A randomized, double-blind, dose-finding Phase II study to evaluate immunogenicity and safety of the third generation smallpox vaccine candidate IMVAMUNE

Abstract

IMVAMUNE is a Modified Vaccinia Ankara (MVA)-based virus that is being developed as a safer 3rd generation smallpox vaccine. In order to determine the optimal dose for further development, a double-blind, randomized Phase II trial was performed testing three different doses of IMVAMUNE in 164 healthy volunteers. All three IMVAMUNE doses displayed a favourable safety profile, with local reactions as the most frequent observation. The 1 x 10(8)TCID(50) IMVAMUNE dose induced a total antibody response in 94% of the subjects following the first vaccination and the highest peak seroconversion rates by ELISA (100%) and PRNT (71%). This IMVAMUNE dose was considered to be optimal for the further clinical development of this highly attenuated poxvirus as a safer smallpox vaccine.

Figure 1. Disposition of subjects and cohorts analyzed

Out of 273 screened volunteers, 165 subjects were assessed as being eligible for enrolment and allocated to the three study groups. In total, ten subjects were excluded from the per-protocol analysis e.g. due to premature study discontinuation, violation of visit window and seropositivity at study start.

Figure 2. Correlation between the dose of IMVAMUNE® and ELISA and PRNT antibody titres

Subjects were vaccinated on Day 0 and 28 with three different doses of IMVAMUNE® (2×10⁷, 5×10⁷ and 1×10⁸ TCID₅₀) and blood was taken at various intervals and analysed for total and neutralising antibody responses to vaccinia by ELISA and PRNT respectively. The log10 of three different IMVAMUNE® doses was plotted against the log10 of the ELISA (Day 28: 1A, Day 42: 1C) and PRNT titres (Day 28: 1B, Day 42: 1D).