US 7,320,861 B2
Polyvalent vaccine against diseases caused by papilloma viruses, method for the production and the use thereof
Lutz Gissmann, Wiesloch (Germany); Kai Pohlmeyer, Fitzbek (Germany); and Martin Müller, Neckargemünd (Germany)
Assigned to Deutsches Krebsforschungszentrum Stiftung des Oeffentlichen Rechts, Heidelberg (Germany)
Appl. No. 10/485,454
PCT Filed Jul. 26, 2002, PCT No. PCT/EP02/08360
§ 371(c)(1), (2), (4) Date Aug. 31, 2004,
PCT Pub. No. WO03/011335, PCT Pub. Date Feb. 13, 2003.
Claims priority of application No. 101 37 102 (DE), filed on Jul. 30, 2001.
Prior Publication US 2005/0004054 A1, Jan. 06, 2005
Int. Cl. C12Q 1/68 (2006.01)
U.S. Cl. 435—6  [435/345; 435/69.1] 13 Claims
 
1. A method of making a polyvalent vaccine against a plurality of papilloma virus types, comprising:
(a) injecting into at least one mammal a plurality of expression vectors, each expression vector comprising at least one papilloma virus L1 structural protein gene clone,
wherein each L1 structural protein gene clone comprises DNA that encodes at least a portion of a L1 structural protein of a papilloma virus, and
wherein the at least a portion of a L1 structural protein of a papilloma virus comprises at least one randomly generated heterologous sequence, which is derived from the coding sequence of a naturally occurring epitope by the substitution of one or more nucleotides and which substitutes the naturally occurring epitope sequence or which is present additionally to the naturally occurring epitopes of the L1 structural gene;
(b) obtaining serum from the at least one mammal,
(c) testing the serum to detect antibodies against the particles of papilloma virus, and
(d) identifying said at least one L1 structural protein gene clone that leads to an antibody response against a plurality of papilloma virus types.