Lactococcus lactis : high‐level expression of tetanus toxin fragment C and protection against lethal challenge

Jeremy M. Wells*, Peter W. Wilson, Pamela M. Norton, Michael J. Gasson, Richard W.F. Le Page

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

151 Citations (Scopus)

Abstract

To determine if the food‐grade bacterium Lactococcus lactis holds promise as a vaccine antigen delivery vector we have investigated whether this bacterium can be made to produce high levels of a heterologous protein antigen. A regulated expression system has been developed which may be generally suitable for the expression of foreign antigens (and other proteins) In L. lactis. The system utilizes the fast‐acting T7 RNA polymerase to transcribe target genes, and provides the first example of the successful use of this polymerase in a Gram‐positive bacterium. When the performance of the expression system was characterized using tetanus toxin fragment C (TTFC) up to 22% of soluble cell protein was routinely obtained as TTFC. Mice immunized subcutaneously with L. lactis expressing TTFC were protected from lethal challenge with tetanus toxin. These results show for the first time that L. lactis is able to express substantial quantities of a heterologous protein antigen and that this organism can present this antigen to the Immune system in an immunogenic form.

Original languageEnglish
Pages (from-to)1155-1162
Number of pages8
JournalMolecular Microbiology
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 1993
Externally publishedYes

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