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• W2074007523 abstract "ABSTRACT Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP 3014 ) or wild-type VEE glycoproteins (VRP 3000 ) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP 3000 -based vaccines were protected from SARS-CoV disease, while animals receiving the VRP 3014 -based vaccines were not. The superior protection for the aged observed with VRP 3000 -based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP 3000 vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP 3014 platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future." @default.
• W2074007523 created "2016-06-24" @default.
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• W2074007523 date "2011-01-01" @default.
• W2074007523 modified "2023-09-25" @default.
• W2074007523 title "Successful Vaccination Strategies That Protect Aged Mice from Lethal Challenge from Influenza Virus and Heterologous Severe Acute Respiratory Syndrome Coronavirus" @default.
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• W2074007523 doi "https://doi.org/10.1128/jvi.01805-10" @default.
• W2074007523 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3014161" @default.
• W2074007523 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20980507" @default.
• W2074007523 hasPublicationYear "2011" @default.
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