Rabies Virus Antibodies from Oral Vaccination as a Correlate of Protection against Lethal Infection in Wildlife

Abstract

Both cell-mediated and humoral immune effectors are important in combating rabies infection, although the humoral response receives greater attention regarding rabies prevention. The principle of preventive vaccination has been adopted for strategies of oral rabies vaccination (ORV) of wildlife reservoir populations for decades to control circulation of rabies virus in free-ranging hosts. There remains much debate about the levels of rabies antibodies (and the assays to measure them) that confer resistance to rabies virus. In this paper, data from published literature and our own unpublished animal studies on the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies vaccines, are examined as correlates of protection against lethal rabies infection in captive challenge settings. Analysis of our studies suggests that, though serum neutralization test results are expected to reflect in vivo protection, the blocking enzyme linked immunosorbent assay (ELISA) result at Day 28 was a better predictor of survival. ELISA kits may have an advantage of greater precision and ability to compare results among different studies and laboratories based on the inherent standardization of the kit format. This paper examines current knowledge and study findings to guide meaningful interpretation of serology results in oral baiting monitoring.

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

“…Our quantitative serological results suggest a correlation with responsiveness to oral vaccination in various species for RFFIT, whereby mean VNA titres of responsive species were significantly higher (p < 0.05) as opposed to low responsive species (Table 3). Even taking this limited number of animals into account this corroborates previous findings 53 .…”

“…In our study we were required to use a very high vaccine dose (10 8.0 FFU/mL) to increase the likelihood to observe any differences in vaccine uptake in MALT of the oral cavity of the various species at all. This could be the reason why all animals regardless of species exhibited RABV specific antibodies by day 10 pi (Table 3) as measured by the standard RFFIT 53 and the more sensitive ELISA 53,54 , irrespective of the identification of infected cells in the t. palatina. Therefore, other tissues in the oropharyngeal cavity must have been involved in virus uptake and subsequent interaction with the immune system.…”

“…For the detection of virus neutralising antibodies (VNA), collected blood samples were analysed by rapid fluorescent focus inhibition test (RFFIT) as described elsewhere 53 . Binding antibodies were detected by rabies virus specific inhibition ELISA according to manufacturer specifications (BioPro Rabies ELISA Ab kit, O.K.…”

Rabies surveillance in wild mammals in South of Brazil

“…The cut‐off point to consider a wild animal as seropositive is somehow controversial. For example, raccoons show less variation titres than other wild species, indicating that further evaluation of negative samples by species is necessary for assignment of cut‐offs for lower limit of detection of an assay (Moore et al, ).Investigators assessing exposure of free‐ranging wild animals to RABV occasionally use a cut‐off point of 0.50 IU/ml (Almeida et al, ), which mimics the one recommended for humans by the World Health Organization as a measure of adequate seroconversion after vaccination (WHO Position Paper, ). This avoids positive results from cross‐reactive antibodies or non‐specific inhibition of RABV that can be misinterpreted as very low levels of RVNA.…”

“…The cut-off point to consider a wild animal as seropositive is somehow controversial. For example, raccoons show less variation titres than other wild species, indicating that further evaluation of negative samples by species is necessary for assignment of cut-offs for lower limit of detection of an assay (Moore et al, 2017).Investigators assessing exposure of free-ranging wild animals to RABV occasionally use a cut-off point of 0.50 IU/ml (Almeida et al, 2001), which mimics the one recommended for humans by the World Health…”