Rabies Challenge Study Results Are In–What Do They Mean?

The subject of vaccination is one of the most common, and sadly most controversial topics I address on this blog. As I have said many times, vaccines have both risks and benefits, and the balance between these must be assessed in the context of the risk of specific diseases, the scientific evidence concerning specific vaccines, and the health and needs of individual patients. The available evidence is overwhelming that vaccines do far more good than harm for most pets, and following the most recent, evidence-based guidelines is almost always the right choice for most pets.

However, fears of vaccines that are out of proportion to the real risks are widespread, and unfortunately there are some veterinarians who encourage such fears. These doctors rely mostly on anecdote to support their anti-vaccine claims, but some do cite scientific evidence (accurately or, more often, inaccurately) to make their case. Some critics of standard vaccine practices even attempt to produce their own research evidence to support their approach. This research frequently has flaws or limitations which make it not particularly reliable or illuminating. 

One example I have discussed in the past is a study by Dr. Jean Dodds, a noted proponent of various kinds of pseudoscience, from raw diets to unreliable lab tests. She published a study challenging common vaccine practice in 2016 in the Journal of the American Holistic Veterinary Medicine Association (JAHVMA), a niche journal dedicated to pseudoscience. This study purported to show that small dogs could be fully immunized, and would have fewer adverse effects from vaccines, if given half of the usual 1mL quantity of most vaccines. In reality, the study was of such poor quality that it showed nothing of the kind and really provided no useful information, merely the illusion of evidence to support Dr. Dodds’ personal beliefs.

Dr. Dodds has now published another vaccine study, in concert with a couple of academic vaccine researchers and a lay person who advocates for limiting vaccination because she believes her personal dog developed cancer because of a vaccine. This study has received a lot of press coverage, associated largely with efforts to raise money to fund it and with advocacy efforts to restrict rabies vaccination. It has been in progress since 2008, and the results have been eagerly awaited not only by vaccine critics but by vaccination proponents such as myself hoping for some useful evidence to help guide our rabies vaccine practices. Unfortunately, once again the study has limitations that render the results of very little use.

Dodds WJ, Larson LJ, Christine KL, Schultz RD. Duration of immunity after rabies vaccination in dogs: The Rabies Challenge Fund research study. Can J Vet Res. 2020;84(2):153-158.

The stated purpose of this study was to demonstrate that the duration of protection from rabies vaccination is far longer than the three years most vaccines are proven to be effective and to provide support for changing legal rabies vaccination requirements and common veterinary practices. While there are potential risks to rabies vaccination, as for all effective medical therapies, these are rarely common or serious, and there is yet no real evidence that extending the interval beyond three years will reduce the risks meaningfully without also increasing the risk of rabies for some dogs. 

Nevertheless, it is always useful to get additional high-quality research evidence to help guide clinical practice, so this study could have been useful. From a logistical and ethical perspective, studies looking at the effectiveness of rabies vaccine are difficult because you have to expose some dogs to certain death and others to the risk of death from this fatal disease in order to test the protection offered by vaccines. That was done in this study, but it ended up adding only very little useful information to discussions of rabies vaccination practices.

The study initially included 100 dogs, a huge number by veterinary standards. However, 35 of the dogs were not used at all, and only 35 were part of the challenge study directly testing the duration of protection provided by rabies vaccination. These were divided into several groups given different vaccines and tested for protection at different times.

Vaccine A
This was killed, adjuvanted vaccine of the type commonly used for dogs (though the specific vaccine is no longer manufactured). Dogs were vaccinated at 12 weeks of age and again at 15 weeks of age. This is not a standard or recommended protocol used commonly in practice. Most dogs are vaccinated once at 12-16 weeks of age and then given a booster one year later, so this does not really reflect common practice. Presumably this was done because the dogs needed two vaccinations to be fully immunized, and the authors did not want to wait 1 year to give the booster and then have the challenge stage of the trial delayed by that year.

At 6 years and 10 months after the initial vaccination, the vaccinated dogs were exposed to rabies, as were 5 unvaccinated dogs in the control group. The USDA standard for proving a rabies vaccine good enough for use is that it must porrect at least 88% of vaccinated dogs. In this trial, all 5 dogs survived the challenge. However, only 2/5 control dogs developed rabies, showing that the virus used for the test was not sufficiently active (natural rabies infection kills 100% of infected animals). Therefore, these results can’t tell us if the test dogs were truly protected at this time point.

