Twenty year experience of the oral rabies vaccine SAG2 in wildlife: a global review - PubMed (original) (raw)

Review

Twenty year experience of the oral rabies vaccine SAG2 in wildlife: a global review

Philippe Mähl et al. Vet Res. 2014.

Abstract

The SAG2 vaccine (RABIGEN® SAG2) is a modified live attenuated rabies virus vaccine, selected from the SAD Bern strain in a two-step process of amino acid mutation using neutralizing monoclonal antibodies. The strain is genetically stable and does not spread in vivo or induce a persistent infection. Its absence of residual pathogenicity was extensively demonstrated in multiple target and non target species (such as wild carnivores and rodent species), including non-human primates. The efficacy of SAG2 baits was demonstrated according to the EU requirements for the red fox and raccoon dog. The use of safe and potent rabies vaccines such as SAG2 largely contributed to the elimination of rabies in Estonia, France, Italy and Switzerland. Importantly, these countries were declared free of rabies after few years of oral vaccination campaigns with SAG2 baits distributed with an appropriate strategy. The excellent tolerance of the SAG2 vaccine has been confirmed in the field since its first use in 1993. No safety issues have been reported, and in particular no vaccine-induced rabies cases were diagnosed, after the distribution of more than 20 million SAG2 baits in Europe.

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Figures

Figure 1

Figure 1

Construction of the SAG2 strain. ERA = Evelyn Rokitnicki Abelseth, Mab = monoclonal antibody. The parental SAD strain was isolated from the salivary glands of a rabid dog in the USA during 1935, which was passaged in mice, chick embryos, and various cell lines and was re-named ERA (Evelyn Rokitnicki Abelseth). The SAD Bern strain is a cell-adapted derivative of the ERA strain. The SAD Bern strain was cultivated in the presence of monoclonal antibodies binding specifically to one of the two major antigenic sites (antigenic site III) of the rabies virus glycoprotein, involved in virus pathogenicity. Under the selective pressure of these monoclonal antibodies, only variants of SAD Bern bearing an amino-acid substitution at the critical position 333 of the rabies virus glycoprotein escaped neutralisation in culture. An avirulent mutant, SAG1 (for SAD Avirulent Gif), in which arginine at position 333 was substituted by serine, was isolated from SAD Bern with monoclonal antibody (Mab) 50 AD1. The SAG2 strain was constructed from SAD Bern in a two-step selection procedure using neutralizing monoclonal antibodies. First, a mutant strain (SK) was selected from SAD Bern, where the arginine at position 333 was replaced by lysine. SAG2, a non pathogenic mutant resistant to neutralisation by monoclonal antibody 50 AC1 was selected from SK, where the lysine at position 333 was replaced by a glutamic acid. Thus, SAG2 can be considered as a double avirulent mutant, since the codon GAA, which codes for glutamic acid, differs from the codon AGA from SAD Bern (coding for arginine) by two nucleotides.

Figure 2

Figure 2

SAG2 Vaccine bait. This figure shows the bait, the PVC/aluminium blister containing the liquid suspension of the SAG2 strain. SAG2 bait and the blister are both labelled with “Rabies vaccine, do not touch”.

Figure 3

Figure 3

Animal rabies cases before and after vaccination campaigns with SAG2 in Switzerland, France, Estonia, Italy. The impact of the vaccination with SAG2 baits on the number of terrestrial animal rabies cases is illustrated in four countries, Switzerland, France, Estonia and Italy.

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