title: Subpopulations in aMPV vaccines are unlikely to be the only cause of reversion to virulence.
abstract: Avian metapneumovirus (aMPV) infects respiratory and reproductive tracts of domestic poultry, often involving secondary infections, and leads to serious economic losses in most parts of the world. While in general disease is effectively controlled by live vaccines, reversion to virulence of those vaccines has been demonstrated on several occasions. Consensus sequence mutations involved in the process have been identified in more than one instance. In one previous subtype A aMPV candidate vaccine study, small subpopulations were implicated. In the current study, the presence of subpopulations in a subtype B vaccine was investigated by deep sequencing. Of the 19 positions where vaccine (strain VCO3/50) and progenitor (strain VCO3/60616) consensus sequences differed, subpopulations were found to have sequence matching progenitor sequence in 4 positions. However none of these mutations occurred in a virulent revertant of that vaccine, thereby demonstrating that the majority progenitor virus population had not survived the attenuation process, hence was not obviously involved in any return to virulence. However within the vaccine, a single nucleotide variation was found which agreed with consensus sequence of a derived virulent revertant virus, hence this and other undetected, potentially virulent subpopulations, can be involved in reversion. Much deeper sequencing of progenitor, vaccine and revertant may clarify whether problematic virulent subpopulations are present and therefore whether these need to be routinely removed during aMPV vaccine preparation prior to registration and release.
authors: Department of Animal Medicine, Production and Health, University of Padua, Viale dell'università, 16, 35020 Legnaro, PD, Italy. Electronic address: giovanni.franzo@unipd.it.
authors: G
authors: G
authors: Franzo
authors: Department of Infection Biology, University of Liverpool, Leahurst Campus, Neston, Cheshire CH64 7TE, United Kingdom.
authors: C J
authors: CJ
authors: Naylor
authors: Department of Animal Medicine, Production and Health, University of Padua, Viale dell'università, 16, 35020 Legnaro, PD, Italy.
authors: M
authors: M
authors: Drigo
authors: INRA and Université de Toulouse, INP, ENVT, UMR 1225 IHAP, F-31076 Toulouse, France.
authors: G
authors: G
authors: Croville
authors: INRA and Université de Toulouse, INP, ENVT, UMR 1225 IHAP, F-31076 Toulouse, France.
authors: M F
authors: MF
authors: Ducatez
authors: Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, 40064 Ozzano Emilia, BO, Italy.
authors: E
authors: E
authors: Catelli
authors: Department of Veterinary Medical Sciences, University of Bologna, Via Tolara di Sopra, 50, 40064 Ozzano Emilia, BO, Italy.
authors: A
authors: A
authors: Laconi
authors: Department of Animal Medicine, Production and Health, University of Padua, Viale dell'università, 16, 35020 Legnaro, PD, Italy.
authors: M
authors: M
authors: Cecchinato
mesh_terms: D000818:Animals; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D029121:Metapneumovirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D009154:Mutation; D012367:RNA, Viral / Q000235:genetics; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D014765:Viral Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics*; D014774:Virulence
chemical_list: D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014765:Viral Vaccines
keywords: Avian metapneumovirus; NGS; Reversion to virulence; Vaccine; Viral subpopulation