Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy

Influenza viruses affect millions of people worldwide on an annual basis. Although vaccines are available, influenza still causes significant human mortality and morbidity. Vaccines target the major influenza surface glycoprotein hemagglutinin (HA). However, circulating HA subtypes undergo continual...

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Main Authors: John R. Gallagher, Dustin M. McCraw, Udana Torian, Neetu M. Gulati, Mallory L. Myers, Michael T. Conlon, Audray K. Harris
Format: Article
Language:English
Published: MDPI AG 2018-05-01
Series:Vaccines
Subjects:
Online Access:http://www.mdpi.com/2076-393X/6/2/31
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author John R. Gallagher
Dustin M. McCraw
Udana Torian
Neetu M. Gulati
Mallory L. Myers
Michael T. Conlon
Audray K. Harris
author_facet John R. Gallagher
Dustin M. McCraw
Udana Torian
Neetu M. Gulati
Mallory L. Myers
Michael T. Conlon
Audray K. Harris
author_sort John R. Gallagher
collection DOAJ
description Influenza viruses affect millions of people worldwide on an annual basis. Although vaccines are available, influenza still causes significant human mortality and morbidity. Vaccines target the major influenza surface glycoprotein hemagglutinin (HA). However, circulating HA subtypes undergo continual variation in their dominant epitopes, requiring vaccines to be updated annually. A goal of next-generation influenza vaccine research is to produce broader protective immunity against the different types, subtypes, and strains of influenza viruses. One emerging strategy is to focus the immune response away from variable epitopes, and instead target the conserved stem region of HA. To increase the display and immunogenicity of the HA stem, nanoparticles are being developed to display epitopes in a controlled spatial arrangement to improve immunogenicity and elicit protective immune responses. Engineering of these nanoparticles requires structure-guided design to optimize the fidelity and valency of antigen presentation. Here, we review electron microscopy applied to study the 3D structures of influenza viruses and different vaccine antigens. Structure-guided information from electron microscopy should be integrated into pipelines for the development of both more efficacious seasonal and universal influenza vaccine antigens. The lessons learned from influenza vaccine electron microscopic research could aid in the development of novel vaccines for other pathogens.
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spelling doaj.art-b2da208d3d264c15b8467b66aa2365de2022-12-22T04:00:46ZengMDPI AGVaccines2076-393X2018-05-01623110.3390/vaccines6020031vaccines6020031Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron MicroscopyJohn R. Gallagher0Dustin M. McCraw1Udana Torian2Neetu M. Gulati3Mallory L. Myers4Michael T. Conlon5Audray K. Harris6Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6351, Bethesda, MD 20892, USALaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6351, Bethesda, MD 20892, USALaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6351, Bethesda, MD 20892, USALaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6351, Bethesda, MD 20892, USALaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6351, Bethesda, MD 20892, USALaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6351, Bethesda, MD 20892, USALaboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 50 South Drive, Room 6351, Bethesda, MD 20892, USAInfluenza viruses affect millions of people worldwide on an annual basis. Although vaccines are available, influenza still causes significant human mortality and morbidity. Vaccines target the major influenza surface glycoprotein hemagglutinin (HA). However, circulating HA subtypes undergo continual variation in their dominant epitopes, requiring vaccines to be updated annually. A goal of next-generation influenza vaccine research is to produce broader protective immunity against the different types, subtypes, and strains of influenza viruses. One emerging strategy is to focus the immune response away from variable epitopes, and instead target the conserved stem region of HA. To increase the display and immunogenicity of the HA stem, nanoparticles are being developed to display epitopes in a controlled spatial arrangement to improve immunogenicity and elicit protective immune responses. Engineering of these nanoparticles requires structure-guided design to optimize the fidelity and valency of antigen presentation. Here, we review electron microscopy applied to study the 3D structures of influenza viruses and different vaccine antigens. Structure-guided information from electron microscopy should be integrated into pipelines for the development of both more efficacious seasonal and universal influenza vaccine antigens. The lessons learned from influenza vaccine electron microscopic research could aid in the development of novel vaccines for other pathogens.http://www.mdpi.com/2076-393X/6/2/31influenzavaccinesstructureelectron microscopycryo-EMdesign
spellingShingle John R. Gallagher
Dustin M. McCraw
Udana Torian
Neetu M. Gulati
Mallory L. Myers
Michael T. Conlon
Audray K. Harris
Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy
Vaccines
influenza
vaccines
structure
electron microscopy
cryo-EM
design
title Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy
title_full Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy
title_fullStr Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy
title_full_unstemmed Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy
title_short Characterization of Hemagglutinin Antigens on Influenza Virus and within Vaccines Using Electron Microscopy
title_sort characterization of hemagglutinin antigens on influenza virus and within vaccines using electron microscopy
topic influenza
vaccines
structure
electron microscopy
cryo-EM
design
url http://www.mdpi.com/2076-393X/6/2/31
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