Development of a multicomponent vaccine for Streptococcus pyogenes based on the antigenic targets of IVIG
File(s)
Published version
Accepted version
Author(s)
Reglinski, M
Lynskey, NN
Choi, YJ
Sriskandan, S
Edwards, RJ
Type
Journal Article
Abstract
Objectives
Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin.
Methods
Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease.
Results
Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release.
Conclusion
Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria.
Despite over a century of research and the careful scrutiny of many promising targets, there is currently no vaccine available for the prevention of Streptococcus pyogenes infection. Through analysis of the protective, anti-streptococcal components of pooled human immunoglobulin, we previously identified ten highly conserved and invariant S. pyogenes antigens that contribute to anti-streptococcal immunity in the adult population. We sought to emulate population immunity to S. pyogenes through a process of active vaccination, using the antigens targeted by pooled human immunoglobulin.
Methods
Seven targets were produced recombinantly and mixed to form a multicomponent vaccine (Spy7). Vaccinated mice were challenged with S. pyogenes isolates representing four globally relevant serotypes (M1, M3, M12 and M89) using an established model of invasive disease.
Results
Vaccination with Spy7 stimulated the production of anti-streptococcal antibodies, and limited systemic dissemination of M1 and M3 S. pyogenes from an intramuscular infection focus. Vaccination additionally attenuated disease severity due to M1 S. pyogenes as evidenced by reduction in weight loss, and modulated cytokine release.
Conclusion
Spy7 vaccination successfully stimulated the generation of protective anti-streptococcal immunity in vivo. Identification of reactive antigens using pooled human immunoglobulin may represent a novel route to vaccine discovery for extracellular bacteria.
Date Issued
2016-02-12
Date Acceptance
2016-02-06
Citation
Journal of Infection, 2016, 72 (4), pp.450-459
ISSN
1532-2742
Publisher
Elsevier
Start Page
450
End Page
459
Journal / Book Title
Journal of Infection
Volume
72
Issue
4
Copyright Statement
© 2016 The Authors. Published by Elsevier Ltd on behalf of the The British Infection
Association. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/).
Association. This is an open access article under the CC BY license (http://
creativecommons.org/licenses/by/4.0/).
License URL
Sponsor
Wellcome Trust
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Medical Research Council (MRC)
Grant Number
087732/Z/08/Z
G0800777
RDA02 79560
MC_PC_12015
Subjects
Group A Streptococcus
IVIG
Population immunity
Streptococcus pyogenes
Vaccine
Microbiology
1103 Clinical Sciences
Publication Status
Published