Drug – bio-affecting and body treating compositions – Antigen – epitope – or other immunospecific immunoeffector – Combination of antigens from multiple viral species
Patent
1996-05-13
2000-02-15
Wortman, Donna
Drug, bio-affecting and body treating compositions
Antigen, epitope, or other immunospecific immunoeffector
Combination of antigens from multiple viral species
4242121, 4352351, 435239, A61K 39295, A61K 39165
Patent
active
060249625
DESCRIPTION:
BRIEF SUMMARY
Mumps is essentially a disease of childhood, which normally presents itself with only minor symptoms. However, in certain cases the clinical consequences of mumps infection are serious. For example, mumps is the most common cause of meningoencephalitis in children under 15 years of age in the UK, and a cause of permanent sensorineural deafness in childhood. Although 30-40% of natural mumps infection are symptomless, the very fact that salivary gland involvement can be unpleasant and that in the adult population mumps can cause 1st trimester abortions and orchitis of men as well as the neurological complications noted above, has led, in many countries, to the adoption of mass vaccination programs.
Mumps virus belonging to Paramyxoviridae is constituted by a single strand genomic RNA of the minus sense and is about 15.3 kb with the gene order 3' N-P-M-F-SH-HN-L5' (N-nucleocapsid protein, P=phosphoprotein, M=matrix protein, F=fusion protein, SH=potentially expressed as small hydrophobic protein, HN-haemagglutinin neuraminidase, L=large protein). Among various mumps strains, Jeryl-Lynn (B-level) is a live attenuated variant which has been characterised by sequence analysis of the F,P,HN,M genes.
Until recently, two mumps virus strains have been approved for vaccination against Mumps. These are Urabe Am 9 and Jeryl-Lynn. However in September 1992 the Urabe strain was withdrawn following a reported incidence of unacceptable level of side effects [European Journal of Pediatrics (1993) 152:387].
The Jeryl-Lynn strain has been sold commercially by Merck Sharp and Dohme for many years under the trade name "MumpsVax". The Jeryl-Lynn strain was obtained from a clinical sample of a patient suffering from mumps, by amniotic inoculation into embryonated hen's eggs (Proc. Soc. Exptl. Biol. Med. 123 (3) (1966)).
Afzal et al recently reported (J. of Gen. Virology 1993 74 917) that the Jeryl-Lynn strain used in mumps vaccines in the UK is in fact a mixture of two viruses, named JL-2 and JL-5.
Takeuchi et al Virology (1991) 181 p364-366 report that among different mumps strains there can be substantial nucleotide sequence variation at the SH gene level.
Afzal et al have emphasised that the present commercially available vaccine "MumpsVax" is made under carefully controlled conditions including a cell bank and passage limits and which are likely to preserve the proportion of the two variants from batch to batch. However with further passaging of the Jeryl-Lynn strain there is no guarantee that this balance between the two variants will be retained. Moreover it is difficult to assess the proportion of the two variants in any given batch of vaccine.
The present inventors have surprisingly identified a yet further isolate which differs from both JL-2 and JL-5 of Afzal et al. The difference was determined by nucleotide sequence analysis of the SH gene and regions surrounding it, more particularly the nontranslated intercistronic region 3' to the SH coding sequence and 5' to the HN gene. This isolate in clinical trials induces a higher zero conversion and has highest geometric mean titre of mumps antibody than the commercially available mumps vaccine.
Accordingly the present inventors provide an attenuated Jeryl-Lynn mumps strain containing the nucleotide sequence as set forth in FIG. 1. This sequence encodes the SH gene and the N terminus of the HN gene. The strain is herein referred to as SBB JL-1.
BRIEF DESCRIPTION OF THE DRAWING
In FIG. 1 there is shown the cDNA sequence of the JL-1 mumps virus isolate over the SH gene coding and SH-HN intergenic regions.
The present invention also provides a mumps vaccine comprising a substantially homogenous immunogenic Jeryl-Lynn isolate.
By substantially homogenous it is meant that the isolate is not contaminated with more than 10%, and preferably less than 5% and most preferably less than 1% of another Jeryl-Lynn isolate as defined by the sequence of the region set forth above. In a preferred embodiment of the invention, the vaccine contains a pure homogenous Jeryl-Lynn isolate i.e. dev
REFERENCES:
Elliott et al. "nucelotide sequence of the matrix, fusion and putative SH gene of mumps virus and their deduced amino acid sequences". Virus Research. vol. 12, pp 61-75, 1989.
Afzal, et al., "The Jeryl Lynn vaccine strain of mumps virus is a mixture of two distinct isolates", (1993), Journal of General Virology, vol. 74, p. 917-920.
Takeuchi, et al., "Variations of Nucleotide Sequences and Transcription of the SH Gene among Mumps Virus Strains", (1991), Virology, vol. 181, No. 1, pp. 364-366.
Colau Brigitte Desiree Alberte
Didelez Jean
Harford Nigel Maurice
Baumeister Kirk
King William T.
Kinzig Charles M.
SmithKline Beecham Biologicals (S.A.)
Wortman Donna
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