Mutations in the haemagglutinin protein and their effect in transmission of highly pathogenic avian influenza (HPAI) H5N1 virus in sub-optimally vaccinated chickens

Ioannis Sitaras*, Xanthoula Rousou, Ben Peeters, Mart C.M. de Jong

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

Background Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field. Methods In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose. Results We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity. Discussion Our results suggest that – for the antigenic distances we investigated – vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity.

Original languageEnglish
Pages (from-to)5512-5518
JournalVaccine
Volume34
Issue number46
DOIs
Publication statusPublished - 2016

Fingerprint

H5N1 Subtype Influenza A Virus
Influenza in Birds
Hemagglutinins
avian influenza
hemagglutinins
Orthomyxoviridae
Influenza A virus
Chickens
Vaccines
vaccines
chickens
Vaccination
mutation
vaccination
Mutation
Immunity
mutants
immunity
Proteins
proteins

Keywords

  • Epidemiology
  • H5N1
  • HA
  • Influenza
  • Mutations
  • Transmission
  • Vaccination

Cite this

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title = "Mutations in the haemagglutinin protein and their effect in transmission of highly pathogenic avian influenza (HPAI) H5N1 virus in sub-optimally vaccinated chickens",
abstract = "Background Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field. Methods In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose. Results We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity. Discussion Our results suggest that – for the antigenic distances we investigated – vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity.",
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Mutations in the haemagglutinin protein and their effect in transmission of highly pathogenic avian influenza (HPAI) H5N1 virus in sub-optimally vaccinated chickens. / Sitaras, Ioannis; Rousou, Xanthoula; Peeters, Ben; de Jong, Mart C.M.

In: Vaccine, Vol. 34, No. 46, 2016, p. 5512-5518.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Mutations in the haemagglutinin protein and their effect in transmission of highly pathogenic avian influenza (HPAI) H5N1 virus in sub-optimally vaccinated chickens

AU - Sitaras, Ioannis

AU - Rousou, Xanthoula

AU - Peeters, Ben

AU - de Jong, Mart C.M.

PY - 2016

Y1 - 2016

N2 - Background Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field. Methods In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose. Results We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity. Discussion Our results suggest that – for the antigenic distances we investigated – vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity.

AB - Background Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field. Methods In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose. Results We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity. Discussion Our results suggest that – for the antigenic distances we investigated – vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity.

KW - Epidemiology

KW - H5N1

KW - HA

KW - Influenza

KW - Mutations

KW - Transmission

KW - Vaccination

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DO - 10.1016/j.vaccine.2016.10.002

M3 - Article

VL - 34

SP - 5512

EP - 5518

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 46

ER -