By day 2 volunteer measurements were 34 and 28 mm and clinic measurements 20 and 12 mm (left and right arms respectively). The volunteer reported that the Dorsomorphin molecular weight total duration of swelling was 13 days. Of vaccine-related AEs (detailed in Online Table B), 394 (68%) were local to the vaccine site and 183 (32%) were systemic. The median AE duration (and interquartile range, IQR) was 7 (3–12) and 2 (1–2) days for local and systemic vaccine-related AEs respectively. As expected, local vaccine responses (such as pain, redness, swelling and local tenderness)

occurred with almost every vaccine dose. The median duration (and IQR) of pain was 2 (1–3.25) days and most (88.2%) were mild. Systemic responses (e.g. headache, myalgia and tiredness) occurred frequently after vaccination (Fig. 1). Myalgia was most common, reported by 48% of volunteers. For the single vaccine dose-escalation groups 1–5, the frequency of local AEs did not alter as dose increased, but more systemic AEs (mostly mild in severity) were seen with increasing dose in MVA vaccinated volunteers (Fig. 2). The frequency of local AEs also varied little with successive vaccinations in the three-dose heterologous prime-boost groups FFM and MMF, but the proportion of AEs graded

moderate increased with successive doses in the MMF group (Fig. 3). There was no clear trend in AE duration during vaccination in these groups (Fig. 3d). Eleven volunteers (32%) had at least one blood result falling outside the study reference ranges during follow up, but none of these were associated Raf inhibitor with clinical symptoms and only two warranted referral to the general practitioner and for repeat testing or investigation (mild hyperbilirubinaemia at 28 μmol/L and a low haemoglobin of 9.8 g/dL which resolved at repeat testing). Three doses of MVA-PP and two doses of FP9-PP were assessed in single-dose small groups (n = 3), primarily for safety, before deciding on doses to be used in the larger prime-boost groups.

Immunogenicity for these groups was low, as expected in the absence of a booster dose, but pre-vaccination responses were also relatively high (Fig. 4). For MVA-PP there was a suggestion that immunogenicity was lower at the high dose (5 × 108 pfu). In deciding the dose to be used in the prime-boost groups, the following factors were considered: firstly, although all doses appeared safe, the frequency of systemic AEs was higher with increasing MVA-PP dose; secondly, there was no clear dose advantage for MVA-PP at high dose; and thirdly, the possibility of encountering anti-vector immunity cross-reactive between the different poxviruses. It was therefore decided that for each of the prime-boost groups, the low vaccine dose (1 × 108 pfu) would be used to prime and the intermediate dose (2 × 108 pfu) to boost.