Three Rs achievements in vaccinology

Most vaccines for human use are complex biological mixtures consisting of one or more vaccine antigens and an adjuvant product to enhance the immune response. Consequently, vaccine batch release is based on extensive statutory required quality control emphasizing final lot testing. Traditionally, this area of research and testing requires large numbers of animals while levels of pain and suffering are high compared to other purposes of animal experimentation. This overview will discuss some of the opportunities for Three Rs alternatives in this field. Particular attention will be give to vaccine quality control, being the major target for Three R research. It is concluded that progress has been made. However, obstacles may limit effective acceptance or implementation in routine use. Several of these obstacles will be discussed. Finally, this paper will elaborate on a new strategy in vaccine quality control that ultimately might lead to a substantial reduction of animal use, the so-called 'consistency approach'. In the consistency approach emphasis is given to aspects such as in-process testing, the implementation of Good Manufacturing Practice (GMP) and to Quality Assurance (QA). The new strategy particularly focuses on a set of non-animal test models including physicochemical methods, immunochemical methods and in vitro models to monitor key aspects of antigen quantity and quality and of specific immune responses.