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Protection against homo and hetero-subtypic influenza A virus by optimized M2e DNA vaccine
- Source :
- Emerging Microbes & Infections
- Publication Year :
- 2019
- Publisher :
- Informa UK Limited, 2019.
-
Abstract
- Current influenza vaccines provide hemagglutinin strain-specific protection, but rarely provide cross-protection against divergent strains. It is, therefore, particularly important to develop a universal vaccine against conserved proteins or conserved regions of the virus. In this study, we used N-terminal extracellular region of the influenza virus M2 protein (M2e) as the target antigen and constructed two optimized M2e DNA vaccines (p-tPA-p3M2e and p-p3M2e) with increased antigenic epitope density and enhanced antigen secretion. Both vaccines induced high M2e-specific humoral and cellular immune responses in the vaccinated mice. These two vaccines also conferred protection against a lethal infection of homo-subtypic H1N1 virus, with p-tPA-p3M2e being the most effective. In addition, p-tPA-p3M2e also showed cross-protection against different subtypes of the influenza virus (H9N2, H6N6, and H10N8) at varying rates (80%, 40%, and 20%, respectively). After passive immunization, M2e DNA vaccine-induced antibodies in the sera provided complete protection against homologous virus challenge. An analysis of the mechanism underlying this immunization-mediated protection indicates that M2e-specific IgG and T-cell immune responses may play critical roles in the prevention of infection and viral clearance. Taken together, our results indicate that this optimized M2e DNA vaccine is a promising candidate for the development of a universal, broad-spectrum influenza virus vaccine.
- Subjects :
- 0301 basic medicine
Epidemiology
Cross Protection
030106 microbiology
Immunology
Hemagglutinin (influenza)
Biology
Microbiology
Virus
Article
DNA vaccination
Madin Darby Canine Kidney Cells
Viral Matrix Proteins
03 medical and health sciences
Mice
Dogs
Influenza A Virus, H1N1 Subtype
Orthomyxoviridae Infections
Virology
Universal influenza vaccine
Influenza, Human
Drug Discovery
Vaccines, DNA
Animals
Humans
tPA
Immunity, Cellular
Immunization, Passive
General Medicine
Influenza
Immunity, Humoral
body regions
030104 developmental biology
HEK293 Cells
Infectious Diseases
M2e
Influenza Vaccines
biology.protein
Parasitology
optimized M2e DNA vaccine
Subjects
Details
- ISSN :
- 22221751
- Volume :
- 8
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Emerging Microbes & Infections
- Accession number :
- edsair.doi.dedup.....ad708c5eee04bcfc8b530df70630ec53
- Full Text :
- https://doi.org/10.1080/22221751.2018.1558962