Evidence for positive selection of hepatitis A virus antigenic variants in vaccinated men-having-sex-with men patients: Implications for immunization policies.
Adult
Capsid Proteins
/ genetics
Disease Outbreaks
Europe
/ epidemiology
Evolution, Molecular
Hepatitis A
/ epidemiology
Hepatitis A Antigens
/ genetics
Hepatitis A virus
/ genetics
High-Throughput Nucleotide Sequencing
/ methods
Homosexuality, Male
Humans
Male
Middle Aged
Mutation
Quasispecies
Sequence Analysis, RNA
/ methods
Vaccination
Deep-sequencing
MSM
Quasispecies
Vaccine escape-mutants
Journal
EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039
Informations de publication
Date de publication:
Jan 2019
Jan 2019
Historique:
received:
08
08
2018
revised:
13
11
2018
accepted:
13
11
2018
pubmed:
26
11
2018
medline:
14
6
2019
entrez:
26
11
2018
Statut:
ppublish
Résumé
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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
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.
FINDINGS
RESULTS
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.
INTERPRETATION
CONCLUSIONS
Our data suggest positive selection of antigenic variants in some vaccinated patients, raising concerns for new vaccination polices directed to the MSM group.
Identifiants
pubmed: 30472089
pii: S2352-3964(18)30516-4
doi: 10.1016/j.ebiom.2018.11.023
pmc: PMC6354442
pii:
doi:
Substances chimiques
Capsid Proteins
0
Hepatitis A Antigens
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
348-357Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018. Published by Elsevier B.V.
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