Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection
Abstract Objectives The upper respiratory tract is the major entry site for Streptococcus pyogenes and influenza virus. Vaccine strategies that activate mucosal immunity could significantly reduce morbidity and mortality because of these pathogens. The severity of influenza is significantly greater...
Main Authors: | , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2021-01-01
|
Series: | Clinical & Translational Immunology |
Subjects: | |
Online Access: | https://doi.org/10.1002/cti2.1337 |
_version_ | 1818727045586223104 |
---|---|
author | Mehfuz Zaman Victor C Huber Dustin L Heiden Katerina N DeHaan Sanyogita Chandra Demi Erickson Victoria Ozberk Manisha Pandey Benjamin Bailly Gael Martin Emma L Langshaw Ali Zaid Mark vonItzstein Michael F Good |
author_facet | Mehfuz Zaman Victor C Huber Dustin L Heiden Katerina N DeHaan Sanyogita Chandra Demi Erickson Victoria Ozberk Manisha Pandey Benjamin Bailly Gael Martin Emma L Langshaw Ali Zaid Mark vonItzstein Michael F Good |
author_sort | Mehfuz Zaman |
collection | DOAJ |
description | Abstract Objectives The upper respiratory tract is the major entry site for Streptococcus pyogenes and influenza virus. Vaccine strategies that activate mucosal immunity could significantly reduce morbidity and mortality because of these pathogens. The severity of influenza is significantly greater if a streptococcal infection occurs during the viraemic period and generally viral infections complicated by a subsequent bacterial infection are known as super‐infections. We describe an innovative vaccine strategy against influenza virus:S. pyogenes super‐infection. Moreover, we provide the first description of a liposomal multi‐pathogen‐based platform that enables the incorporation of both viral and bacterial antigens into a vaccine and constitutes a transformative development. Methods Specifically, we have explored a vaccination strategy with biocompatible liposomes that express conserved streptococcal and influenza A virus B‐cell epitopes on their surface and contain encapsulated diphtheria toxoid as a source of T‐cell help. The vaccine is adjuvanted by inclusion of the synthetic analogue of monophosphoryl lipid A, 3D‐PHAD. Results We observe that this vaccine construct induces an Immunoglobulin A (IgA) response in both mice and ferrets. Vaccination reduces viral load in ferrets from influenza challenge and protects mice from both pathogens. Notably, vaccination significantly reduces both mortality and morbidity associated with a super‐infection. Conclusion The vaccine design is modular and could be adapted to include B‐cell epitopes from other mucosal pathogens where an IgA response is required for protection. |
first_indexed | 2024-12-17T22:07:51Z |
format | Article |
id | doaj.art-74e432a6e1574a4db2f011bf4476c694 |
institution | Directory Open Access Journal |
issn | 2050-0068 |
language | English |
last_indexed | 2024-12-17T22:07:51Z |
publishDate | 2021-01-01 |
publisher | Wiley |
record_format | Article |
series | Clinical & Translational Immunology |
spelling | doaj.art-74e432a6e1574a4db2f011bf4476c6942022-12-21T21:30:49ZengWileyClinical & Translational Immunology2050-00682021-01-01109n/an/a10.1002/cti2.1337Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infectionMehfuz Zaman0Victor C Huber1Dustin L Heiden2Katerina N DeHaan3Sanyogita Chandra4Demi Erickson5Victoria Ozberk6Manisha Pandey7Benjamin Bailly8Gael Martin9Emma L Langshaw10Ali Zaid11Mark vonItzstein12Michael F Good13Institute for Glycomics Griffith University Gold Coast QLD AustraliaDivision of Basic Biomedical Sciences Sanford School of Medicine University of South Dakota Vermillion SD USADivision of Basic Biomedical Sciences Sanford School of Medicine University of South Dakota Vermillion SD USADivision of Basic Biomedical Sciences Sanford School of Medicine University of South Dakota Vermillion SD USADivision of Basic Biomedical Sciences Sanford School of Medicine University of South Dakota Vermillion SD USADivision of Basic Biomedical Sciences Sanford School of Medicine University of South Dakota Vermillion SD USAInstitute for Glycomics Griffith University Gold Coast QLD AustraliaInstitute for Glycomics Griffith University Gold Coast QLD AustraliaInstitute for Glycomics Griffith University Gold Coast QLD AustraliaInstitute for Glycomics Griffith University Gold Coast QLD AustraliaInstitute for Glycomics Griffith University Gold Coast QLD AustraliaThe Emerging Viruses, Inflammation and Therapeutics Group Menzies Health Institute Queensland Griffith University Gold Coast QLD AustraliaInstitute for Glycomics Griffith University Gold Coast QLD AustraliaInstitute for Glycomics Griffith University Gold Coast QLD AustraliaAbstract Objectives The upper respiratory tract is the major entry site for Streptococcus pyogenes and influenza virus. Vaccine strategies that activate mucosal immunity could significantly reduce morbidity and mortality because of these pathogens. The severity of influenza is significantly greater if a streptococcal infection occurs during the viraemic period and generally viral infections complicated by a subsequent bacterial infection are known as super‐infections. We describe an innovative vaccine strategy against influenza virus:S. pyogenes super‐infection. Moreover, we provide the first description of a liposomal multi‐pathogen‐based platform that enables the incorporation of both viral and bacterial antigens into a vaccine and constitutes a transformative development. Methods Specifically, we have explored a vaccination strategy with biocompatible liposomes that express conserved streptococcal and influenza A virus B‐cell epitopes on their surface and contain encapsulated diphtheria toxoid as a source of T‐cell help. The vaccine is adjuvanted by inclusion of the synthetic analogue of monophosphoryl lipid A, 3D‐PHAD. Results We observe that this vaccine construct induces an Immunoglobulin A (IgA) response in both mice and ferrets. Vaccination reduces viral load in ferrets from influenza challenge and protects mice from both pathogens. Notably, vaccination significantly reduces both mortality and morbidity associated with a super‐infection. Conclusion The vaccine design is modular and could be adapted to include B‐cell epitopes from other mucosal pathogens where an IgA response is required for protection.https://doi.org/10.1002/cti2.1337liposomesmodular vaccinemucosal vaccinesmulti‐pathogensuper‐infections |
spellingShingle | Mehfuz Zaman Victor C Huber Dustin L Heiden Katerina N DeHaan Sanyogita Chandra Demi Erickson Victoria Ozberk Manisha Pandey Benjamin Bailly Gael Martin Emma L Langshaw Ali Zaid Mark vonItzstein Michael F Good Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection Clinical & Translational Immunology liposomes modular vaccine mucosal vaccines multi‐pathogen super‐infections |
title | Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection |
title_full | Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection |
title_fullStr | Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection |
title_full_unstemmed | Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection |
title_short | Combinatorial liposomal peptide vaccine induces IgA and confers protection against influenza virus and bacterial super‐infection |
title_sort | combinatorial liposomal peptide vaccine induces iga and confers protection against influenza virus and bacterial super infection |
topic | liposomes modular vaccine mucosal vaccines multi‐pathogen super‐infections |
url | https://doi.org/10.1002/cti2.1337 |
work_keys_str_mv | AT mehfuzzaman combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT victorchuber combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT dustinlheiden combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT katerinandehaan combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT sanyogitachandra combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT demierickson combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT victoriaozberk combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT manishapandey combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT benjaminbailly combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT gaelmartin combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT emmallangshaw combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT alizaid combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT markvonitzstein combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection AT michaelfgood combinatorialliposomalpeptidevaccineinducesigaandconfersprotectionagainstinfluenzavirusandbacterialsuperinfection |