2020 Rabies Vaccine Study – How Long Does the Shot REALLY Last???

When RCF began, Dr Jean Dodds said: 

 “From challenge trials, we know the DOI for regular vaccines is seven to nine years, if not longer. So why would the rabies vaccines, being so potent, not have an even longer DOI? We decided the thing to do would be to design a study to federal government standards that would determine if the DOI is longer than three years.” 

Reduce Adverse Effects of the Rabies Vaccine

Rabies vaccines cause a multitude of adverse effects. These range from immediate reactions to long term, chronic illness … and even death. 

Documented reactions include:

Countless animals suffer from these chronic issues. So, extending the legally required vaccine intervals would help reduce adverse rabies vaccine reactions. But it would still protect pets (and thus people) from rabies infection. 

RCF designed live rabies virus challenge studies to measure the long-term duration of immunity. They expected to show that duration of immunity of rabies vaccines is much longer than 3 years. 

Successful challenge studies (done according to USDA licensing code Title 9), could help convince State governments to allow longer intervals between rabies shots. RCF hoped to prove first 5 years immunity, and then 7 years. 

RCF also believed their studies might prompt vaccine manufacturers to come up with rabies vaccines licensed for 5 and 7 years.

Funding

Before the studies could start, RCF had to raise money. University of Wisconsin agreed to cover nearly half of the overhead for the study. But RCF still needed $177,000 for just the first year, and $150,000 each year after that.  

RCF was a true grassroots supported organization. Funding for the study came from many different sources … perhaps even from you! 

Everyone wanted the research to help change outdated and sometimes draconian rabies laws.

Many individual pet owners generously gave what they could afford to help fund the studies. Breed clubs, rescue groups, trainers, breeders, and kennel owners also donated to RCF. 

Roadblocks

The team ran into some unlucky obstacles along the way. 

First, finding a challenge facility to do the studies wasn’t easy. Typically, only vaccine manufacturers have large scale challenge facilities that are USDA approved. Dr Schultz found a facility for the challenges. But then the company was sold and RCF was left without a lab to do the challenges. 

Eventually they found a replacement facility. Dr Zhen Fang Fu of the Department of Pathology at the University of Georgia (UG) vet school agreed to run the challenge studies. But the lab could only accommodate 15 dogs at a time. 

So it took longer than planned to do the trials. 

Then … the USDA wouldn’t send the virus to any lab under biosafety level 3. UG’s lab was level 2. Luckily they were really keen to do the trials, so they upgraded the lab. 

But it caused another delay. 

Virus Failure

The third and biggest problem was that the live rabies virus used for the first challenge trial had lost its virulence. Only the USDA can supply the virus, so the researchers had to get a different virus for the remaining challenges. 

You’ll read in the description of Challenge Trial 1 how this major problem impacted the success of the studies.  

The Research

The study protocol followed the USDA’s Animal and Plant Health Inspection Service Title 9 CFR standards for licensing rabies vaccines. 

RCF ran two concurrent studies, for 5 and 7 years. 

They started with 100 female Beagle puppies. Ultimately there were 65 Beagles in the studies. 35 dogs were spayed and adopted out at the end of the studies. 

 There were 3 challenge groups. 

• At 12 and 15 weeks old, 3 groups of dogs got either a commercial rabies vaccine, or saline. 
• Challenge groups 1 and 2 had 15 dogs. Each group had 10 vaccinated dogs and 5 non-vaccinated control dogs.  
• Group 3 had 12 vaccinated dogs and 3 non-vaccinated control dogs. 

The two rabies vaccines were:

• Continuum Rabies (“Vaccine A”), by Intervet (Merck)
• IMRAB- TF (“Vaccine B”), a thimerosal-free vaccine by Merck.

A third rabies vaccine was used for the Revaccination Trial. I’ll explain that later.

The Rabies Challenge Trials

Before we talk about the results, here’s how the researchers did the challenge trials. 

“Challenge” means they injected live rabies virus into the dogs, under anesthesia. 

Then, every 8 hours for 28 days, they observed the dogs for signs of rabies, including:

• Hyper excitability
• Behavior changes
• Dilated pupils
• Photophobia (light sensitivity)
• Reduced appetite
• Inability to drink
• Vomiting
• Incoordination

If dogs showed any of these early signs of rabies, they immediately and humanely euthanized them. The dogs were never allowed to develop full-blown rabies. 