At 8 years after final vaccination, another challenge was done with 5 vaccinated and 5 unvaccinated dogs. This time, all of the unvaccinated dogs died, showing the test virus was active. However, all but one (4/5 or 80%) of the vaccinated dogs also died, so at this time the vaccinated dogs were no longer adequately protected. 

The investigators also looked at whether or not vaccinated dogs could generate an appropriate antibody response to a booster vaccine given 6 years and 1 month after initial vaccination. None of the dogs had an antibody titer considered protective at this time (and neither did the unvaccinated dogs, of course). A booster of the same type of vaccine generated a protective antibody level by 14 days after the booster I 90% of the vaccinated dogs (and 30% of the unvaccinated controls). The authors also gave some dogs a booster using a recombinant rabies vaccine made for cats, and though this would not be done in actual practice, this also generated a protective antibody response in most dogs.

Vaccine B
The authors also vaccinated several groups of dogs with another rabies vaccines, this one marketed as not containing the preservative thimerosol. This reflects Dr. Dodds antivaccine biases, since vaccine opponents often claim that thimerosol is a dangerous toxin despite the fact that it has been used extensively and shown to be safe in humans and animals for decades. This vaccine is not widely used, though apart from the missing preservative it is equivalent to common rabies vaccines.

Of the dogs vaccinated at 12 weeks and again at 15 weeks with Vaccine B, 5 were included in the initial challenge study at 5 years in which all vaccinated dogs survived but so did 60% of the unvaccinated dogs. Another 5 from this group were challenged at 6 years and 7 months after final vaccination, of which 4/5 (80%) survived. Another 12 of these dogs were challenged with rabies at 7 years and 1 month, of which 6/12 (50%) survived.

What Does It All Mean?
Unfortunately, the answer is, “Not much.” The study used two rabies vaccines that are not in common use and an initial vaccination protocol that differs significantly from standard practice, so it’s not the best model for studying how rabies vaccination usually works. The numbers in each challenge group were quite small, and the death or survival of a single animal could drastically change the apparent percentage surviving or dying the challenge, so any broad generalization about the dog population in general would be unsupportable.

The first challenge studies at about 5 and 6 years can’t be interpreted since most of the unvaccinated dogs survived the virus challenge. Even though all of the vaccinated dogs lived, this doesn’t prove that we should be given rabies vaccines every 5 or 6 years instead of every 3 years. This might be an effective interval for many dogs, and there are some other sources of evidence that suggest rabies vaccine protection might often last longer than 3 years, but we still can’t say this with any confidence. Given the very severe consequences of being wrong, namely the death of many dogs and potentially of people exposed by these dogs, and the lack of evidence that extending the interval by a few years would have any meaningful benefits, this portion of the study doesn’t really provide a reason to change current recommendations.

Of the dogs challenged at about 6 ½ years, 20 percent of them died, which is more than the allowable 10-12% under the USDA guidelines, and certainly more than we should thjnk of as acceptable. In this study, that 20% was only 1/5 dogs, but in a population of millions of pet dogs vaccinated every year, that could represent a huge risk to both our pets and the human population. 

This is reinforced by the portion of the study looking at antibody titers, since none of the 10 dogs tested 6 years after vaccination had a titer above the established protective level. This suggests we would be wise not to wait as long as 6 years before given rabies boosters to our dogs. Similarly, of the dogs challenged at 7 years, 50% died, so we certainly shouldn’t think of this as an acceptable interval between vaccinations. 

All in all, this study undermines the claims some vaccine critics make that a single rabies vaccination is all dogs should ever need. In fact, it reinforces concerns that extending the interval between vaccines will put more dogs at risk from rabies and do more harm than good. Even if 4-5 years between boosters is as effective as 3 years, it is very unlikely this change would have any significant benefits given that the risks of rabies vaccination is very low, and considerably less than most vaccine critics suggest. An interval of 6 years or more looks very likely to increase the risk of rabies significantly based on this study. 

Some vaccination critics are already suggesting that even though this study didn’t turn out the way they wanted, it still supports their general argument that we should vaccine less often than 3 years and use titers instead of vaccination. However, in the published study the authors are careful to point out that the results do not establish that a given titer level is sufficient to prove a dog is protected nor that any specific interval beyond 3 years is safe, even though they still believe this is true. 

Even though I believe the risks of current rabies vaccination practices are often exaggerated, I am disappointed that the time and effort put into this study, and the dogs sacrificed as part of it, did not provide useful evidence to clarify the overall duration of immunity provided by standard vaccination practices. I also hope the authors will be vigorous in challenging the use of their work to argue for changes in rabies vaccine laws or common practice since the data do not support such changes even if the authors personally believe they are warranted.