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Molecules 2018, 23(7), 1749; https://doi.org/10.3390/molecules23071749

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

1
Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA
2
Fina Biosolutions LLC, 9430 Key West Ave. Suite 200, Rockville, MD 20850, USA
3
Bharat Biotech International Limited, Hyderabad 500 078, Telangana, India
*
Author to whom correspondence should be addressed.
Academic Editors: Paul Kovac, Peng Xu and Helene Pfister
Received: 21 May 2018 / Revised: 12 July 2018 / Accepted: 14 July 2018 / Published: 17 July 2018
(This article belongs to the Special Issue Conjugate Vaccines from Carbohydrate Antigens)
Full-Text   |   PDF [1366 KB, uploaded 17 July 2018]   |  

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. 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. View Full-Text
Keywords: lipopolysaccharide; Vi; glycoconjugate; antibody; Salmonella; flagellin; vaccine; iNTS; typhoid lipopolysaccharide; Vi; glycoconjugate; antibody; Salmonella; flagellin; vaccine; iNTS; typhoid
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Baliban, S.M.; Allen, J.C.; Curtis, B.; Amin, M.N.; Lees, A.; Rao, R.N.; Naidu, G.; Venkatesan, R.; Rao, D.Y.; Mohan, V.K.; Ella, K.M.; Levine, M.M.; Simon, R. Immunogenicity and Induction of Functional Antibodies in Rabbits Immunized with a Trivalent Typhoid-Invasive Nontyphoidal Salmonella Glycoconjugate Formulation. Molecules 2018, 23, 1749.

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