Vaccination to break plague transmission in Madagascar

Barry Moore

Dr Barry Moore
Reader of Biophysical Chemistry
Pure & Applied Chemistry, University of Strathclyde (UK)

Collaborators:

Dr Minoarisoa Rajerison, Institut Pasteur Madagascar (Madagascar)
Dr Diane Williamson, DSTL (UK)

Summary

The most serious outbreak of plague in modern times occurred in Madagascar in 2018, with in excess of 2600 cases and an estimated case fatality rate of 8.9% (WHO 2018). In Madagascar as well as in other parts of the world, plague causes seasonal outbreaks, with risk of epidemic potential and transmission to new regions. These seasonal outbreaks are caused by flea-vectored transmission from wildlife reservoirs (principally rats).  There is no approved vaccine for plague and antibiotic therapy needs to be given early after exposure to infection, to be fully effective. Here we propose to test a sub-unit vaccine in a novel formulation for efficacy against a Malagasy strain of the causative bacterium, Yersinia pestis.  In a previous liquid formulation, this sub-unit vaccine has been shown to be efficacious in mice and macaques against the reference Y.pestis Co92 type strain and was also shown to be safe and immunogenic in a Phase 1 clinical trial (Williamson et al 2005).  Here, we have reformulated the vaccine for distribution to an LMIC, as a stable, dry powder which is reconstituted just before use.  We will test the vaccine under laboratory conditions at the Institute Pasteur in Madagascar in rats derived from either plague-infected or non-infected areas of the island, prior to challenge with a circulating Malagasy strain of plague. The objective is to determine if this vaccine can induce immunity in the local rat population, preventing transmission to man. Production of a vaccine will mitigate development of AMR resistant strains of plague.