GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A <i>Streptococcus</i>
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
Affiliations
Elena Palmieri
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Zoltán Kis
The Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
James Ozanne
The National Institute for Biological Standards and Control (NIBSC), South Mimms EN6 3QG, UK
Roberta Di Benedetto
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Beatrice Ricchetti
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Luisa Massai
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Martina Carducci
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Davide Oldrini
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Gianmarco Gasperini
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Maria Grazia Aruta
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Omar Rossi
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Cleo Kontoravdi
The Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Nilay Shah
The Sargent Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
Fatme Mawas
The National Institute for Biological Standards and Control (NIBSC), South Mimms EN6 3QG, UK
Francesca Micoli
GSK Vaccines Institute for Global Health (GVGH), Via Fiorentina 1, 53100 Siena, Italy
Group A Streptococcus (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-CRM197; 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 CRM197 in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM197, 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-CRM197. 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.
