Rabies is a serious disease, so making sure your dog or cat is protected with vaccination remains a necessity. As with any vaccine, however, the potential adverse reactions can also be serious. So what’s the answer?

Rabies is a serious and usually fatal disease. This means that vaccinating our dogs and cats against this disease is a necessity. However, the duration of immunity (DOI) for rabies vaccines is proving to be far longer than the one or three years that current laws demand for re-vaccination. The Rabies Challenge Fund studies, which aim to better define the DOI conveyed by rabies vaccine in dogs, and push for changes in the legislation, are now at six and seven years post-vaccination — and the initial results have shown the vaccinated dogs in the study to be still protected from rabies.

Adverse events caused by vaccines

Countless animals have been vaccinated repeatedly for rabies and the other common serious infectious viral and bacterial diseases, without obvious untoward effects.^1-3 But we still need to be aware of the potential for adverse events (AE) and decide what constitutes “acceptable” harm.^1-3

Vaccines typically contain immunologic adjuvants that act to accelerate, prolong or enhance antigen-specific immune responses when used together with specific vaccine antigens.¹ Adjuvants are incorporated into vaccines to enhance their immunogenicity, but this increases the risk of autoimmune and inflammatory AE. In killed inactivated vaccines available for human and animal use, potent adjuvants are included to produce a more sustained humoral immune response and thus compete favorably with the longer protection typically afforded by modified-live virus (MLV) products.

Killed inactivated vaccines still cause reactions

Although killed inactivated products make up about 15% of the veterinary biologicals used, they have been associated with 85% of  post-vaccination reactions, mainly because of the acute adverse responses induced by the adjuvants.¹ Debate continues about the relative merits and safety of killed vaccines that contain adjuvants  versus MLV vaccines.

Studies have shown that the simultaneous administration of even two or three adjuvants can overcome genetic resistance to autoimmunity.  Because vaccines are viewed as inherently safe and non-toxic, toxicity studies are often excluded from their regulatory safety assessments. Children and young animals are especially at risk, being more vulnerable to toxicity than adults; and they are regularly exposed to more vaccine adjuvants than adults. Adjuvants impact the central nervous system at all levels, and can do so by changing gene expression. Further, it is now known that the neuro-immune axis, heavily targeted by adjuvants, plays a key role in brain development and immune function.¹

Documented AE from the adjuvants used in human vaccines, especially those containing aluminum and thimerosal (mercury salt), continue to appear in the literature.¹ These metals can inflict both immune and inflammatory responses, defined since 2011 as the “autoimmune syndrome induced by adjuvants” (ASIA syndrome). Reported neurotoxicity in humans affects learning, memory, cognition and speech, increases seizure propensity, and alters behavior by increasing anxiety, insomnia, dementia and confusion.¹

Exposure to aluminum and mercury is widespread. These metals are found in many sources of drinking water and as food additives (especially in processed “fast” convenience foods). They’re used in many cosmetics, as well as field, lawn and garden fertilizers and herbicides, and in pharmaceuticals, including vaccines. Therefore, they can accumulate in the bodies of most, if not all, species.   Aluminum and mercury are not only neurotoxins, but are also immunotoxic, genotoxic, endocrine and glucose disrupters, as well as pro-oxidant and pro-inflammatory agents.

Other issues with rabies vaccines

• Vaccinating dogs with polyvalent vaccines containing rabies virus, or rabies vaccine alone, has been shown to induce production of antithyroglobulin autoantibodies, an important finding with implications for the subsequent development of ¹
• Post-vaccinal polyneuropathy is a recognized entity occasionally associated with the use of canine distemper and rabies vaccines, but any vaccine could presumably be This can result in clinical signs such as muscular atrophy, interruption of neuronal control of tissue and organ function, muscular excitation, incoordination and weakness, as well as seizures.
• Killed, inactivated vaccines, such as those for rabies virus, can trigger immediate and delayed AE. While there may be immediate hypersensitivity reactions, other acute events tend to occur 24 to 72 hours, or up to a week afterwards, and as long as 45 days later in the case of more delayed Documented reactions include behavioral aggression and separation anxiety; destruction and shredding of clothing and bedding; obsessive behavior, barking, fearfulness, self-mutilation and tail chewing; pica, eating wood, stones, earth and feces; seizures and epilepsy; fibrosarcomas at the injection site; and autoimmune diseases such as those affecting bone marrow and blood cells, the joints, eyes, skin, kidney, liver, bowel, and CNS.^1,2

Based on data from the US, reactions to rabies vaccines are the most common group of AE reported to the United States Department of Agriculture (USDA) Center for Veterinary Biologics (CVB). Currently, 14 rabies vaccines are labeled for use in dogs, but only two do not contain the thimerosal (mercury) adjuvant/preservative.

Rabies virus neutralizing antibody titers

A review of rabies challenge studies indicates that there is a positive correlation between rabies virus neutralizing antibody (RVNA) titers and the level of protection after virus challenge.¹ Pre-exposure vaccination, coupled with a RVNA titer at or above 0.5 IU/mL, indicates greater assurance of protection than does the animal’s current vaccination status.  Because we may not know if an animal has been exposed to rabies virus, rabies experts recommends that rabies titers be done routinely for dogs and cats.  When rabies titers drop below 0.5 IU/ml, giving a rabies booster is the prudent decision. Anamnestic rabies antibody responses occur immediately after giving a rabies booster.¹

At present, the best protection against rabies in both individual animals and the species population is to have all of them vaccinated against rabies. (Note: rabies exemptions may be approved on a case-by- case basis with written justification from the primary care veterinarian.) Meanwhile, the Rabies Challenge Fund will continue its studies, with the aim of eventually changing the laws from requiring boosters every  one or three years, to five and seven years.

Some stats on rabies

The World Health Organization (WHO) estimates that ten million people worldwide require medical treatment against rabies each year after being exposed to an animal suspected of or having rabies. There are nearly 40,000 human post-exposure prophylaxis treatments administrated each year in the US, which represents 100 million dollars in costs for treatment, health care, education and prevention. There have been no documented cases of rabies in vaccinated, truly immunized dogs and cats for two decades in the US, although the disease still exists among wildlife and feral companion animal species. While most pet dogs are vaccinated for rabies, fewer cats were historically vaccinated until laws required it.

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¹Dodds WJ. “Rabies virus protection issues and therapy”. Glob Vaccines and Immunol. 2016; 1(3):51-54. Doi:10.15761/GVI.100115.

²Dodds WJ. “Case Study: Rabies Vaccine Adverse Reaction in a Dog”. SL Vaccines Vaccin J. 2017; 1(1):111.

³Knobel DL, Arega S, Reininghaus B, Simpson GJG, et al. “Rabies vaccine is associated with decreased all-cause mortality in dogs”. Vaccine 2017; 35: 3844–3849.