Ferguson, R. 3Rs improvements in the Bexsero® (Meningitis B) vaccine. Animal Technology and Welfare 16(2), 150-152.

Bexsero® is a new vaccine in the UK which since September 2015 has been added to the childhood immunisation programme for the prevention of Meningitis B. The in-vivo test as performed in Biological Services Division (BSD) uses female CD1 mice and involves an intra-peritoneal injection of 0.5 ml of sample or reference vaccine on day 0. This is followed by a boost on day 21 and then terminal bleed on day 35. The vaccines contain Aluminium Hydroxide adjuvant (ALOH), which were originally serially diluted using the same adjuvant. Unfortunately, adverse effects considered to be pain-related are commonly observed in the mice post injection. Post-mortem, some animals are observed to have small internal lesions. It is thought that the adverse effects and lesions are caused by the ALOH adjuvant. We have successfully introduced several refinements to improve the animals’ overall experience during study. The first refinement is the use of saline instead of ALOH to dilute the vaccine. This resulted in an equivalent or increased dose response curve (improving the assay) and a lower number of animals displaying adverse effects. Where effects were seen, there was a significant reduction in animal discomfort and also in the duration of the adverse effects observed. The second refinement is to provide analgesia. To help alleviate any discomfort, Calpol®, a sweetened fruit flavoured paracetamol based solution is administered via the drinking water. It is provided (under veterinary guidance) for 24 hours prior to and remains for 24 hours post injection. Long bottle spouts are also used to allow for easier access to the Calpol® solution should the mice experience adverse effects. The third refinement is the development of score sheets that are specific to the Bexsero® test to allow accurate recording of adverse effects and actual severity recording at end of test.