After the initial 28-day observation period, the researchers monitored survivors daily for the rest of the 90-day period.

The goal was to meet the USDA Code Of Federal Regulations (CFR) Title 9 … which require an 88% or higher survival rate. 

Challenge Trial # 1

The first challenge included 15 dogs:

• 5 unvaccinated control dogs
• 5 dogs vaccinated with Vaccine A, challenged 6 years 10 months after vaccination
• 5 dogs vaccinated with Vaccine B, challenged 5 years 5 months after vaccination

This challenge was “confounded” (unfortunately this means it failed!) … because of “insufficient virulence” of the challenge virus used. The virus came from the USDA … that’s the only way for researchers to obtain it. 

• None of the vaccinated dogs got rabies
• Only 2 of 5 unvaccinated dogs showed signs of rabies. 

The researchers are confident that if they’d had a sufficiently virulent virus, the trial would have met the USDA’s 88% survival requirement for rabies vaccination. 

But of course we don’t know that for sure.

The researchers obtained a different rabies challenge virus from the USDA for the remaining challenges.

Challenge Trial # 2

Challenge 2 was also done with 15 dogs.

• 5 unvaccinated control dogs.
• 5 dogs vaccinated with Vaccine A, challenged 8 years after.
• 5 dogs vaccinated with Vaccine B, challenged 6 years 7 months after.

In trial 2, all of the 5 unvaccinated dogs showed signs of rabies within 13 to 21 days of challenge.

This meant the rabies virus was sufficiently virulent this time. (They used the same one for Trial 3.) 

• Only 1 of 5 of the Vaccine A dogs showed protection against rabies (8 years after vaccination). 
• 4 of 5 Vaccine B dogs showed protection against rabies, 6 years 7 months after vaccination. 
• So … half of the 10 vaccinated dogs were protected. None of these 5 protected dogs developed clinical signs of rabies during the 90-day observation period. 

Challenge Trial # 3

For humane reasons the researchers reduced the number of unvaccinated dogs in this trial:

• 3 unvaccinated control dogs
• 12 dogs vaccinated with Vaccine B, challenged 7 years 1 month after vaccination.

To spare lives … only Vaccine B dogs were in Trial 3. That was because in Trial 2, the survival rate of Vaccine A dogs was only 20%. 

• Again, all unvaccinated dogs showed signs of rabies 14 to 21 days after the challenge. 
• 6 of 12 vaccinated dogs survived the 90-day observation period with no signs of rabies. 

Testing For Immune Response

As part of the challenge trials, the researchers also collected regular serum and lymph node mononuclear cell samples to test immune memory responses in the dogs. They analyzed: 

1. Serum samples using the RFFIT rabies titer test. 
2. Memory cell response by flow cytometry. 
3. Brain tissue for the presence of rabies virus using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). 

The purpose of this immune response testing was to establish a rabies antibody titer standard for protection against the disease. This standard doesn’t currently exist … although there is a standard for humans, under the CDC’s Advisory Committee on Immunization Practices (ACIP).

This would allow vets to confirm immune response by titer so they could be confident of rabies protection when writing exemptions for unhealthy dogs.  

This is especially important for seriously ill or immune-compromised dogs. Immune-compromised dogs are unlikely to mount an immune response, even if vaccinated. 

Test Results

• The study found that antibody responses (measured by titers) 12 days after the challenges correlated strongly with survival.
• Vaccinated dogs had significantly higher memory B-cells 4 days after challenge, compared to the unvaccinated dogs.
• All unvaccinated control dogs had virus in their brain tissues
• All vaccinated dogs who developed rabies had virus in their brain tissues.
• Vaccinated dogs who survived the 90-day post-challenge period had no rabies virus in their brain tissues.

Unfortunately, the study did not prove a protective rabies titer standard. 

This was disappointing … but didn’t really surprise the researchers. Dr Schultz had been taking titer data annually … so they’d seen how titers waned. 

It did show that B-cell immunity lasts even after titers drop below a titer level of 0.1 IU/ml. 

But the risk of rabies increases if titers fall below 0.5 IUI/ml. 

So, rabies boosters may still be “the prudent, safe decision,” according to prior studies. 

