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Updated: Aug 16, 2026
Intranasal Administration of Recombinant Influenza Vaccines in Chimeric Mouse Models to Study Mucosal Immunity
Published on: June 25, 2015
Protection of mice against lethal infection with highly pathogenic H7N7 influenza A virus by using a recombinant
Emmie de Wit1, Vincent J Munster, Monique I J Spronken
1Department of Virology, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
Abstract:
In 2003, an outbreak of highly pathogenic avian influenza occurred in The Netherlands. The avian H7N7 virus causing the outbreak was also detected in 88 humans suffering from conjunctivitis or mild respiratory symptoms and one person who died of pneumonia and acute respiratory distress syndrome. Here we describe a mouse model for lethal infection with A/Netherlands/219/03 isolated from the fatal case. Because of the zoonotic and pathogenic potential of the H7N7 virus, a candidate vaccine carrying the avian hemagglutinin and neuraminidase proteins produced in the context of the high-throughput vaccine strain A/PR/8/34 was generated by reverse genetics and tested in the mouse model. The hemagglutinin gene of the recombinant vaccine strain was derived from a low-pathogenicity virus obtained prior to the outbreak from a wild mallard. The efficacy of a classical nonadjuvanted subunit vaccine and an immune stimulatory complex-adjuvanted vaccine was compared. Mice receiving the nonadjuvanted vaccine revealed low antibody titers, lack of clinical protection, high virus titers in the lungs, and presence of virus in the spleen, liver, kidneys, and brain. In contrast, mice receiving two doses of the immune stimulatory complex-adjuvanted vaccine revealed high antibody titers, clinical protection, approximately 1,000-fold reduction of virus titers in the lungs, and rare detection of the virus in other organs. This is the first report of an H7 vaccine candidate tested in a mammalian model. The data presented suggest that vaccine candidates based on low-pathogenicity avian influenza A viruses, which can be prepared ahead of pandemic threats, can be efficacious if an effective adjuvant is used.
Insights
An H7N7 avian influenza vaccine candidate showed efficacy in a mouse model, particularly when combined with an immune stimulatory complex adjuvant. This finding is crucial for developing pandemic preparedness strategies against avian influenza viruses.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- A 2003 highly pathogenic avian influenza H7N7 outbreak in The Netherlands infected humans, causing mild to severe illness.
- The H7N7 virus demonstrated zoonotic potential, necessitating the development of effective countermeasures.
Purpose of the Study:
- To establish a lethal mouse model for H7N7 avian influenza virus infection.
- To evaluate the efficacy of a candidate H7 vaccine in a mammalian model.
- To compare the effectiveness of adjuvanted versus non-adjuvanted vaccine formulations.
Main Methods:
- A mouse model was developed using a lethal H7N7 avian influenza virus isolate.
- A recombinant H7 vaccine candidate was generated using reverse genetics, incorporating hemagglutinin and neuraminidase genes from low-pathogenicity strains.
- Vaccine efficacy was assessed by comparing non-adjuvanted and immune stimulatory complex (ISC)-adjuvanted formulations in mice challenged with the H7N7 virus.
Main Results:
- The ISC-adjuvanted vaccine elicited high antibody titers and provided clinical protection in mice.
- Mice vaccinated with the adjuvanted vaccine showed a 1,000-fold reduction in lung virus titers and limited systemic viral spread.
- The non-adjuvanted vaccine failed to provide protection, resulting in high viral loads and systemic infection.
Conclusions:
- This study presents the first H7 vaccine candidate tested in a mammalian model.
- Effective adjuvants, such as ISC, are critical for the efficacy of avian influenza vaccine candidates.
- Vaccine strategies based on low-pathogenicity avian influenza viruses can be viable for pandemic preparedness.
