GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

Abstract

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.

Testing a Recombinant Form of Tetanus Toxoid as a Carrier Protein for Glycoconjugate Vaccines

“…GAC was purified, as previously described [ 35 ], from the GAS51∆M1 strain, an M protein mutant of HRO-K-51, which was kindly provided by the University of Rostock. Vi was obtained from Citrobacter NVGH 328 isolate, according to the procedure previously described [ 36 ].…”

Carriers and Antigens: New Developments in Glycoconjugate Vaccines

“…The group of Micoli et al has reported extensively on their GMMA carriers originating from different pathogens and conjugating various polysaccharide and protein antigens [ 53 , 64 ]. Palmieri et al have investigated conjugates using GMMAs originating from S. enterica and conjugating Group A Streptococcus cell wall oligosaccharide [ 65 ], whereas Scaria et al describe the application of OMV, a membrane vesicle derived from N. meningitidis as the carrier for a malaria transmission-blocking antigen.…”

Vaccine development for bacterial pathogens: Advances, challenges and prospects

“…Those factors should be considered when using this technology in vaccine design to fully exploit this technology as a platform for a multicomponent vaccine. Recently, for group A Streptococcu s, GMMA was successfully used as a carrier system for the glycoconjugate vaccine [90]. This technology resulted in a higher immune response in mice treated and immunised with GAC‐GMMA conjugate.…”