TLR4-dependent adjuvant activity of Neisseria meningitidis lipid A

• Type of Material: Article
• Authors: Susu M Zughaier, Emory University; Liana Steeghs, Utrecht University; Peter van der Ley, Netherlands Vaccine Institute; David S Stephens, Emory University
• Language: English
• Date: 2007-05-30
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2007 Elsevier Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.vaccine.2007.03.029
• Title of Journal or Parent Work: Vaccine
• ISSN: 0264-410X
• Volume: 25
• Issue: 22
• Start Page: 4401
• End Page: 4409
• Grant/Funding Information: This work was supported by grant to Liana Steeghs from ZonMw, No, 906-02-058, and by NIH grant R01 AI033517 to David S. Stephens.
• Keywords: lipid A; TLR4; IgG titer; adjuvanticity
• Research Categories: Health Sciences, Immunology; Health Sciences, Epidemiology

Abstract

The adjuvant activity of Neisseria meningitidis serogroup B lipopoly(oligo)saccharide (LOS) from wild-type and genetically-defined LOS mutants and unglycosylated meningococcal lipid A was assessed in C3H/HeN and C3H/HeJ mice. Meningococcal lipid A, a weak agonist for TLR4/MD-2 in human macrophages, was found to have adjuvant activity similar to that of wild-type and KDO2-lipid A LOS in C3H/HeN mice. All meningococcal LOS structures as adjuvants induced high titers of IgG1, IgG2a and IgG2b but very little IgG3 to OMP compared to no adjuvant PBS controls. In addition, induced OMP antibodies were shown to have high bactericidal activity against serogroup B meningococci. Purified LOS and lipid A structures failed to induce any adjuvant activity in C3H/HeJ mice indicating that meningococcal LOS as an adjuvant was TLR4-dependent. Unglycosylated meningococcal lipid A because of its weak agonist activity for human macrophages and retention of adjuvant activity may be a candidate for use in serogroup B meningococcal OMP and OMV vaccines and for use as an adjuvant in other vaccines.