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Using Surface Immunogenic Protein as a Carrier Protein to Elicit Protective Antibody to Multiple Serotypes for
Huiqi Duan1,2, Wenhua Huang2, Qingyu Lv2
1School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
Insights
Group B Streptococcus (GBS) vaccines using the Surface immunogenic protein (Sip) show promise. Ia-Sip conjugates induced high antibody titers and provided broad protection against GBS, outperforming traditional carriers.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Group B Streptococcus (GBS) is a major cause of life-threatening infections in vulnerable populations.
- Maternal vaccination is a key strategy to prevent GBS transmission from mother to infant.
- Current GBS vaccines often use carrier proteins like CRM197, but novel approaches are being explored.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of a novel GBS vaccine candidate using the Surface immunogenic protein (Sip) as a carrier.
- To compare the performance of a type Ia capsular polysaccharide (CPS) conjugated to Sip against a traditional CRM197 carrier.
- To assess the potential of Sip as a serotype-independent carrier for GBS vaccines.
Main Methods:
- Conjugation of GBS type Ia CPS to Sip and CRM197 carrier proteins.
- Immunization of rabbits and mice with the candidate vaccines.
- Analysis of antibody titers, opsonophagocytosis, and passive immune protection.
- In vivo challenge studies in mice to assess protection against lethal GBS infection.
Main Results:
- The Ia-Sip conjugate vaccine elicited antibody titers comparable to the Ia-CRM197 vaccine and significantly higher than the unconjugated polysaccharide.
- Both Ia-Sip and Ia-CRM197 vaccines demonstrated superior opsonophagocytic activity and passive protection compared to the Ia polysaccharide alone.
- Serum from the Ia-Sip group exhibited cross-protection against multiple GBS serotypes in vitro and in vivo.
- Complete protection against lethal GBS challenge was observed in mice immunized with the Ia-Sip vaccine, including protection against type III strains.
Conclusions:
- The Surface immunogenic protein (Sip) is a potent carrier for GBS capsular polysaccharide conjugate vaccines.
- Ia-Sip conjugates are immunogenic and provide serotype-independent protection against GBS.
- Sip represents a promising alternative carrier protein for developing broadly protective GBS vaccines.
Abstract:
Group B Streptococcus (GBS) is a life-threatening opportunistic pathogen, particularly in pregnant women, infants, and the elderly. Currently, maternal vaccination is considered the most viable long-term option for preventing GBS mother-to-infant infection, and two polysaccharide conjugate vaccines utilizing CRM197 as a carrier protein have undergone clinical phase II trials. Surface immunogenic protein (Sip), present in all identified serotypes of GBS strains so far, is a protective surface protein of GBS. In this study, the type Ia capsular polysaccharide (CPS) of GBS was utilized as a model to develop candidate antigens for a polysaccharide conjugate vaccine by coupling it with the Sip of GBS and the traditional carrier protein CRM197. Serum analysis from immunized New Zealand rabbits and CD1 mice revealed that there was no significant difference in antibody titers between the Ia-Sip group and Ia-CRM197 group; however, both were significantly higher than those observed in the Ia polysaccharide group. Opsonophagocytosis and passive immune protection results using rabbit serum indicated no significant difference between the Ia-Sip and Ia-CRM197 groups, both outperforming the Ia polysaccharide group. Furthermore, serum from the Ia-Sip group had a cross-protective effect on multiple types of GBS strains. The challenge test results in CD1 mice demonstrated that the Ia-Sip group provided complete protection against lethal doses of bacteria and also showed cross-protection against type III strain. Our study demonstrates for the first time that Ia-Sip is immunogenic and provides serotype-independent protection in glycan conjugate vaccines, which also indicates Sip may serve as an excellent carrier protein for GBS glycan conjugate vaccines and provide cross-protection against multiple GBS strains.
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