Salmonella synthesizing 1-monophosphorylated lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity

Qingke Kong, David A. Six, Kenneth L. Roland, Qing Liu, Lillian Gu, C. Michael Reynolds, Xiaoyuan Wang, Christian R H Raetz, Roy Curtiss

Research output: Contribution to journalArticle

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Abstract

The development of safe live, attenuated Salmonella vaccines may be facilitated by detoxification of its LPS. Recent characterization of the lipid A 1-phosphatase, LpxE, from Francisella tularensis allowed us to construct recombinant, plasmid-free strains of Salmonella that produce predominantly 1-dephosphorylated lipid A, similar to the adjuvant approved for human use. Complete lipid A 1-dephosphorylation was also confirmed under low pH, low Mg2+ culture conditions, which induce lipid A modifications. lpxE expression in Salmonella reduced its virulence in mice by five orders of magnitude. Moreover, mice inoculated with these detoxified strains were protected against wild-type challenge. Candidate Salmonella vaccine strains synthesizing pneumococcal surface protein A (PspA) were also confirmed to possess nearly complete lipid A 1-dephosphorylation. After inoculation by the LpxE/PspA strains, mice produced robust levels of anti-PspA Abs and showed significantly improved survival against challenge with wild-type Streptococcus pneumoniae WU2 compared with vector-only-immunized mice, validating Salmonella synthesizing 1-dephosphorylated lipid A as an Ag-delivery system.

Original languageEnglish (US)
Pages (from-to)412-423
Number of pages12
JournalJournal of Immunology
Volume187
Issue number1
DOIs
StatePublished - Jul 1 2011

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Lipid A
Salmonella
Lipopolysaccharides
Salmonella Vaccines
Francisella tularensis
Attenuated Vaccines
Streptococcus pneumoniae
Phosphoric Monoester Hydrolases
Virulence
Plasmids
Survival
pneumococcal surface protein A

ASJC Scopus subject areas

  • Immunology

Cite this

Salmonella synthesizing 1-monophosphorylated lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity. / Kong, Qingke; Six, David A.; Roland, Kenneth L.; Liu, Qing; Gu, Lillian; Reynolds, C. Michael; Wang, Xiaoyuan; Raetz, Christian R H; Curtiss, Roy.

In: Journal of Immunology, Vol. 187, No. 1, 01.07.2011, p. 412-423.

Research output: Contribution to journalArticle

Kong, Q, Six, DA, Roland, KL, Liu, Q, Gu, L, Reynolds, CM, Wang, X, Raetz, CRH & Curtiss, R 2011, 'Salmonella synthesizing 1-monophosphorylated lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity', Journal of Immunology, vol. 187, no. 1, pp. 412-423. https://doi.org/10.4049/jimmunol.1100339
Kong, Qingke ; Six, David A. ; Roland, Kenneth L. ; Liu, Qing ; Gu, Lillian ; Reynolds, C. Michael ; Wang, Xiaoyuan ; Raetz, Christian R H ; Curtiss, Roy. / Salmonella synthesizing 1-monophosphorylated lipopolysaccharide exhibits low endotoxic activity while retaining its immunogenicity. In: Journal of Immunology. 2011 ; Vol. 187, No. 1. pp. 412-423.
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