Evidence for positive selection of hepatitis A virus antigenic variants in vaccinated men-having-sex-with men patients : Implications for immunization policies
Sabrià, Aurora (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Gregori i Font, Josep (Roche Diagnostics SL)
Garcia-Cehic, D. (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Guix, Susana (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Pumarola Suñé, Tomàs (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Manzanares-Laya, Sandra (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Caylà, Joan A.. (Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública)
Bosch, Albert (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Quer, Josep 1963- (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas)
Pintó, Rosa (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)

Fecha:	2018
Resumen:	A huge outbreak in the men-having-sex-with-men (MSM) has hit Europe during the years 2016-2018. Outbreak control has been hampered by vaccine shortages in many countries, and to minimize their impact, reduction of antigen doses has been implemented. However, these measures may have consequences on the evolution of hepatitis A virus (HAV), leading to the emergence of antigenic variants. Cases in vaccinated MSM patients have been detected in Barcelona, opening the possibility to study HAV evolution under immune pressure. We performed deep-sequencing analysis of ten overlapping fragments covering the complete capsid coding region of HAV. A total of 14578255 reads were obtained and used for the analysis of virus evolution in vaccinated versus non-vaccinated patients. We estimated maximum and minimum mutation frequencies, and Shannon entropy in the quasispecies of each patient. Non-synonymous (NSyn) mutations affecting residues exposed in the capsid surface were located, with respect to epitopes, using the recently described crystal structure of HAV, as an indication of its potential role in escaping to the effect of vaccines. HAV evolution at the quasispecies level, in non-vaccinated and vaccinated patients, revealed higher diversity in epitope-coding regions of the vaccinated group. Although amino acid replacements occurring in and around the epitopes were observed in both groups, their abundance was significantly higher in the quasispecies of vaccinated patients, indicating ongoing processes of fixation. Our data suggest positive selection of antigenic variants in some vaccinated patients, raising concerns for new vaccination polices directed to the MSM group.
Ayudas:	Ministerio de Economía y Competitividad BIO2014-53285-R Ministerio de Economía y Competitividad BIO2017-83191-R Ministerio de Economía y Competitividad PI16/00337 Instituto de Salud Carlos III IDI-20151125
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Vaccine escape-mutants ; MSM ; Quasispecies ; Deep-sequencing
Publicado en:	EBioMedicine, Vol. 39 (november 2018) , p. 348-357, ISSN 2352-3964

DOI: 10.1016/j.ebiom.2018.11.023
PMID: 30472089

10 p, 2.2 MB

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