Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions

Influenza A virus presents a constant pandemic threat due to the mutagenic nature of the virus and the inadequacy of current vaccines to protect against emerging strains. We have developed a whole-inactivated influenza vaccine using γ-irradiation (γ-Flu) that can protect against both vaccine-include...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Eve Victoria Singleton, Chloe Jayne Gates, Shannon Christa David, Timothy Raymond Hirst, Justin Bryan Davies, Mohammed Alsharifi
Formato: article
Lenguaje:EN
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://doaj.org/article/7976515b8a6744d6af5fc1635d09c44f
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:7976515b8a6744d6af5fc1635d09c44f
record_format dspace
spelling oai:doaj.org-article:7976515b8a6744d6af5fc1635d09c44f2021-11-30T18:43:37ZEnhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions1664-322410.3389/fimmu.2021.761632https://doaj.org/article/7976515b8a6744d6af5fc1635d09c44f2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.761632/fullhttps://doaj.org/toc/1664-3224Influenza A virus presents a constant pandemic threat due to the mutagenic nature of the virus and the inadequacy of current vaccines to protect against emerging strains. We have developed a whole-inactivated influenza vaccine using γ-irradiation (γ-Flu) that can protect against both vaccine-included strains as well as emerging pandemic strains. γ-irradiation is a widely used inactivation method and several γ-irradiated vaccines are currently in clinical or pre-clinical testing. To enhance vaccine efficacy, irradiation conditions should be carefully considered, particularly irradiation temperature. Specifically, while more damage to virus structure is expected when using higher irradiation temperatures, reduced radiation doses will be required to achieve sterility. In this study, we compared immunogenicity of γ-Flu irradiated at room temperature, chilled on ice or frozen on dry ice using different doses of γ-irradiation to meet internationally accepted sterility assurance levels. We found that, when irradiating at sterilising doses, the structural integrity and vaccine efficacy were well maintained in all preparations regardless of irradiation temperature. In fact, using a higher temperature and lower radiation dose appeared to induce higher neutralising antibody responses and more effective cytotoxic T cell responses. This outcome is expected to simplify irradiation protocols for manufacturing of highly effective irradiated vaccines.Eve Victoria SingletonChloe Jayne GatesShannon Christa DavidTimothy Raymond HirstTimothy Raymond HirstJustin Bryan DaviesMohammed AlsharifiMohammed AlsharifiFrontiers Media S.A.articleinfluenza A virusgamma radiationvaccinesterility assurance level (SAL)irradiation conditionsuniversal influenza A vaccineImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution DOAJ
collection DOAJ
language EN
topic influenza A virus
gamma radiation
vaccine
sterility assurance level (SAL)
irradiation conditions
universal influenza A vaccine
Immunologic diseases. Allergy
RC581-607
spellingShingle influenza A virus
gamma radiation
vaccine
sterility assurance level (SAL)
irradiation conditions
universal influenza A vaccine
Immunologic diseases. Allergy
RC581-607
Eve Victoria Singleton
Chloe Jayne Gates
Shannon Christa David
Timothy Raymond Hirst
Timothy Raymond Hirst
Justin Bryan Davies
Mohammed Alsharifi
Mohammed Alsharifi
Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions
description Influenza A virus presents a constant pandemic threat due to the mutagenic nature of the virus and the inadequacy of current vaccines to protect against emerging strains. We have developed a whole-inactivated influenza vaccine using γ-irradiation (γ-Flu) that can protect against both vaccine-included strains as well as emerging pandemic strains. γ-irradiation is a widely used inactivation method and several γ-irradiated vaccines are currently in clinical or pre-clinical testing. To enhance vaccine efficacy, irradiation conditions should be carefully considered, particularly irradiation temperature. Specifically, while more damage to virus structure is expected when using higher irradiation temperatures, reduced radiation doses will be required to achieve sterility. In this study, we compared immunogenicity of γ-Flu irradiated at room temperature, chilled on ice or frozen on dry ice using different doses of γ-irradiation to meet internationally accepted sterility assurance levels. We found that, when irradiating at sterilising doses, the structural integrity and vaccine efficacy were well maintained in all preparations regardless of irradiation temperature. In fact, using a higher temperature and lower radiation dose appeared to induce higher neutralising antibody responses and more effective cytotoxic T cell responses. This outcome is expected to simplify irradiation protocols for manufacturing of highly effective irradiated vaccines.
format article
author Eve Victoria Singleton
Chloe Jayne Gates
Shannon Christa David
Timothy Raymond Hirst
Timothy Raymond Hirst
Justin Bryan Davies
Mohammed Alsharifi
Mohammed Alsharifi
author_facet Eve Victoria Singleton
Chloe Jayne Gates
Shannon Christa David
Timothy Raymond Hirst
Timothy Raymond Hirst
Justin Bryan Davies
Mohammed Alsharifi
Mohammed Alsharifi
author_sort Eve Victoria Singleton
title Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions
title_short Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions
title_full Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions
title_fullStr Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions
title_full_unstemmed Enhanced Immunogenicity of a Whole-Inactivated Influenza A Virus Vaccine Using Optimised Irradiation Conditions
title_sort enhanced immunogenicity of a whole-inactivated influenza a virus vaccine using optimised irradiation conditions
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/7976515b8a6744d6af5fc1635d09c44f
work_keys_str_mv AT evevictoriasingleton enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
AT chloejaynegates enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
AT shannonchristadavid enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
AT timothyraymondhirst enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
AT timothyraymondhirst enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
AT justinbryandavies enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
AT mohammedalsharifi enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
AT mohammedalsharifi enhancedimmunogenicityofawholeinactivatedinfluenzaavirusvaccineusingoptimisedirradiationconditions
_version_ 1718406333082894336