Acellular pertussis vaccines
Coordinated efforts on the part of manufacturers, research institutions and national regulatory authorities have led to the development of a variety of acellular pertussis vaccines that appear to be effective in clinical studies. These positive developments have led to the need for international guidelines to assure the quality of this new generation of pertussis vaccines.
The vaccines tested in studies of clinical efficacy have been mainly products where the acellular pertussis component has been formulated with diphtheria and tetanus antigens.
There is as yet no consensus about the antigenic composition of an ideal acellular pertussis vaccine. Accellular pertussis vaccines currently available from different manufacturers should be considered as different and unique products because of the presence of one or more different components (chemically or genetically detoxified pertussis toxin, filamentous haemagglutinin (FHA), 69kDa outer-membrane protein (also know as pertactin), fimbrial-2 and fimbrial-3 antigens) in different concentrations, and with different degrees of adsorption to different adjuvants. In addition, these individual antigens may be derived from different strains of Bordetella pertussis and have been purified by different methods. For these reasons the protective efficacy in humans of various manufacturers' products may be based on different mechanisms, which complicates the direct comparison of the protective activity of various products and new formulations by means of simple laboratory tests. Indeed, no unequivocal immunological correlates of protection against pertussis have yet been demonstrated, nor has a generally accepted animal model to predict clinical efficacy been validated.
In the light of this difficulty, any change in the manufacture or formulation of an acellular pertussis vaccine that has been shown to be safe and effective in clinical studies should be treated with the utmost caution. While, ideally, the safety and efficacy of a new formulation should be demonstrated in the target population, it is becoming increasingly difficult to undertake efficacy trials. Consequently, other criteria may be accepted by a national regulatory authority as predictors of clinical performance. One possibility is to demonstrate the induction of immune responses equivalent to those induced by an approved homologous acellular pertussis vaccine of proven safety and efficacy. However, additional information about the physicochemical and immunological characteristics of a new vaccine formulation will also be necessary to demonstrate its equivalence with a homologous approved pertussis vaccine. Such criteria should be discussed with the national regulatory authority.
In view of these considerations, it is essential that research to identify immunological markers of protection against pertussis be actively supported and pursued, and that there be rigorous post-licensing monitoring of vaccines for safety and effectiveness.
BS.2251 Guidelines on the quality, safety and efficacy of biotherapeutic protein products prepared by recombinant DNA technology: Appendix 7. Regulatory assessment of approved rDNA-derived biotherapeutics
BS.2252 Recommendations to assure the quality, safety and efficacy of recombinant human papillomavirus virus-like particle vaccines
- Expert Committee on biological Standardization, WHO Headquarters, Geneva, Switzerland, 12-16 October 2015
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