Immunogenicity and Induction of Functional Antibodies in Rabbits Immunized with a Trivalent Typhoid-Invasive Nontyphoidal Salmonella Glycoconjugate Formulation

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Scott M BalibanRaphael Simon

Abstract

Typhoid 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. Po...Continue Reading

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Citations

Jul 22, 2020·Human Vaccines & Immunotherapeutics·Giulia Piccini, Emanuele Montomoli
Jul 30, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·William L StillKaren L Kotloff
Jul 30, 2020·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Scott M BalibanRichard Malley
Jan 7, 2021·International Immunology·Divy DhingraDipshikha Chakravortty

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Methods Mentioned

BETA
enzyme-linked
flow filtration
ELISA
electrophoresis
Assay

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