Proof of concept for a single-dose Group B Streptococcus vaccine based on capsular polysaccharide conjugated to Qβ virus-like particles

Abstract

A maternal vaccine to protect neonates against Group B Streptococcus invasive infection is an unmet medical need. Such a vaccine should ideally be offered during the third trimester of pregnancy and induce strong immune responses after a single dose to maximize the time for placental transfer of protective antibodies. A key target antigen is the capsular polysaccharide, an anti-phagocytic virulence factor that elicits protective antibodies when conjugated to carrier proteins. The most prevalent polysaccharide serotypes conjugated to tetanus or diphtheria toxoids have been tested in humans as monovalent and multivalent formulations, showing excellent safety profiles and immunogenicity. However, responses were suboptimal in unprimed individuals after a single shot, the ideal schedule for vaccination during the third trimester of pregnancy. In the present study, we obtained and optimized self-assembling virus-like particles conjugated to Group B Streptococcus capsular polysaccharides. The resulting glyco-nanoparticles elicited strong immune responses in mice already after one immunization, providing pre-clinical proof of concept for a single-dose vaccine.

Vaccines for Streptococcus agalactiae: current status and future perspectives

“…Furthermore, IgG and opsonophagocytic activity induced by the CPSII-Qb conjugate reached a maximum at day 42 and persisted until day 134. Similar data were observed using Qb carriers with capsular polysaccharide Ia, suggesting that the same approach could be applicable and tested for the other capsule types (19).…”

“…NPs and VLPs are systems that improve the uptake and activation of immune cells due to their size and dense antigen display ( 18 ). In 2023, Carboni and colleagues obtained and optimized self-assembling virus-like particles conjugated to S. agalactiae CPS-II, resulting in a glyco-nanoparticles elicited strong immune responses in mice already after one immunization, providing pre-clinical proof of concept for a single-dose vaccine ( 19 ).…”

Impact of Protein Nanoparticle Shape on the Immunogenicity of Antimicrobial Glycoconjugate Vaccines

“…In addition to their use as antigens, protein nanoparticles can also serve as carriers, addressing key challenges in vaccine design. They can carry various biomolecules, including polysaccharides [24,25], viral [26][27][28][29] and bacterial [30][31][32][33] protein antigens, peptides [34][35][36] and glycopeptides [37], nucleic acids [38] and small molecules [39,40] making them versatile platforms for vaccine development. Protein-based nanocarriers have displayed great potential for coronavirus vaccine research [41][42][43], indicating their relevance in addressing current global health challenges.…”

“…Despite the licensing of various VLP-based vaccines and continuous progress in conjugation techniques for bacterial saccharide antigens, few glycoconjugated nanoparticles are currently under development in the pre-clinical stage. Carrier protein nanoparticles have been employed to promote a strong T-cell and long-lasting anti-glycan immune response against N. meningitidis, K. pneumoniae, and V. cholerae [44][45][46], to induce nanomolar affinity of antibodies towards pneumococcal saccharide antigens [45,47] or to develop a single-dose vaccine addressing the medical need for a maternal vaccine against Group B Streptococcus (GBS) [25]. Additionally, in recent years, Nano-B5 nanoparticles based on the bacterial pentameric AB-5 toxin and designed through computational methods have been successfully bioconjugated to the O-polysaccharides of Klebsiella pneumoniae and Shigella flexneri with promising prophylactic effects in mice, proving to be a potential technology for the development of AMR vaccines [48].…”