Medeva Europe Limited

Medeva Holdings Bv

Acambis Research Limited

Carlos Estenio Hormaeche

Mohammed Anjam Khan

Gordon Dougan

Steven Neville Chatfield

Hesta Varey McNeill

Bernardo Villarreal-Ramos

The invention provides a DNA molecule comprising a promoter sequence operably linked to a DNA sequence encoding first and second proteins linked by a hinge region wherein in that the promoter sequence can be one having activity which is induced in response to a change in the surrounding environment and the first protein can be Tetanus toxin C fragment or one or more epitopes thereof. The invention also provides intermediate molecules having a promoter operably linked to a DNA sequence encoding a first antigenic sequence and a hinge region, and at or adjacent the 3&prime;-end thereof one or more restriction sites for the introduction of a second anti-genic sequence. In addition, the invention provides replicable expression vectors containing the DNA fusion proteins expressed therefrom, bacterial transformed with the vectors and the use of the bacteria, in vaccines.

Expression of recombinant fusion proteins in attenuated bacteria

The invention provides a DNA construct comprising a DNA sequence encoding a fusion protein of the formula: TetC-(Z) -Het, wherein: TetC is the C fragment of tetanus toxin, or a protein comprising the epitopes thereof; Het is a heterologous protein, Z is an amino acid, and a is zero or a positive integer, provided that (Z) does not include the sequence Gly-Pro. The invention also provides replicable expression vectors containing the constructs, bacteria transformed with the constructs, the fusion proteins per se and vaccine compositions formed from the fusion proteins or attenuated bacteria expressing the fusion proteins.

Vaccine compositions

The invention relates to DNA constructs encoding a safe, selectable marker, other than an antibiotic resistance marker, vectors and/or cells including said constructs; and vaccines based on said constructs for use in animals and particularly humans. The safe, selectable marker being a marker that confers resistance to an agent, other than an antibiotic, which would otherwise deleteriously affect the growth of a cell in which said construct was placed.

Non antibiotic selectable markers for live vaccines

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Newcastle upon Tyne, United Kingdom

Carlos Estenio Hormaeche