Jack Melling

The complete amino acid sequence of the Clostridium botulinum type A neurotoxin, deduced by nucleotide sequence analysis of the encoding gene

A 26-mer oligonucleotide probe was synthesized (based on the determined amino acid sequence of the N-terminus of the Clostridium botulinum type A neurotoxin, BoNT/A) and used in Southern blot analysis to construct a restriction map of the region of the clostridial genome encompassing BoNT/A. The detailed information obtained enabled the cloning of the structural gene as three distinct fragments, none of which were capable of directing the expression of a toxic molecule. The central portion was cloned as a 2-kb PvuII-TaqI fragment and the remaining regions of the light chain and heavy chain as a 2.4-kb ScaI-TaqI fragment and a 3.4-kb HpaI-PvuII fragment, respectively. The nucleotide sequence of all three fragments was determined and an open reading frame identified, composed of 1296 codons corresponding to a polypeptide of 149 502 Da. The deduced amino acid sequence exhibited 33% similarity to tetanus toxin, with the most highly conserved regions occurring between the N-termini of the respective heavy chains. Conservation of Cys residues flanking the position at which the toxins are cleaved to yield the heavy chain and light chain allowed the tentative identification of those residues which probably form the disulphide bridges linking the two toxin subfragments.

Anthrax: the disease in relation to vaccines

The authors trace the origins and history of anthrax and anthrax vaccines. They describe the aetiology and pathogenesis of the disease and the variety of symptoms which result from infection. The authors relate the early work performed by Pasteur, the development of existing vaccines and the efficacy of these vaccines, and predict the type of non-living vaccines which may be used to combat anthrax in the future.

Herpes simplex virus genital infection of the female guinea pig as a model for the evaluation of an experimental vaccine

Substantial protection against herpes simplex type 2 (HSV 2) infection of the female guinea pig genital tract was provided by immunization with an experimental HSV 2 vaccine prepared from the plasma membranes of infected MRC-5 cells. Protection was evaluated in terms of the modification of histopathological lesions and clinical signs and in changes in viral replication and serological responses in vaccinated and control animals.