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rhIL-12 as adjuvant augments lung cell cytokine responses to pneumococcal whole cell antigen

Wright, Adam, Christopoulou, Ioanna, El Batrawy, Sherouk, Limer, Jane and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2011) 'rhIL-12 as adjuvant augments lung cell cytokine responses to pneumococcal whole cell antigen'. Immunobiology, Vol 216, Issue 10, pp. 1143-1147.

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Abstract

Conjugate pneumococcal vaccines offer suboptimal protection against mucosal infections and are restricted in serotype and geographical coverage.New protein-based vaccines using conserved pneumococcal antigens and better mucosal adjuvant technology are urgently needed. Interleukin-12(IL-12) has shown efficacy as a pneumococcal protein vaccine adjuvant in murine models of pneumococcal linfection. Systemic administration of recombinant human (rh) IL-12 to humans, however, has been associated with adverse clinical and laboratory side effects. Inhaled forms of IL-12 have improved the safety profiles in humans, as suggested by animal models. Here we evaluated rhIL-12 as an adjuvant on ex vivo human BAL cells when stimulated with pneumococcal whole cells. We show that co-incubation of ex vivo human BAL cells with pneumococcal whole cell antigen (WCA) and a low dose of rhIL-12 (2ng) can elevate TNF production compared to treatment with WCA (p = 0.06 )or rhIL-12 (p = 0.03) alone. The production of IFN _ was also increased but not in an antigen specific manner, suggesting perhaps a predominant Th1 response. Our data suggest that 100–200-fold lower doses of inhaled rhIL-12 than those previously tested for systemic use may be adequate in a phase 1 study and commend further evaluation of rhIL-12 as a potential mucosal adjuvant in human vaccine studies

Item Type: Article
Uncontrolled Keywords: Adjuvant, Cytokine, IL-12, Streptococcus pneumoniae, Vaccine
Subjects: QW Microbiology and Immunology > Immunotherapy and Hypersensitivity > QW 805 Vaccines. Antitoxins. Toxoids
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Digital Object Identifer (DOI): https://doi.org/10.1016/j.imbio.2011.04.003
Depositing User: Users 43 not found.
Date Deposited: 06 Sep 2011 08:38
Last Modified: 07 Jun 2022 11:09
URI: https://archive.lstmed.ac.uk/id/eprint/2095

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