And unfortunately, for now, the law says those boosters have to be every 3 years. 

The researchers also did a revaccination trial. 

Revaccination Trial

10 dogs were revaccinated with Vaccine A, 6 years 1 month after their first vaccines. 

Another 10 previously unvaccinated dogs got either Vaccine A, or Vaccine C, PureVax Rabies by Merial. That’s the third vaccine I mentioned earlier. 

Vaccine C is a recombinant, non-adjuvanted feline rabies vaccine. 

• Recombinant means 2 viruses are spliced together.
• PureVax contains rabies recombinant canarypox virus, intended to stimulate a better immune response.) 

The researchers chose Vaccination C (off-label for dogs) for the Revaccination Trial because none of the dogs had had it previously. This would allow them to differentiate dogs with immune memory more easily than with Vaccine A. 

The other thing that’s significant about Vaccine C is that it has no adjuvants. This means it’s less likely to cause adverse reactions. 

There is no non-adjuvanted vaccine for dogs. 

Revaccination Results

• 90% of the previously vaccinated dogs had titers over 0.5 IU/ml …
• … Compared to only 30% of the previously unvaccinated (naïve) dogs
• The recombinant, non-adjuvanted vaccine (C), had much higher responses than the killed virus vaccine in the previously vaccinated dogs. 
• Vaccine C did not produce titers over 0.5 IU/ml in the naïve dogs.

The Revaccination Trial showed antibody response 6 years 1 month after initial vaccination was much higher than in the previously unvaccinated dogs.

In Conclusion …

The Rabies Challenge Fund has finished its work. The website states:

“We are no longer taking donations. Thank you for your support.”

But the trials did provide some hope for change in the future. 

Clearly the results were not what we’d all hoped. The rabies vaccination laws won’t be changing anytime soon.

But there are a couple of important details.

1. Many of us have believed that one rabies vaccination is enough to protect a dog for many years, possibly even for life. But the RCF studies did not prove that.

• The vaccinated dogs in the RCF studies all had two rabies vaccines (at 12 and 15 weeks of age). So the researchers weren’t trying to prove a “one and done” theory.
• Rabies vaccines, which used killed virus, don’t create as long a DOI as modified live vaccines (like parvovirus or distemper) do.

The study did show that fully vaccinated dogs who’ve had their first two initial rabies vaccinations should have solid protection for far longer than 3 years. 

So, for your own peace of mind … if you choose not to vaccinate your dog for rabies, you might want to get titers done. Then you won’t have to worry if your dog tangles with the local wildlife.

2. The studies were done to meet USDA standards for vaccine licensing,

• This means the dogs were injected directly with the rabies virus.
• That kind of challenge is quite different from your dog meeting a rabid raccoon in your backyard.
• It’s unlikely that any dog outside of a research facility would ever encounter the level of potent rabies challenge that the trial dogs did. 

The Revaccination Trial showed that, even if your dog’s rabies vaccine has expired … a booster should restore his protection. In fact, a few years ago, Kansas State University found the same thing in a rabies titer study they did.

So the recommendations for veterinarians in the 2016 Compendium of Animal Rabies Prevention and Control were updated. Since then, the guidelines say that if a dog exposed to rabies is overdue for his rabies vaccination, he can have a booster shot, followed by an observation period at home, instead of being euthanized or quarantined.

Does Your Dog Still Need A Rabies Vaccine?

The only way to know if your dog is protected from rabies is to have titer testing.  For now (if you want to obey the law) … you’ll still need to vaccinate your dog for rabies every 3 years in the US and most Canadian provinces. 

Unless you can get a vet to write you an exemption.

Vaccine exemptions are allowed in 18 US states (with a 19^th coming in May). 

You’ll need to find a vet who’s willing to give the exemption. Many conventional vets aren’t comfortable with exemptions. So, try to find a holistic vet who’ll be more likely to support your request. 

Even though most state legislation doesn’t allow rabies titers in lieu of vaccination … it’s a good idea to get a titer if you’re asking your vet for an exemption. 

To find out if your state provides exemptions CLICK HERE.

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Source:

Henriques, Julia. “[News] Rabies Challenge Fund Results.” Dogs Naturally, 20 Apr. 2020, www.dogsnaturallymagazine.com/rabies-vaccine-challenge-fund-results/.