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

Susan M Moore,Thomas Müller,Christine Ellis,Conrad M Freuling,Ad Vos,Amy Gilbert,Jeannette Kliemt

doi:10.3390/tropicalmed2030031

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 In this paper, data from published literature and our own unpublished animal studies on the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies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.

Highlights

Rabies is caused by infection with lyssaviruses, which are a group of single-stranded negativesense RNA viruses in the family Rhabdoviridae
The objective of this paper is to quantitatively examine the induction of rabies binding and neutralizing antibodies following oral immunization of animals with live attenuated or recombinant rabies vaccines, as correlates of protection against lethal rabies infection in captive challenge settings by reviewing both published literature and our own unpublished animal studies
Published peer-reviewed journal articles concerning oral rabies vaccination in wildlife that included rabies antibody measurement after oral vaccination and challenge were reviewed in an attempt to identify a protective level per rabies antibody

Summary

Introduction

Rabies is caused by infection with lyssaviruses, which are a group of single-stranded negativesense RNA viruses in the family Rhabdoviridae. There remains much debate about the levels of rabies antibodies that confer resistance to rabies virus infection and, antibody levels are one key index of resistance to challenge in animal models [6,7], no single cutoff level of rabies antibody is recognized as being invariably protective [8]. This is due to repeated observations that small fractions of animals presenting detectable levels of antibody prior to challenge can still succumb to rabies infection, and some seronegative animals survive challenge [8,9]

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