Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies

ABSTRACT Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. H...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Tania Rivera-Hernandez, Mira Syahira Rhyme, Amanda J. Cork, Scott Jones, Celia Segui-Perez, Livia Brunner, Johanna Richter, Nikolai Petrovsky, Maria Lawrenz, David Goldblatt, Nicolas Collin, Mark J. Walker
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	group A Streptococcus vaccines adjuvants invasive disease Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a45d19c21a7d4f59b307fc52028682b2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a45d19c21a7d4f59b307fc52028682b2
record_format	dspace
spelling	oai:doaj.org-article:a45d19c21a7d4f59b307fc52028682b22021-11-15T15:57:02ZVaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies10.1128/mBio.00122-202150-7511https://doaj.org/article/a45d19c21a7d4f59b307fc52028682b22020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00122-20https://doaj.org/toc/2150-7511ABSTRACT Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-γ), and tumor necrosis alpha (TNF-α) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy. IMPORTANCE Availability of a group A Streptococcus vaccine remains an unmet public health need. Here, we tested different adjuvant formulations to improve the protective efficacy of non-M protein vaccine Combo5 in an invasive disease model. We show that novel adjuvants can dramatically shape the type of immune response developed following immunization with Combo5 and significantly improve protection. In addition, protection afforded by Combo5 is not mediated by opsonizing antibodies, believed to be the main correlate of protection against GAS infections. Overall, this report highlights the importance of adjuvant selection in raising protective immune responses against GAS invasive infection. Adjuvants that can provide a more balanced Th1/Th2-type response may be required to optimize protection of GAS vaccines, particularly those based on non-M protein antigens.Tania Rivera-HernandezMira Syahira RhymeAmanda J. CorkScott JonesCelia Segui-PerezLivia BrunnerJohanna RichterNikolai PetrovskyMaria LawrenzDavid GoldblattNicolas CollinMark J. WalkerAmerican Society for Microbiologyarticlegroup A Streptococcusvaccinesadjuvantsinvasive diseaseMicrobiologyQR1-502ENmBio, Vol 11, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	group A Streptococcus vaccines adjuvants invasive disease Microbiology QR1-502
spellingShingle	group A Streptococcus vaccines adjuvants invasive disease Microbiology QR1-502 Tania Rivera-Hernandez Mira Syahira Rhyme Amanda J. Cork Scott Jones Celia Segui-Perez Livia Brunner Johanna Richter Nikolai Petrovsky Maria Lawrenz David Goldblatt Nicolas Collin Mark J. Walker Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies
description	ABSTRACT Recent global advocacy efforts have highlighted the importance of development of a vaccine against group A Streptococcus (GAS). Combo5 is a non-M protein-based vaccine that provides protection against GAS skin infection in mice and reduces the severity of pharyngitis in nonhuman primates. However, Combo5 with the addition of aluminum hydroxide (alum) as an adjuvant failed to protect against invasive GAS infection of mice. Here, we show that formulation of Combo5 with adjuvants containing saponin QS21 significantly improves protective efficacy, even though all 7 adjuvants tested generated high antigen-specific IgG antibody titers, including alum. Detailed characterization of Combo5 formulated with SMQ adjuvant, a squalene-in-water emulsion containing a TLR4 agonist and QS21, showed significant differences from the results obtained with alum in IgG subclasses generated following immunization, with an absence of GAS opsonizing antibodies. SMQ, but not alum, generated strong interleukin-6 (IL-6), gamma interferon (IFN-γ), and tumor necrosis alpha (TNF-α) responses. This work highlights the importance of adjuvant selection for non-M protein-based GAS vaccines to optimize immune responses and protective efficacy. IMPORTANCE Availability of a group A Streptococcus vaccine remains an unmet public health need. Here, we tested different adjuvant formulations to improve the protective efficacy of non-M protein vaccine Combo5 in an invasive disease model. We show that novel adjuvants can dramatically shape the type of immune response developed following immunization with Combo5 and significantly improve protection. In addition, protection afforded by Combo5 is not mediated by opsonizing antibodies, believed to be the main correlate of protection against GAS infections. Overall, this report highlights the importance of adjuvant selection in raising protective immune responses against GAS invasive infection. Adjuvants that can provide a more balanced Th1/Th2-type response may be required to optimize protection of GAS vaccines, particularly those based on non-M protein antigens.
format	article
author	Tania Rivera-Hernandez Mira Syahira Rhyme Amanda J. Cork Scott Jones Celia Segui-Perez Livia Brunner Johanna Richter Nikolai Petrovsky Maria Lawrenz David Goldblatt Nicolas Collin Mark J. Walker
author_facet	Tania Rivera-Hernandez Mira Syahira Rhyme Amanda J. Cork Scott Jones Celia Segui-Perez Livia Brunner Johanna Richter Nikolai Petrovsky Maria Lawrenz David Goldblatt Nicolas Collin Mark J. Walker
author_sort	Tania Rivera-Hernandez
title	Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies
title_short	Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies
title_full	Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies
title_fullStr	Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies
title_full_unstemmed	Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies
title_sort	vaccine-induced th1-type response protects against invasive group a <italic toggle="yes">streptococcus</italic> infection in the absence of opsonizing antibodies
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/a45d19c21a7d4f59b307fc52028682b2
work_keys_str_mv	AT taniariverahernandez vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT mirasyahirarhyme vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT amandajcork vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT scottjones vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT celiaseguiperez vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT liviabrunner vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT johannarichter vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT nikolaipetrovsky vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT marialawrenz vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT davidgoldblatt vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT nicolascollin vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies AT markjwalker vaccineinducedth1typeresponseprotectsagainstinvasivegroupaitalictoggleyesstreptococcusitalicinfectionintheabsenceofopsonizingantibodies
_version_	1718427043297755136

Vaccine-Induced Th1-Type Response Protects against Invasive Group A <italic toggle="yes">Streptococcus</italic> Infection in the Absence of Opsonizing Antibodies

Ejemplares similares