Report on results of a collaborative assay of BCG vaccines organized by the International Association of Biological Standardization

Sekhuis, V.M.; Freudenstein, H; Sirks, J. L.

doi:10.1016/0092-1157(77)90004-x

Cited by 17 publications

(3 citation statements)

References 7 publications

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“…The M. bovis BCG strains used in this study were Pasteur 1173P2, cloned in 1962 from a single colony (15); Glaxo 1077, derived from an ampoule of Danish BCG vaccine (strain passage 1077) in the 1950s; and Japanese 172 and the Russian and Prague strains, which were derived from the original Pasteur uncloned BCG culture strain. All these strains were sent to us freeze-dried by the World Health Organization as seed lots (30) and stored at Ϫ30ЊC.…”

Section: Methodsmentioning

confidence: 99%

Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains

et al. 1996

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Among the various parameters which may contribute to Mycobacterium bovis BCG vaccination efficiency, the choice of the vaccine strain may play an important role. In the present study, we therefore compared the immunogenicity of five different BCG strains that are commonly used for BCG vaccine production (Glaxo 1077, Japanese 172, Pasteur 1173P2, Prague, and Russian strains). The comparison of the growth capacity of these BCG strains in BALB/c and C3H mice demonstrated that a great difference exists between the capacity of various BCG strains to multiply and persist in target organs. A much lower recovery of BCG could be shown in mice immunized with Prague and Japanese BCG strains. T-cell responses of BCG-immunized mice were also examined by analyzing T-cell proliferative responses, cytokine production, delayed-type hypersensitivity responses, and cytotoxic activity. All these assays demonstrated that BCG immunization induced strong CD4 ؉ T-cell responses, mostly of the Th1 type, as demonstrated by interleukin-2 and gamma interferon production. These studies also demonstrated that there are differences between BCG strains in stimulating these T-cell responses. A lack of induction of cytotoxic activity was observed following immunization with the Japanese strain. Lower anti-purified protein derivative antibody responses were also observed after intravenous or oral immunization with this BCG strain. Finally, the protective activity of these BCG strains was tested by measuring the capacity of immunized mice to eliminate recombinant Pasteur and Japanese BCG strains which expressed ␤-galactosidase. The results of these experiments clearly demonstrated that the Prague and Japanese strains were unable to protect mice against a second mycobacterial challenge whereas mice immunized with the Glaxo, Pasteur, or Russian strain eliminated the recombinant BCG very efficiently. Altogether, the results of the present study strongly support the view that there are considerable differences in the immunogenicity of various BCG vaccine strains and that these differences may play a major role in BCG vaccination efficiency.

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Section: Methodsmentioning

confidence: 99%

Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains

et al. 1996

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“…For nearly 6 decades it has been appreciated that BCG substrains differ in their ability to interfere with the hematogenous dissemination of a challenge dose of M. tuberculosis in animal models [ 35 ]. Furthermore, relatively virulent BCG substrains capable of persisting in relatively high titer in the organs of mice protect best in small animal models and thus have been considered by some authorities to have greater vaccine potency [ 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. Accordingly, we wondered whether our modifications to BCG that reduced the in vivo persistence of 4dBCG would also reduce the ability of 4dBCG to protect against hematogenous dissemination.…”

Section: Resultsmentioning

confidence: 99%

A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

Shoen¹,

DeStefano²,

Hager

et al. 2013

Vaccines

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Early attempts to improve BCG have focused on increasing the expression of prominent antigens and adding recombinant toxins or cytokines to influence antigen presentation. One such modified BCG vaccine candidate has been withdrawn from human clinical trials due to adverse effects. BCG was derived from virulent Mycobacterium bovis and retains much of its capacity for suppressing host immune responses. Accordingly, we have used a different strategy for improving BCG based on reducing its immune suppressive capacity. We made four modifications to BCG Tice to produce 4dBCG and compared it to the parent vaccine in C57Bl/6 mice. The modifications included elimination of the oxidative stress sigma factor SigH, elimination of the SecA2 secretion channel, and reductions in the activity of iron co-factored superoxide dismutase and glutamine synthetase. After IV inoculation of 4dBCG, 95% of vaccine bacilli were eradicated from the spleens of mice within 60 days whereas the titer of BCG Tice was not significantly reduced. Subcutaneous vaccination with 4dBCG produced greater protection than vaccination with BCG against dissemination of an aerosolized challenge of M. tuberculosis to the spleen at 8 weeks post-challenge. At this time, 4dBCG-vaccinated mice also exhibited altered lung histopathology compared to BCG-vaccinated mice and control mice with less well-developed lymphohistiocytic nodules in the lung parenchyma. At 26 weeks post-challenge, 4dBCG-vaccinated mice but not BCG-vaccinated mice had significantly fewer challenge bacilli in the lungs than control mice. In conclusion, despite reduced persistence in mice a modified BCG vaccine with diminished antioxidants and glutamine synthetase is superior to the parent vaccine in conferring protection against M. tuberculosis. The targeting of multiple immune suppressive factors produced by BCG is a promising strategy for simultaneously improving vaccine safety and effectiveness.

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“…BCG vaccines in rubber-stoppered vials previously showed a lower stability than those conserved in ampoules (82,121), although this seems not to be the case with currently supplied vaccines that use rubber stoppers.…”

Section: Packing Bcg Vaccinesmentioning

confidence: 93%

Effect of Freezing on Oxytocin Ampules

2013

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Report on results of a collaborative assay of BCG vaccines organized by the International Association of Biological Standardization

Cited by 17 publications

References 7 publications

Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains

Comparison of immune responses of mice immunized with five different Mycobacterium bovis BCG vaccine strains

A Modified Bacillus Calmette-Guérin (BCG) Vaccine with Reduced Activity of Antioxidants and Glutamine Synthetase Exhibits Enhanced Protection of Mice despite Diminished in Vivo Persistence

Effect of Freezing on Oxytocin Ampules

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