An assessment of shedding with the oral rabies virus vaccine strain SPBN GASGAS in target and non-target species

Abstract

A safety requirement for live vaccines is investigating possible shedding in recipients since the presence of replication competent vaccine in secretions could result in direct and indirect horizontal transmission. This is especially relevant for oral rabies vaccine baits that are deliberately distributed into the environment. In the current study, survival of an oral rabies virus vaccine, SPBN GASGAS, was examined in excretions from different target and non-target species; red fox, raccoon dog, small Indian mongoose, raccoon, striped skunk, domestic dog, domestic cat and domestic pig. Saliva - and (pooled) fecal samples collected at different time points after oral administration of the vaccine strain were examined for the presence of viral RNA (rt-PCR). All PCR-positive and a subset of PCR-negative samples were subsequently investigated for the presence of infectious virus by isolation in cell culture (RTCIT). Up to 7 days post vaccine administration viral RNA could be detected in 50 of 758 fecal samples but no infectious virus was detected in any of the examined PCR-positive fecal samples. In contrast, RNA-fragments were detected in 248 of 1053 saliva swabs for an extended period (up to 10 days) after vaccine administration, but viable virus was only present during the first hours post vaccine administration in 38 samples. No infectious vaccine virus was isolated in saliva swabs taken 24 h or more after vaccine administration. Hence, no active shedding of the vaccine virus SPBN GASGAS after oral administration occurred and the virus isolated during the initial hours was material originally administered and not a result of virus replication within the host. Thus, potential horizontal transmission of this vaccine virus is limited to a short period directly after vaccine bait uptake. It can be concluded that the environmental risks associated with shedding after distributing vaccine baits containing SPBN GASGAS are negligible.

Responsiveness of various reservoir species to oral rabies vaccination correlates with differences in vaccine uptake of mucosa associated lymphoid tissues

“…Taken together, the data corroborate the hypothesis of rapid clearance of attenuated rabies virus vaccines in the oral cavity as described before regardless of the target species 37,58 . The mechanism behind this could be related to the activation of NFκB related genes, which might lead to a rapid clearance at the primary sites of infection as shown for SPBN GASGAS 59 .…”

Safety studies with the oral rabies virus vaccine strain SPBN GASGAS in the small Indian mongoose (Herpestes auropunctatus)

“…Interestingly, no virus was found in the palatine tonsils as this was determined as the primary site of uptake after oral administration [ 42 ]. Finally, no infectious vaccine virus was detected in fecal samples and saliva swabs collected during the overdose and dissemination study, although viral RNA was detected in several of these samples [ 19 ]. All mongooses of which blood samples were collected seroconverted with the exception of one animal (overdose study), indicating successful vaccine uptake (Tables 2 - 4 ).…”

“…The vaccine strain SPBN GASGAS is derived from SAD L16, a cDNA clone of the oral rabies virus vaccine strain SAD B19 [ 19 , 20 ]. SPBN GASGAS lacks the pseudogene (Ψ) and has been genetically modified by site-directed mutagenesis at the amino acid positions 194 and 333 of the glycoprotein [ 21 ].…”

“…Rabies lyssavirus is considered relatively thermo-instable and will rapidly lose its infectivity when exposed to elevated temperatures [ 18 ]. Shedding of vaccine virus in saliva and feces has been investigated during the dissemination and overdose studies; these results have been published previously and will not be presented here [ 19 ]. It was shown that the vaccine strain SPBN GASGAS was completely innocuous for the small Indian mongoose, irrespective of the route of administration and dose.…”

In Vivo Safety Studies With SPBN GASGAS in the Frame of Oral Vaccination of Foxes and Raccoon Dogs Against Rabies

“…As domestic dogs live in very close association with humans a dissemination study in dogs was determined essential. Also, secretions like saliva and feces from target and non-target species that received the vaccine virus should be examined for the presence of the vaccine virus; the results of these shedding studies have been published previously ( 3 ). The results of the above-mentioned studies showed that the vaccine virus SPBN GASGAS did not induce any adverse reaction in target – and non-target species and thus meets the minimal safety requirements set by the regulatory authorities.…”