Development of a bivalent conjugate vaccine candidate against rotaviral diarrhea and tuberculosis using polysaccharide from Mycobacterium tuberculosis conjugated to ΔVP8 protein from rotavirus

• Published in: Vaccine Vol. 39; no. 45; pp. 6644 - 6652
• Main Authors: Park, Wook-Jin, Yoon, Yeon-Kyung, Kim, Youngmi, Park, Ji-Sun, Pansuriya, Ruchirkumar, Cho, Sang-Nae, Seok, Yeong-Jae, Ganapathy, Ravi
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 29.10.2021; Elsevier Limited
• Subjects: Antibodies; Antigens; Capsular polysaccharides; Carbohydrates; Carrier protein; Chromatography; Conjugate vaccine; Conjugates; Conjugation; Current carriers; Diarrhea; Diphtheria; E coli; Epitopes; Glycoconjugates; Immune response; Immune system; Immunization; Immunogenicity; Lymphocytes; Lymphocytes T; Molecular weight; Monoclonal antibodies; Mycobacterium tuberculosis; Pathogens; Pediatrics; Polysaccharides; Protective antigen; Protein D; Proteins; Rotavirus; Sodium; Spike protein; Tuberculosis; Vaccines; Viruses; ΔVP8; United States > US; Germany; Tuberculosis; ΔVP8; Rotavirus; Conjugate vaccine; Carrier protein
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2021.09.067

Conjugation of carbohydrate antigens with a carrier protein is a clinically proven strategy to overcome the poor immunogenicity of bacterial polysaccharide. In addition to its primary role, which is to help generate a T cell-mediate long-lasting immune response directed against the carbohydrate antigen, the carrier protein in a glycoconjugate vaccine can also play an important role as a protective antigen. Among carrier proteins currently used in licensed conjugate vaccines, non-typeable Haemophilus influenzae protein D has been used as an antigenically active carrier protein. Our previous studies also indicate that some carrier proteins provide B cell epitopes, along with T cell helper epitopes. Herein we investigated the dual role of truncated rotavirus spike protein ΔVP8* as a carrier and a protective antigen. Capsular polysaccharide lipoarabinomannan (LAM), purified from Mycobacterium tuberculosis (M.tb), was chemically conjugated with ΔVP8*. Mouse immunization experiments showed that the resultant conjugates elicited strong and specific immune responses against the polysaccharide antigen, and the responses were comparable to those induced by Diphtheria toxoid (DT)-based conjugates. The conjugate vaccine induced enhanced antibody titers and functional antibodies against ΔVP8* when compared to immunization with the unconjugated ΔVP8*. Thus, these results indicate that ΔVP8* can be a relevant carrier protein for glycoconjugate vaccine and the glycoconjugates consisting of ΔVP8* with LAM are effective bivalent vaccine candidates against rotavirus and tuberculosis.