-dose challenge was ineffective against repeated low-dose challenges. Overall, our results show that the low-dose repeated-challenge model is more stringent and may therefore be better suited for preclinical vaccine efficacy studies.
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Authors | Yufeng Song, Xiang Wang, Hongbo Zhang, Xinying Tang, Min Li, Jufang Yao, Xia Jin, Hildegund C J Ertl, Dongming Zhou |
Journal | Journal of virology
(J Virol)
Vol. 89
Issue 15
Pg. 7841-51
(Aug 2015)
ISSN: 1098-5514 [Electronic] United States |
PMID | 25995265
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015, American Society for Microbiology. All Rights Reserved. |
Chemical References |
- Antibodies, Viral
- Influenza Vaccines
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Topics |
- Animals
- Antibodies, Viral
(immunology)
- Chick Embryo
- Disease Models, Animal
- Female
- Humans
- Influenza A Virus, H1N1 Subtype
(genetics, immunology, physiology)
- Influenza Vaccines
(administration & dosage, immunology)
- Influenza, Human
(immunology, pathology, prevention & control, virology)
- Lung
(immunology, pathology, virology)
- Mice
- Mice, Inbred C57BL
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