Development of a chimeric bat influenza A virus as a live vaccine

Abstract: Zoonotic transmission of influenza A virus (IAV) from poultry represent a
constant threat for the human population. Effective IAV live vaccines that can
be used in poultry would lower the risk of such transmissions, however, the risk
of reassortment with circulating avian IAV prevented the development of such
vaccines. Using the reassortment-incompement bat IAV, we developed novel
live vaccines, designated R65mono/H17N10, harboring the internal gene
segments of H17N10 and the surface glycoproteins HA and NA of the avian
H5N1 strain R65. Vaccination with R65mono/H17N10 protected chicken as well
as ferrets from lethal homologous challenge with wildtype R65. However, there
are some restrictions, since this vaccine is only poorly replicating in chicken,
whereas spread of this virus in ferrets was very efficient and caused the
infection of contact ferrets. Incorporation of avian-adaptive mutations in the
H17N10 backbone that increase viral growth in avian cells but reduce spread in
mammalian cells would be beneficial for the further development of such live
vaccines. To identify such mutations, we passaged of R65mono/H17N10 in
embryonated eggs and day-old chicks and identified mutations in HA (A201E,
V273A and G339R), M1 (D156N), the viral polymerase subunits PB2 (I382S),
PB1 (Q694H, I695K) and PA (E141K). The individual mutations in the
polymerase subunits increased viral growth in avian cells, whereas both the HA
and M1 mutations showed no effect. Consistent with a species-specific
adaption, the mutations in the polymerase subunits impaired viral growth in
mammalian cells and mice. Subsequent insertion of the PB1, PB2 or PA
mutations into the background of a human prototypic IAV (A/PR8) severely
affected the polymerase activity and viral growth in human cells but not in avian
cells. Especially the mutation I382S in PB2 located in the cap binding domain,
appeared to impair viral replication but not transcription. The identification of
these avian-adaptive mutations might be instrumental for the future
development of H17N10-based live vaccines

Objekt anzeigen

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2020

Klassifikation und Themen

• Schlagwort: Influenza

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2020
• Urheber: Ran, Wei
• Beteiligte Personen und Organisationen: Schwemmle, Martin ; Albert-Ludwigs-Universität Freiburg. Fakultät für Biologie

Weitere Informationen

• URN: urn:nbn:de:bsz:25-freidok-1656123
• Rechteinformation: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.