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A Ladefoged

Publications and source records attributed to A Ladefoged.

10 recordsLinked to original sources
PubMed1999

Development of the Mycobacterium bovis BCG vaccine: review of the historical and biochemical evidence for a genealogical tree.

The original Mycobacterium bovis Bacillus Calmette Guérin vaccine strain has developed into several different substrains which have been used for production of BCG vaccines throughout the world since 1921. Based on the latest genetic and antigenic knowledge, as well as the early literature reports on BCG vaccination, we are able to fit the different pieces of the BCG puzzle together and outline the origin of the different substrains of M. bovis BCG. The BCG vaccine substrains analysed demonstrate two distinct patterns, with an abrupt change consisting of a loss of several genes and altered biochemical characteristics in strains originating from Institut Pasteur after 1927. Further evidence from the literature is provided that a change occurred in virulence of the BCG parent strain at Institut Pasteur in the late 1920s. Based on this information a genealogical tree is proposed and discussed.

BCG Vaccine↗
PubMed1984

Does trypsin extract soluble antigen meet the criteria of immunogenicity without allergenicity?

We were unable to confirm the finding of Crowle that TESA possesses the attribute of immunogenicity and absence of allergenicity which are desired in a non-living antituberculosis vaccine. This disagreement could be a function of the particular lot of TESA examined and/or differences in the animal test systems used for the assay of protective potency. The relative contribution of these two possibilities could be determined by the simultaneous assay of a potent TESA product in different laboratories using different animal models.

Animals↗
PubMed1978

Combined vaccination with BCG and toxoid antigens.

Simultaneous vaccination with different antigens has been widely practised in recent years. A notable example is percutaneous smallpox vaccination together with the intradermal injection of BCG. In contrast, the potentially even more time-saving procedure of combined vaccination (i.e., with vaccines mixed prior to injection) has been tried on only a very limited, experimental scale. Combined vaccination with a mixture of BCG and toxoids has not been suggested before. Such a mixed vaccine, with diphtheria and tetanus toxoids, was used in experiments in vitro and in vivo.No deleterious effect of toxoids on BCG was found in terms of reduction in oxygen uptake, germination rate, or counts of viable particles. The dose-response relationships (delayed hypersensitivity and skin reactivity) for BCG with and without added toxoids were compared in guinea pigs and no differences were found. The antibody response in guinea pigs to toxoids mixed with BCG or with aluminium hydroxide was measured following both primary and booster immunization. The primary response to toxoids was lower with BCG than with aluminium hydroxide. In booster immunization, the response was identical for the two mixtures.It appears that not only is a mixture of toxoids and BCG innocuous (given intradermally) but also BCG may have an adjuvant effect on the production of antibodies to the toxoids. Further experimentation is needed, first in the guinea pig model and later in pilot trials in man, to establish suitable dose levels. Furthermore, since BCG may act as an adjuvant both in producing antibodies and in the cell-mediated response to the toxoids, it would be desirable to clarify the possible interaction of these two immune responses in protection against disease.

Animals↗
PubMed1976

Tuberculin sensitivity in guinea-pigs after vaccination with varying doses of BCG of 12 different strains.

In several previously reported studies a number of BCG strains, including those most widely used in vaccine production, were ranked according to their in vivo activity in various experimental models in rodents and to the local and allergic response that they provoked in children. In this report, 12 strains are ranked in terms of tuberculin conversion in guinea-pigs according to the minimum sensitizing dose. For 10 of these strains, this minimum dose is very low, ranging from 5 to 50 culturable particles. Thus the traditional practice of tuberculin-testing guinea-pigs that have been vaccinated with a full human dose of BCG (of the order of one million culturable particles) has such a low discriminating power that it is useless as a routine test for currently used vaccines. The ranking obtained in this model was largely but not completely in accordance with similar rankings in other models. The Tokyo strain and, to some extent, the London strain ranked comparatively lower than they do in children. The pronounced lack of virulence of the Prague strain was confirmed.

Animals↗
PubMed1970

The virulence of some strains of BCG for golden hamsters. Further studies.

In principle, a strain of BCG used for the preparation of live vaccine should retain a moderate residual virulence. The inoculation of golden hamsters with large doses of BCG causes progressive, fatal disease but not all strains are equally active. In a previous paper, the present authors gave data from experiments with 9 BCG strains; in this report, 4 additional strains, three of which are in routine use in vaccine-production laboratories, are compared with one of the strains used in the previous experiments. The five strains differ widely in their ability to kill hamsters and were ranked in nearly the same order in two identically designed experiments. The differences in virulence found between strains derived relatively recently from a single mother strain were particularly noticeable. These differences were sometimes accompanied by striking changes in the growth characteristics of the strains with a lower virulence. The hypothesis that the lower virulence in such cases is a sign of genetic mutation is consistent with the general biological experience that virulence is often lost in vitro but that it practically never increases.

Animals↗
PubMed1970

The protective effect in bank voles of some strains of BCG.

The bank vole, like the guinea-pig, can be immunized against tuberculosis with very small doses of BCG, presumably because BCG is sufficiently virulent for both these species to multiply freely until the immunization of the animal has reached a maximum. Large doses of BCG induce an earlier, but not an ultimately stronger, immunity. However, the smallest immunizing dose is not the same for all BCG strains and this is a feature that may be used to differentiate strains. In the studies reported by the authors, the smallest immunizing dose for the bank vole was estimated for 11 BCG strains, some of them widely used in man. The results indicate potency ratios of 20: 1 between the strongest and the weakest strains. The ranking of strains in terms of the smallest immunizing dose was found to be correlated in most, but not in all, cases with a previously reported ranking of the lethal effects of the various strains in golden hamsters. The implications of these findings for production requirements and for reference preparations of BCG are discussed.

Animals↗
PubMed1968

The virulence of some strains of BCG for golden hamsters.

Although the injection of a large dose of BCG causes progressive, fatal disease in the Syrian golden hamster, not all BCG strains are equally active in this respect. It has been suggested that a strain to be used for vaccinating human beings should not be too weakly virulent in the hamster.Nine BCG strains, some of them widely used for BCG production, were compared with regard to their virulence for hamsters. Five of the strains were found to be of about the same high virulence; the other 4 were less virulent.Of the strains derived from the BCG that was used with success in the BCG trial conducted in Great Britain more than 15 years ago, some are more virulent for hamsters than others. It is suggested that virulence is easily lost but not gained when strains are maintained in vitro. Thus, less virulent strains would have deviated from the original protective strain, and for this reason may be less acceptable for vaccine production.

Animals↗