Chemistry of carbon compounds – Miscellaneous organic carbon compounds – C-metal
Patent
1983-12-05
1985-11-05
Phillips, Delbert R.
Chemistry of carbon compounds
Miscellaneous organic carbon compounds
C-metal
C07C10352
Patent
active
045512701
DESCRIPTION:
BRIEF SUMMARY
The invention relates to DNA framents coding for polypeptides containing at least one antigenic determinant of the papillomavirus, particularly of the HPV 1a type. It also relates to transformation products of such polypeptides, such as those resulting from the conjugation through covalent linkages of these polypeptides to support macromolecules and having immunogenic properties enabling their use, particularly either as means of diagnosing the presence or not of a papillomavirus in biological specimens, or as active principle of vaccines capable of immunizing a host against these papillomaviruses.
It is known that papillomaviruses are capable of infecting a large number of living species, man being among these. They are responsible for the production of benign tumors, particularly verrucas at the level of the epithelium that they colonize. These tumors which have mostly a regressive character can nonetheless in a certain number of cases give rise to a malignant transformation. Besides, the papillomaviruses have from the morphological aspect, been considered as related to polyoma viruses, such as the viruses known under the names SV 40, BKV, etc. These various types of virus have in fact in common an icosahedric capsid structure containing a double DNA helix associated with histones. In spite of the recognized impossibility of cultivating these papillomaviruses on epithelial cells or other cells, in a tissue culture, O. Danos et al. have recently succeeded in cloning the whole genome of the human papillomavirus, of the type 1a, in an Escherichia coli strain (Eur. J. Biochem., 109, 457-461 (1980)).
The present invention results from the discovery of certain sequences of the genome of this papillomavirus, which are capable of coding for peptides or polypeptides which can contain antigenic determinants enabling their use as an active principle of vaccines to be envisaged, as the case may be, after coupling with support macromolecules, at least for the smallest among them.
It is in this regard significant that these sequences are quite distinct from all sequences contained in the genomes of the polyoma viruses mentioned above. These sequences are revealed in fact to be borne by one only of the strands of the genome of the papillomavirus, as witnessed by sequence analyses of the whole genome of the papillomavirus.
The DNA fragment according to the invention can be redefined more generally, as consisting of that whose expression product in a suitable micro-organism contains at least one of the antigenic determinants of papillomaviruses, characterized in that it comprises a nucleotide sequence, itself contained or similar to that contained, either in the L1 region, or in the L2 region, or again for a part in the L1 region and for a part in the L2 region of that of the strands of the genome of a papillomavirus, such as the papillomavirus of the type 1a (HPV 1a) which comprises them and which are capable of coding for proteins of HPV 1a structures.
It is more particularly characterized in that it is constituted by a sequence of nucleotides capable of coding for one or some structure proteins of the virus or for a or some polypeptides having in common with these proteins a sequence containing at least one antigenic determinant characteristic of papillomaviruses, this nucleotide sequence being contained either in the L1 region, or in the L2 region, or again for a part in the L1 region and for a part in the L2 region, of that of the strands of the papillomavirus genome which includes them, from the genome of the papillomavirus and normally associated in the latter with said genome, and including at the most a hundred nucleotides.
For convenience of description, reference will be made below to the drawings in which:
FIGS. 1a, 1b and 1c represent the structure of a part of one of the strands of the HPV 1a genome, more particularly of that of which the sequence is read from the 5' and to the corresponding 3' end;
FIGS. 2a and 2b are diagrammatic representations of the parts which, in the respective strands of the genome
Danos Olivier
Katinka Michael
Yaniv Moshe
Institut Pasteur
Phillips Delbert R.
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