Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge
| Autor: | Silvia Maccari, Cinzia Giovani, Ennio De Gregorio, Sylvie Bertholet, Diletta Magini, Simona Mangiavacchi, Michela Brazzoli, Andrew Geall, Jeffrey B. Ulmer, Raffaella Cecchi |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
RNA viruses Viral Diseases Influenza Viruses Physiology lcsh:Medicine Priming (immunology) Gene Expression medicine.disease_cause Pathology and Laboratory Medicine Biochemistry White Blood Cells Mice 0302 clinical medicine Influenza A Virus H1N1 Subtype Animal Cells Immune Physiology Cricetinae Influenza A virus Medicine and Health Sciences Cytotoxic T cell Public and Occupational Health lcsh:Science Antigens Viral Lung Conserved Sequence Vaccines Multidisciplinary Immune System Proteins T Cells Viral Vaccine Viral Core Proteins Vaccination and Immunization Infectious Diseases Medical Microbiology Influenza Vaccines Viral Pathogens Viruses Cellular Types Pathogens Research Article Influenza vaccine Immune Cells Immunology Genetic Vectors Cytotoxic T cells Biology Microbiology Antibodies Cell Line Viral Matrix Proteins 03 medical and health sciences Immune system Antigen Virology medicine Animals RNA Messenger Antigens Microbial Pathogens Blood Cells Influenza A Virus H3N2 Subtype lcsh:R Organisms Gene Amplification Biology and Life Sciences Proteins Viral Vaccines Cell Biology Vaccine efficacy Influenza 030104 developmental biology Vaccines Inactivated lcsh:Q Preventive Medicine 030215 immunology Orthomyxoviruses T-Lymphocytes Cytotoxic |
| Zdroj: | PLoS ONE PLOS ONE PLoS ONE, Vol 11, Iss 8, p e0161193 (2016) |
| ISSN: | 1932-6203 |
| Popis: | Current hemagglutinin (HA)-based seasonal influenza vaccines induce vaccine strain-specific neutralizing antibodies that usually fail to provide protection against mismatched circulating viruses. Inclusion in the vaccine of highly conserved internal proteins such as the nucleoprotein (NP) and the matrix protein 1 (M1) was shown previously to increase vaccine efficacy by eliciting cross-reactive T-cells. However, appropriate delivery systems are required for efficient priming of T-cell responses. In this study, we demonstrated that administration of novel self-amplifying mRNA (SAM®) vectors expressing influenza NP (SAM(NP)), M1 (SAM(M1)), and NP and M1 (SAM(M1-NP)) delivered with lipid nanoparticles (LNP) induced robust polyfunctional CD4 T helper 1 cells, while NP-containing SAM also induced cytotoxic CD8 T cells. Robust expansions of central memory (TCM) and effector memory (TEM) CD4 and CD8 T cells were also measured. An enhanced recruitment of NP-specific cytotoxic CD8 T cells was observed in the lungs of SAM(NP)-immunized mice after influenza infection that paralleled with reduced lung viral titers and pathology, and increased survival after homologous and heterosubtypic influenza challenge. Finally, we demonstrated for the first time that the co-administration of RNA (SAM(M1-NP)) and protein (monovalent inactivated influenza vaccine (MIIV)) was feasible, induced simultaneously NP-, M1- and HA-specific T cells and HA-specific neutralizing antibodies, and enhanced MIIV efficacy against a heterologous challenge. In conclusion, systemic administration of SAM vectors expressing conserved internal influenza antigens induced protective immune responses in mice, supporting the SAM® platform as another promising strategy for the development of broad-spectrum universal influenza vaccines. |
| Databáze: | OpenAIRE |
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