20980507
not annotated - annotated - LINNAEUS only
Successful vaccination strategies that protect aged mice from lethal challenge from influenza virus and heterologous severe acute respiratory syndrome coronavirus.
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.
Ann file
T1 Species 52 56 mice
N1 Reference T1 Taxonomy:10090
T2 Species 117 162 severe acute respiratory syndrome coronavirus
N2 Reference T2 Taxonomy:694009
T3 Species 284 290 humans
N3 Reference T3 Taxonomy:9606
T4 Species 389 434 severe acute respiratory syndrome coronavirus
N4 Reference T4 Taxonomy:694009
T5 Species 436 444 SARS-CoV
N5 Reference T5 Taxonomy:694009
T6 Species 861 897 Venezuelan equine encephalitis virus
N6 Reference T6 Taxonomy:11036
T7 Species 899 902 VEE
N7 Reference T7 Taxonomy:11036
T8 Species 1076 1079 VEE
N8 Reference T8 Taxonomy:11036
T9 Species 1124 1128 mice
N9 Reference T9 Taxonomy:10090
T10 Species 1159 1167 SARS-CoV
N10 Reference T10 Taxonomy:694009
T11 Species 1250 1258 SARS-CoV
N11 Reference T11 Taxonomy:694009
T12 Species 1916 1931 West Nile virus
N12 Reference T12 Taxonomy:11082
T13 Species 84 99 influenza virus
N13 Reference T13 Taxonomy:11320 Influenza A virus
T14 Species 461 476 influenza virus
N14 Reference T14 Taxonomy:11320 Influenza A virus
T15 Species 1433 1448 influenza virus
N15 Reference T15 Taxonomy:11320 Influenza A virus
T16 Species 1933 1948 influenza virus
N16 Reference T16 Taxonomy:11320 Influenza A virus