In-Depth Characterization of Live Vaccines Used in Europe for Oral Rabies Vaccination of Wildlife

Abstract

Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.

Long-Term Immunogenicity and Efficacy of the Oral Rabies Virus Vaccine Strain SPBN GASGAS in Foxes

“…Although there is no doubt about the effectiveness of live-attenuated rabies vaccines of the 1st and 2nd generation under field conditions, and despite more than 750 million baits distributed between 1978 and 2018 [5,6,7], the continued use of vaccines at least of the 1st generation has been questioned [8]. To overcome limitations of those vaccines regarding safety, e.g., residual pathogenicity for rodent species [9,10,11,12,13] and observed vaccine-induced rabies in target and non-target animals [6,14,15,16,17], high genetic diversity within certain commercial vaccine strains [18,19,20], temperature stability and ineffectiveness of the oral route in rabies reservoirs such as raccoons and skunks [21,22,23]; alternative vaccines with, for instance, a higher safety profile have been developed. Recombinant vaccines constructed from heterologous virus vectors like the vaccinia virus and human adenovirus type 5 that express the RABV G [24,25,26,27,28,29] have been widely used in ORV programs to combat rabies in wildlife, in particular in foxes and raccoons in Western Europe and North America [2,30,31,32,33,34,35].…”

Comparison of intra- and inter-host genetic diversity in rabies virus during experimental cross-species transmission

“…In contrast, little is known about the relationship between RABV intra-host diversity, including subpopulation differentiation in different hosts and tissues, and the patterns and processes of evolutionary change observed in natura . Although several studies have investigated the nature of RABV genetic diversity following adaptation to cell lines [10, 11], to experimental hosts [10, 12–14], or in the context of vaccines [15–17], to date no strong host-specific molecular fingerprints have been identified using either Sanger [18] or next-generation sequencing (NGS) [7, 19].…”

Rabies-based vaccine induces potent immune responses against Nipah virus

“…Indeed, the rabies strain upon which our recombinant NIPARAB is based (SAD B19) has been successfully used as a live oral vaccine for wildlife in Europe. 50 Our data have shown that live NIPARAB does not cause pathogenicity in mice, even when administered at a high dose (5.75log 10 ffu) intranasally, and has the added benefit of bivalency toward rabies, a devastating pathogen that widely affects both humans and wildlife in the same geographic regions where NiV outbreaks occur. Moreover, INAC NIPARAB is immunogenic after a single dose of unadjuvanted vaccine (Fig.…”