GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>

Group A <i>Streptococcus</i> (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we ex...

Full description

Bibliographic Details
Main Authors: Elena Palmieri, Zoltán Kis, James Ozanne, Roberta Di Benedetto, Beatrice Ricchetti, Luisa Massai, Martina Carducci, Davide Oldrini, Gianmarco Gasperini, Maria Grazia Aruta, Omar Rossi, Cleo Kontoravdi, Nilay Shah, Fatme Mawas, Francesca Micoli
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:Vaccines
Subjects:
Online Access:https://www.mdpi.com/2076-393X/10/7/1034
_version_ 1827603673426952192
author Elena Palmieri
Zoltán Kis
James Ozanne
Roberta Di Benedetto
Beatrice Ricchetti
Luisa Massai
Martina Carducci
Davide Oldrini
Gianmarco Gasperini
Maria Grazia Aruta
Omar Rossi
Cleo Kontoravdi
Nilay Shah
Fatme Mawas
Francesca Micoli
author_facet Elena Palmieri
Zoltán Kis
James Ozanne
Roberta Di Benedetto
Beatrice Ricchetti
Luisa Massai
Martina Carducci
Davide Oldrini
Gianmarco Gasperini
Maria Grazia Aruta
Omar Rossi
Cleo Kontoravdi
Nilay Shah
Fatme Mawas
Francesca Micoli
author_sort Elena Palmieri
collection DOAJ
description Group A <i>Streptococcus</i> (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties. Immunogenicity of GAC-GMMA conjugate was evaluated in different animal species in comparison to GAC-CRM<sub>197</sub>; and the two conjugates were also compared from a techno-economic point of view. GMMA proved to be a good alternative carrier for GAC, resulting in a higher immune response compared to CRM<sub>197</sub> in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM<sub>197</sub>, GMMA induced significant levels of anti-GAC IgG titers in mice also in the absence of Alhydrogel. In rabbits, a difference in the immune response could not be appreciated; however, antibodies from GAC-GMMA-immunized animals showed higher affinity toward purified GAC antigen compared to those elicited by GAC-CRM<sub>197</sub>. In addition, the GAC-GMMA production process proved to be more cost-effective, making this conjugate particularly attractive for low- and middle-income countries, where this pathogen has a huge burden.
first_indexed 2024-03-09T05:44:01Z
format Article
id doaj.art-51ad062515b741b4afe2d444e2ee2b4a
institution Directory Open Access Journal
issn 2076-393X
language English
last_indexed 2024-03-09T05:44:01Z
publishDate 2022-06-01
publisher MDPI AG
record_format Article
series Vaccines
spelling doaj.art-51ad062515b741b4afe2d444e2ee2b4a2023-12-03T12:22:15ZengMDPI AGVaccines2076-393X2022-06-01107103410.3390/vaccines10071034GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>Elena Palmieri0Zoltán Kis1James Ozanne2Roberta Di Benedetto3Beatrice Ricchetti4Luisa Massai5Martina Carducci6Davide Oldrini7Gianmarco Gasperini8Maria Grazia Aruta9Omar Rossi10Cleo Kontoravdi11Nilay Shah12Fatme Mawas13Francesca Micoli14GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyThe Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UKThe National Institute for Biological Standards and Control (NIBSC), South Mimms EN6 3QG, UKGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyThe Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UKThe Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UKThe National Institute for Biological Standards and Control (NIBSC), South Mimms EN6 3QG, UKGSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, ItalyGroup A <i>Streptococcus</i> (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties. Immunogenicity of GAC-GMMA conjugate was evaluated in different animal species in comparison to GAC-CRM<sub>197</sub>; and the two conjugates were also compared from a techno-economic point of view. GMMA proved to be a good alternative carrier for GAC, resulting in a higher immune response compared to CRM<sub>197</sub> in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM<sub>197</sub>, GMMA induced significant levels of anti-GAC IgG titers in mice also in the absence of Alhydrogel. In rabbits, a difference in the immune response could not be appreciated; however, antibodies from GAC-GMMA-immunized animals showed higher affinity toward purified GAC antigen compared to those elicited by GAC-CRM<sub>197</sub>. In addition, the GAC-GMMA production process proved to be more cost-effective, making this conjugate particularly attractive for low- and middle-income countries, where this pathogen has a huge burden.https://www.mdpi.com/2076-393X/10/7/1034Group A <i>Streptococcus</i>GMMAglycoconjugateGroup A Carbohydrate
spellingShingle Elena Palmieri
Zoltán Kis
James Ozanne
Roberta Di Benedetto
Beatrice Ricchetti
Luisa Massai
Martina Carducci
Davide Oldrini
Gianmarco Gasperini
Maria Grazia Aruta
Omar Rossi
Cleo Kontoravdi
Nilay Shah
Fatme Mawas
Francesca Micoli
GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>
Vaccines
Group A <i>Streptococcus</i>
GMMA
glycoconjugate
Group A Carbohydrate
title GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>
title_full GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>
title_fullStr GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>
title_full_unstemmed GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>
title_short GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>
title_sort gmma as an alternative carrier for a glycoconjugate vaccine against group a i streptococcus i
topic Group A <i>Streptococcus</i>
GMMA
glycoconjugate
Group A Carbohydrate
url https://www.mdpi.com/2076-393X/10/7/1034
work_keys_str_mv AT elenapalmieri gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT zoltankis gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT jamesozanne gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT robertadibenedetto gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT beatricericchetti gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT luisamassai gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT martinacarducci gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT davideoldrini gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT gianmarcogasperini gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT mariagraziaaruta gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT omarrossi gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT cleokontoravdi gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT nilayshah gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT fatmemawas gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi
AT francescamicoli gmmaasanalternativecarrierforaglycoconjugatevaccineagainstgroupaistreptococcusi