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Recombinant influenza H7 hemagglutinin containing CFLLC minidomain in the transmembrane domain showed enhanced cross-protection in mice
- Source :
- Virus research. 242
- Publication Year :
- 2017
-
Abstract
- Since February 2013, H7N9 influenza virus, causing human infections with high mortality in China, has been a potential pandemic threat. The H7N9 viruses are found to diverge into distinct genotypes as other influenza viruses; thus a vaccine that can provide sufficient cross-protection against different genotypes of H7N9 viruses is urgently needed. Our previous studies demonstrated that the HA-based structural design approach by introducing a CFLLC minidomain into transmembrane domain (TM) of H1, H5 or H9 hemagglutinin (HA) proteins by replacing with H3 subtype HA TM could enhance their cross-protection. In this study, we used Sf9 insect cell expression system to express recombinant H7 HA proteins H7-53WT, in which HA gene was derived from H7N9-53 strain, and H7-53TM containing CFLLC minidomian by replacing its TM domain with H3 HA TM. We investigated whether introduction of CFLLC minidomain into H7 HA (H7-53TM) could increase its cross-reactivity and cross-protection against different genotypes of H7N9 viruses. The results showed that the H7-53TM either with or without squalene adjuvant induced increased HI antibodies, serum IgG antibodies, and IFN-γ production to a panel of 7 H7N9 viruses in mice. Vaccinated animals with H7-53TM alone showed complete protection against challenge with heterologous H7N9-MCX strain, while H7-53WT alone showed incomplete protection (80%). Furthermore, mice vaccinated with H7-53TM HA showed less body weight loss and less pulmonary lesions and inflammation after challenge with homologous or heterologous H7N9 viruses, comparing to H7-53WT. In summary, this study presents a better subunit vaccine candidate (H7-53TM) against potential H7N9 pandemic.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
Cross Protection
Heterologous
Hemagglutinin (influenza)
Hemagglutinin Glycoproteins, Influenza Virus
Biology
Cross Reactions
Spodoptera
medicine.disease_cause
Antibodies, Viral
Virus
Microbiology
law.invention
03 medical and health sciences
Interferon-gamma
Mice
Orthomyxoviridae Infections
law
Virology
medicine
Influenza A virus
Sf9 Cells
Animals
Lung
Vaccines, Synthetic
Body Weight
Hemagglutination Inhibition Tests
Transmembrane domain
Disease Models, Animal
030104 developmental biology
Infectious Diseases
Influenza Vaccines
Immunoglobulin G
Vaccines, Subunit
Recombinant DNA
biology.protein
Leukocytes, Mononuclear
Antibody
Adjuvant
Subjects
Details
- ISSN :
- 18727492
- Volume :
- 242
- Database :
- OpenAIRE
- Journal :
- Virus research
- Accession number :
- edsair.doi.dedup.....4cf98caf1b459e4a2783c2279bb9c2f8