Common use of Safety Monitoring Clause in Contracts

Safety Monitoring. Vaccine formulations with both adjuvants were generally well tolerated. All animals maintained body weights within reference ranges of normal values for the entire duration of the study. There were also no major changes in behaviour, appetite or stool over the period of observation. Apart from palpable inguinal lymph nodes there were no notable local reactions (oedema, erythema, indurations) in all 18 study animals. Levels of aspartate transaminase in the DiCo/ISA immunisation group as well as alanine transaminase and bilirubin in the AM/ISA group showed slight increases on the days following immunisation but returned to normal levels within a week. There was an increase in creatinine levels a day after immunisation in the DiCo/HT group but these also returned to normal levels within a week. Creatinine levels in the DiCo/ISA group were however above normal values at the start of the study and remained at similar high levels throughout the observation period. Levels of blood iron decreased on the days following immunisation in the DiCo/HT group but also returned to normal levels within a week. All other measured clinical chemistry parameters were within normal reference ranges throughout the 70-day observation period. Of the parameters measured for haematology, increases in neutrophil count (and hence white blood cell count) were observed a day after each immunisation, but these again returned to normal values within a week. All other measured parameters were between normal ranges throughout the study. Generally, local reactions were limited to mild reddening of the injection site area, and these resolved within a few days. One animal in the AM/ISA group however developed stiffness in the upper leg muscle to a degree that limited movement of the left leg. This adverse event was first observed 14 days after the last immunisation (day 70) and had not resolved on day 126. Given this observation, which lasted for more than 56 days, the amount of discomfort to this animal was rated moderate to serious. IgG levels against seven AMA1 alleles and MSP119 at all sampling time points were determined using a harmonized ELISA. The three vaccine formulations induced appreciable levels of antibodies against the tested antigens and titres against all antigens increased in a similar manner and generally peaked on day 70, two weeks after the final vaccine injections were given. IgG titres against the FVO AMA1 allele at all time-points are presented in Figure 1 and day 70 titres against all antigens are presented in Figure 2. Beyond day 70, IgG titres in the two DiCo mix immunisation groups showed a decline that was statistically significantly lower on day 126 compared to day 70 levels (p < 0.05 for all AMA1 antigens, Student t test). Both the anti-AMA1 and anti-MSP119 levels for the AM/ISA group were however not significantly different on days 70 and 126 (p > 0.05, Student t test). Vaccine-induced IgG titres against all seven AMA1 capture antigens were generally highest in the DiCo/HT group by day 70. A comparison of the geometric mean titres, either for the same immunisation group against all AMA1 antigens, or for all groups against the same capture antigen, showed that there were no statistically significant differences (P > 0.05, one-way ANOVA). Anti- AMA1 IgG titres varied most amongst animals in the AM group, with four of the six animals having very low IgG titres against all antigens and the other two having exceptionally high titres (Figure 2).