Immunogenicity and Induction of Functional Antibodies in Rabbits Immunized with a Trivalent Typhoid-Invasive Nontyphoidal Salmonella Glycoconjugate Formulation
AuthorBaliban, Scott M.
Allen, Jessica C.
Amin, Mohammed N.
Levine, Myron M.
JournalMolecules (Basel, Switzerland)
PublisherMolecular Diversity Preservation International
MetadataShow full item record
AbstractTyphoid fever due to Salmonella Typhi and invasive nontyphoidal Salmonella (iNTS) infections caused by serovars Enteritidis (SE) and Typhimurium (STm) are major pediatric health problems in sub-Saharan Africa. Typhoid has high complication rates, and iNTS infections have high case fatality rates; moreover, emerging antimicrobial resistance is diminishing treatment options. Vi capsule-based typhoid conjugate vaccine (Typbar-TCV™), licensed in India and pre-qualified by the World Health Organization, elicits durable immunity when administered to infants, but no iNTS vaccines are licensed or imminent. We have developed monovalent SE and STm glycoconjugate vaccines based on coupling lipopolysaccharide-derived core-O polysaccharide (COPS) to phase 1 flagellin protein (FliC) from the homologous serovar. Herein, we report the immunogenicity of multivalent formulations of iNTS COPS:FliC conjugates with Typbar-TCV™. Rabbits immunized with the trivalent typhoid-iNTS glycoconjugate vaccine generated high titers of serum IgG antibody to all three polysaccharide antigens for which anti-COPS IgG antibodies were directed primarily against serogroup-specific OPS epitopes. Responses to SE and STm FliC were lower relative to anti-COPS titers. Post-vaccination rabbit sera mediated bactericidal activity in-vitro, and protected mice after passive transfer against challenge with virulent SE or STm Malian blood isolates. These results support accelerated progression to clinical trials.
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85055601793&origin=inward; http://hdl.handle.net/10713/9851
- Development of a glycoconjugate vaccine to prevent invasive Salmonella Typhimurium infections in sub-Saharan Africa.
- Authors: Baliban SM, Yang M, Ramachandran G, Curtis B, Shridhar S, Laufer RS, Wang JY, Van Druff J, Higginson EE, Hegerle N, Varney KM, Galen JE, Tennant SM, Lees A, MacKerell AD Jr, Levine MM, Simon R
- Issue date: 2017 Apr
- Immunogenicity and efficacy following sequential parenterally-administered doses of Salmonella Enteritidis COPS:FliC glycoconjugates in infant and adult mice.
- Authors: Baliban SM, Curtis B, Toema D, Tennant SM, Levine MM, Pasetti MF, Simon R
- Issue date: 2018 May
- Immunogenicity and protective efficacy against Salmonella C(2)-C(3) infection in mice immunized with a glycoconjugate of S. Newport Core-O polysaccharide linked to the homologous serovar FliC protein.
- Authors: Schuster O, Sears KT, Ramachandran G, Fuche FJ, Curtis B, Tennant SM, Simon R
- Issue date: 2019
- Sustained protection in mice immunized with fractional doses of Salmonella Enteritidis core and O polysaccharide-flagellin glycoconjugates.
- Authors: Simon R, Wang JY, Boyd MA, Tulapurkar ME, Ramachandran G, Tennant SM, Pasetti M, Galen JE, Levine MM
- Issue date: 2013
- Maternal Antibodies Elicited by Immunization With an O- Polysaccharide Glycoconjugate Vaccine Protect Infant Mice Against Lethal Salmonella Typhimurium Infection.
- Authors: Baliban SM, Curtis B, Amin MN, Levine MM, Pasetti MF, Simon R
- Issue date: 2019