About: Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge

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About: Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge Goto Sponge NotDistinct Permalink

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Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge
Creator	De Gregorio, Ennio Bertholet, Sylvie Brazzoli, Michela Cecchi, Raffaella Giovani, Cinzia Maccari, Silvia Magini, Diletta Mangiavacchi, Simona Geall, Andrew Ulmer, Jeffrey
Source	PMC
abstract	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 (T(CM)) and effector memory (T(EM)) 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.
has issue date	2016-08-15(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0161193
bibo:pmid	27525409
has license	cc-by
sha1sum (hex)	d26fb6227fcc98e9e8f9fecbedfd47bc4c00e7ba
schema:url	https://doi.org/10.1371/journal.pone.0161193
resource representing a document's title	Self-Amplifying mRNA Vaccines Expressing Multiple Conserved Influenza Antigens Confer Protection against Homologous and Heterosubtypic Viral Challenge
has PubMed Central identifier	PMC4985159
has PubMed identifier	27525409
schema:publication	PLoS One
resource representing a document's body	covid:d26fb6227fcc98e9e8f9fecbedfd47bc4c00e7ba#body_text
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