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Infect Immun, July 1998, p. 3183-3189, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mucosal Delivery of Murine Interleukin-2 (IL-2) and IL-6 by Recombinant Strains of Lactococcus lactis Coexpressing Antigen and Cytokine

Lothar Steidler,1 Karen Robinson,2 Lisa Chamberlain,2 Karin M. Schofield,2 Erik Remaut,1 Richard W. F. Le Page,2 and Jeremy M. Wells2,*

Department of Molecular Biology, Flanders Inter-University Institute for Biotechnology, and University of Ghent, B-9000 Ghent, Belgium,1 and Cortecs Centre for Vaccine Discovery, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, United Kingdom2

Received 7 October 1997/Returned for modification 12 January 1998/Accepted 10 April 1998

Lactococcus lactis is a nonpathogenic and noncolonizing bacterium which is being developed as a vaccine delivery vehicle for immunization by mucosal routes. To determine whether lactococci can also deliver cytokines to the immune system, we have constructed novel constitutive expression strains of L. lactis which accumulate a test antigen, tetanus toxin fragment C (TTFC), within the cytoplasmic compartment and also secrete either murine interleukin-2 (IL-2) or IL-6. When mice were immunized intranasally with various different expression strains of L. lactis, the anti-TTFC antibody titers increased more rapidly and were substantially higher in mice immunized with the bacterial strains which secreted IL-2 or IL-6 in addition to their production of TTFC. This adjuvant effect was lost when the recombinant strains of L. lactis were killed by pretreatment with mitomycin C and could therefore be attributed to the secretion of IL-2 or IL-6 by the recombinant lactococci. These results provide the first example of the use of a cytokine-secreting, noninvasive experimental bacterial vaccine vector to enhance immune responses to a coexpressed heterologous antigen and point the way to experiments which will test the possible therapeutic efficacy of this mode of cytokine delivery.

* Corresponding author. Mailing address: Cortecs Centre for Vaccine Discovery, Department of Pathology, University of Cambridge, Tennis Court Rd., Cambridge CB2 1QP, United Kingdom. Phone: 44 1223 330245. Fax: 44 1223 333346. E-mail: jmw16{at}mole.bio.cam.ac.uk.

Infect Immun, July 1998, p. 3183-3189, Vol. 66, No. 7
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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