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 infection. 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 (2 ng) can elevate TNF production compared to treatment with WCA (p=0.06) or rhIL-12 (p=0.03) alone. The production of IFNγ was also increased but not in an antigen specific manner, suggesting perhaps a predominant Th(1) 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.
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Authors | Adam K A Wright, Ioanna Christopoulou, Sherouk El Batrawy, Jane Limer, Stephen B Gordon |
Journal | Immunobiology
(Immunobiology)
Vol. 216
Issue 10
Pg. 1143-7
(Oct 2011)
ISSN: 1878-3279 [Electronic] Netherlands |
PMID | 21601939
(Publication Type: Journal Article)
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Copyright | Copyright © 2011 Elsevier GmbH. All rights reserved. |
Chemical References |
- Adjuvants, Immunologic
- Antigens, Bacterial
- Cytokines
- Recombinant Proteins
- Interleukin-12
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Topics |
- Adjuvants, Immunologic
(administration & dosage)
- Animals
- Antigens, Bacterial
(administration & dosage, immunology)
- Bronchoalveolar Lavage Fluid
(cytology)
- Cytokines
(biosynthesis)
- Humans
- Interleukin-12
(administration & dosage)
- Leukocytes, Mononuclear
(drug effects, immunology)
- Lung
(cytology, immunology)
- Mice
- Recombinant Proteins
(administration & dosage)
- Streptococcus pneumoniae
(immunology)
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