**3. Vaccination of Wildlife**

The vaccine was originally envisaged for human use, and steps were taken in this direction in collaboration with the Institut Mérieux. However, there was reluctance to introduce a new vaccinia-based vaccine for human use because smallpox, the original target of vaccinia, had recently been declared eradicated by the World Health Organization (WHO) [13]. A committee of international experts including WHO representatives, who met in Bethesda, MD, in November 1984, did not envisage early human use [14]. However, because rabies is transmitted to humans principally from domestic dogs – that themselves acquire the infection from foxes (in Europe), and from raccoons and coyotes (in North America) – the next step was to try the new vaccine out for efficacy in animals. With support from Philippe Desmettre at the Institut Mérieux, Transgène was in touch with Pierre-Paul Pastoret in Belgium and colleagues at the French Ministry of Agriculture Rabies Research Station in Malzéville close to Nancy, and this was soon followed by the demonstration that oral administration of the vaccine (108 pfu) to foxes (**Figure 4**) gave complete protection against lethal challenge, and almost complete protection following administration in home-made bait [15], quickly followed by oral protection of raccoons in the USA by colleagues at the Wistar Institute [16].

This was expanded to small-trials followed by large-scale campaigns to eradicate sylvatic rabies in Europe and North America by dropping baits (e.g., chicken heads or artificial baits) seeded with live recombinant virus from helicopters (**Figure 3B**) according to a carefully planned routine (taking in mind the number of wildlife species per square kilometer, and the transmission factor R – what percentage of animals do we need to vaccinate to block propagation? – of current interest given the COVID pandemic). It worked. The first trials (**Figure 5**) demonstrated wide uptake by foxes and downturn of rabies cases. Using this vaccine, rabies has now been widely eliminated in many European countries; substantial reductions in rates of rabies in wildlife

**Figure 4.** *Experimental vaccination of foxes, Malzéville, France, ca 1986 (image collection M.P.K.).*

#### **Figure 5.**

*First wildlife vaccination campaigns. Baits containing VRG were prepared from fish oil and protein. (A) Test areas in Belgium, 1987–1988. Vaccines were distributed at 15–50 baits per km2 ; uptake ranged from 27% at day 4 to 94% at day 223 (image collection M.P.K.). (B) Larger-scale field trial in a 2200 km2 area of Belgium; distribution was at 15 baits per km2 ; the area was vaccinationed three times (1990–1991). Baits contained a tetracycline biomarker, and uptake determined from the presence of tetracycline (Tet; UV fluorescence in jaw) was 81% after the third phase. The single rabid fox detected after the campaign, at the periphery of the baited area, was Tet-negative. Image adapted, with permission, from [17].*
