20962084
not annotated - annotated - LINNAEUS only
Modifications in the polymerase genes of a swine-like triple-reassortant influenza virus to generate live attenuated vaccines against 2009 pandemic H1N1 viruses.
On 11 June 2009, the World Health Organization (WHO) declared that the outbreaks caused by novel swine-origin influenza A (H1N1) virus had reached pandemic proportions. The pandemic H1N1 (H1N1pdm) virus is the predominant influenza virus strain in the human population. It has also crossed the species barriers and infected turkeys and swine in several countries. Thus, the development of a vaccine that is effective in multiple animal species is urgently needed. We have previously demonstrated that the introduction of temperature-sensitive mutations into the PB2 and PB1 genes of an avian H9N2 virus, combined with the insertion of a hemagglutinin (HA) tag in PB1, resulted in an attenuated (att) vaccine backbone for both chickens and mice. Because the new pandemic strain is a triple-reassortant (TR) virus, we chose to introduce the double attenuating modifications into a swine-like TR virus isolate, A/turkey/OH/313053/04 (H3N2) (ty/04), with the goal of producing live attenuated influenza vaccines (LAIV). This genetically modified backbone had impaired polymerase activity and restricted virus growth at elevated temperatures. In vivo characterization of two H1N1 vaccine candidates generated using the ty/04 att backbone demonstrated that this vaccine is highly attenuated in mice, as indicated by the absence of signs of disease, limited replication, and minimum histopathological alterations in the respiratory tract. A single immunization with the ty/04 att-based vaccines conferred complete protection against a lethal H1N1pdm virus infection in mice. More importantly, vaccination of pigs with a ty/04 att-H1N1 vaccine candidate resulted in sterilizing immunity upon an aggressive intratracheal challenge with the 2009 H1N1 pandemic virus. Our studies highlight the safety of the ty/04 att vaccine platform and its potential as a master donor strain for the generation of live attenuated vaccines for humans and livestock.
Ann file
T1 Out-of-scope 43 48;73 88 swine influenza virus
T3 Species 148 160 H1N1 viruses
N3 Reference T3 Taxonomy:11320
T4 Species 261 298 swine-origin influenza A (H1N1) virus
N4 Reference T4 Taxonomy:11320
T5 Out-of-scope 386 401 influenza virus
T6 Species 416 421 human
N6 Reference T6 Taxonomy:9606
T7 Species 500 505 swine
N7 Reference T7 Taxonomy:9823
T8 Species 756 766 H9N2 virus
T9 Species 890 898 chickens
N9 Reference T9 Taxonomy:9031
T10 Species 1043 1048 swine
N10 Reference T10 Taxonomy:9823
T11 Species 1072 1100 A/turkey/OH/313053/04 (H3N2)
N11 Reference T11 Taxonomy:11320
T12 Species 1334 1338 H1N1
N12 Reference T12 Taxonomy:11320
T13 Species 2082 2088 humans
N13 Reference T13 Taxonomy:9606
T14 Species 903 907 mice
T15 Species 1452 1456 mice
T16 Species 1726 1730 mice
N14 Reference T14 Taxonomy:10090 Mus musculus
N15 Reference T15 Taxonomy:10090 Mus musculus
N16 Reference T16 Taxonomy:10090 Mus musculus
N8 Reference T8 Taxonomy:11320
#2 AnnotatorNotes T11 TODO check span: virus related
T17 Species 346 366 H1N1 (H1N1pdm) virus
N17 Reference T17 Taxonomy:11320
T18 Species 1900 1904 H1N1
N18 Reference T18 Taxonomy:11320
T19 Species 1699 1712 H1N1pdm virus
N19 Reference T19 Taxonomy:11320
#4 AnnotatorNotes T19 TODO check span: virus related
T20 Species 1787 1791 H1N1
N20 Reference T20 Taxonomy:11320
#5 AnnotatorNotes T20 TODO check span: virus related
T21 Species 1765 1769 pigs
N21 Reference T21 Taxonomy:9823 Sus scrofa
T2 Species 488 495 turkeys
N2 Reference T2 Taxonomy:9103 Meleagris gallopavo
N1 Reference T1 Taxonomy:11308 Orthomyxoviridae
N5 Reference T5 Taxonomy:11308 Orthomyxoviridae