Oral vaccines delivered via enticing bait can help increase overall rabies protection in areas with large populations of free-ranging dogs. Rabies, an endemic zoonotic disease found across the globe, causes roughly 60,000 human fatalities every year, mostly in Africa and Asia. The rabies virus is spread through contact with the saliva of an infected animal. More than 99% of human rabies cases are transmitted through dog bites; 46% of those affected are children.

Developed countries have had success in eliminating rabies in dogs through parenteral mass vaccination programs, but developing nations lack the awareness and resources to control rabies effectively. In areas with canine populations that are not accessible for parenteral vaccination, oral vaccination is beneficial to increase protection against the rabies virus.

According to the World Health Organization, at least 70% of the canine population must be vaccinated to break the cycle of transmission from dogs to humans. Oral vaccination of dogs (OVD) via a palatable bait offers numerous benefits; however, because baited oral vaccines may come in contact with numerous other species, including humans, strict safety and efficacy requirements exist. Researchers from the French Agency for Food, Environmental and Occupational Health & Safety recently reviewed major studies evaluating vaccine candidates for OVD, including modified-live, attenuated and recombinant vaccines.

Developing a vaccine

OVD developers must establish a candidate vaccine, evaluate its safety and efficacy in laboratory trials, choose a palatable bait matrix and conduct field trials in target populations to ensure all aspects of the vaccine are in line with international standards.

To establish OVD efficacy, animals vaccinated with a successful vaccine candidate are challenged with a well-characterized street virus of canine origin at a concentration known to induce rabies in 80% of control animals. The duration of immunity in both laboratory and field conditions is also examined according to international guidelines.

Numerous factors are considered when choosing a bait matrix, including palatability, shape, size and texture as well as local preferences of both the target canine populations and the humans administering the bait. For example, chicken head baits were very successful in Tunisia and Guatemala, but dogs in Turkey were less likely to eat chicken head baits if they were typically fed table scraps. Additionally, dog owners in the Philippines were worried that chicken head baits would encourage their dogs to kill free-roaming poultry in the area. Logistics of bait distribution strategies should also be considered.

A look at candidate vaccines

For this study, several vaccine candidates were evaluated in laboratory and field settings as recommended by regulatory agencies. Due to the potential for human contact with the saliva of vaccinated dogs, salivary excretions were examined for viral replication. V-RG (vaccinia-rabies-glycoprotein), SAD (Street-Alabama-Dufferin) Bern, SAG2 (SAD Avirulent Gif) and SPBNGAS-GAS excretions were positive for viral replication at several timepoints. SAD B19 did not test positive for viral replication in saliva.

Reversion to virulence was not detected in SAG2, V-RG or SAD B19. Two human cases of vaccinia-like illness were reported in people with immune suppression or dysfunction who were exposed to dogs vaccinated with the recombinant vaccine V-RG.

Viral neutralizing antibodies were detected in dogs vaccinated with numerous candidate vaccines, and protection against rabies challenge was demonstrated in dogs that lacked viral neutralizing antibodies following vaccination with SAG2. Efficacy in dogs receiving oral vaccines was evaluated at least six months post vaccination with SAG2, VRC-RZ2 and CAV-2-E3D-RGP (at two years).

The logistics of bait production and distribution was also evaluated. Ideally, bait production should be low in cost and done locally in large numbers, and baits should be examined in the field to ensure proper delivery and uptake by the target species. Chicken head baits in Tunisia and Guatemala, köfte (meatball) baits in Turkey, cooked pig intestines in the Philippines and cooked cow intestine on the U.S. Navajo Nation reservation were most successful.  

Delivery methods should factor in thermostability of vaccines, and uneaten baits should be removed following the window of thermostability for each vaccine. Two methods of bait distribution were evaluated: distribution to dog owners and bait placement for wildlife. Distribution to dog owners was time-consuming but enabled safe administration of the vaccines to owned dogs in Tunisia. Baits distributed to predetermined stations to target wildlife were successful in Morocco, Tunisia and Turkey. 

Adverse effects were reported with the use of SAG2 OVD in Finland, where hundreds of thousands of baits were distributed annually. Nine cases of gastrointestinal upset and related behavioral signs were reported in dogs that consumed the baits while hunting.

Take-home points

OVD is a useful tool in the elimination of rabies worldwide, but safety concerns exist. The vaccine strains V-RG and SAG2 have been used extensively in the field with acceptable safety and efficacy profiles. Parenteral vaccines utilize inactivated viruses and are less expensive to produce than the self-replicating biologics currently used in OVD. In regions where stray dogs are in close contact with humans, the likelihood of human contact with baits as well as with recently vaccinated dogs is much higher than with wildlife vaccine campaigns. With increasing use of immunosuppressive agents and immune modulators in humans, there is potential for unknown effects from OVD using self-replicating biologics. The effective clearance of rabies in any region will likely require the use of parenteral vaccines and OVD coupled with population control of stray dogs and strong public education campaigns to meet the international goal of rabies eradication in humans by 2030.

1. Cliquet F, Guiot A-L, Aubert M, et al. Oral vaccination of dogs: a well-studied and undervalued tool for achieving human and dog rabies elimination. Vet Res 2018;49:61.

Dr. Bohn received her PhD and MS from Georgia State University and has been a practicing veterinary nurse for nearly 20 years. Ms. Stoessel is a veterinary assistant and medical writing intern. They provide freelance medical writing services through Bohn Communications.