Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

<jats:title>ABSTRACT</jats:title><jats:p>Invasive nontyphoidal<jats:named-content content-type="genus-species">Salmonella</jats:named-content>(iNTS) disease is a neglected disease with high mortality in children and HIV-positive individuals in sub-Saharan Africa, caused primarily by Africa-specific strains of<jats:named-content content-type="genus-species">Salmonella enterica</jats:named-content>serovars Typhimurium and Enteritidis. A vaccine using GMMA (generalized modules for membrane antigens) from<jats:italic>S.</jats:italic>Typhimurium and<jats:italic>S.</jats:italic>Enteritidis containing lipid A modifications to reduce potential<jats:italic>in vivo</jats:italic>reactogenicity is under development. GMMA with penta-acylated lipid A showed the greatest reduction in the level of cytokine release from human peripheral blood monocytes from that for GMMA with wild-type lipid A. Deletion of the lipid A modification genes<jats:italic>msbB</jats:italic>and<jats:italic>pagP</jats:italic>was required to achieve pure penta-acylation. Interestingly, Δ<jats:italic>msbB</jats:italic>Δ<jats:italic>pagP</jats:italic>GMMA from<jats:italic>S.</jats:italic>Enteritidis had a slightly higher stimulatory potential than those from<jats:italic>S.</jats:italic>Typhimurium, a finding consistent with the higher lipopolysaccharide (LPS) content and Toll-like receptor 2 (TLR2) stimulatory potential of the former. Also, TLR5 ligand flagellin was found in<jats:named-content content-type="genus-species">Salmonella</jats:named-content>GMMA. No relevant contribution to the stimulatory potential of GMMA was detected even when the flagellin protein FliC from<jats:italic>S.</jats:italic>Typhimurium was added at a concentration as high as 10% of total protein, suggesting that flagellin impurities are not a major factor for GMMA-mediated immune stimulation. Overall, the stimulatory potential of<jats:italic>S.</jats:italic>Typhimurium and<jats:italic>S.</jats:italic>Enteritidis Δ<jats:italic>msbB</jats:italic>Δ<jats:italic>pagP</jats:italic>GMMA was close to that of<jats:named-content content-type="genus-species">Shigella</jats:named-content><jats:italic>sonnei</jats:italic>GMMA, which are currently in phase I clinical trials.</jats:p>

Original publication

DOI

10.1128/cvi.00023-16

Type

Journal article

Journal

Clinical and Vaccine Immunology

Publisher

American Society for Microbiology

Publication Date

04/2016

Volume

23

Pages

304 - 314