As a bird hunter in Oregon, Scott Linden often takes his hunting dog, Buddy, into the heart of rattlesnake habitats. While the German wirehaired pointer has never been bitten, the Bend-based host of the Wingshooting USA television series takes no chances and protects his hunting companion with a rattlesnake vaccine that’s been on the market for more than 15 years.

But with little scientific research on the efficacy of the vaccine, he’s taking it on faith that the vaccine works.

“Many of the hunters that have dogs that have been bit by rattlesnakes would swear by the fact that the damage to their dog was lessened by the vaccine,” Linden said.

That’s made the rattlesnake vaccine a controversial topic in veterinary circles. Laboratory tests show the vaccine offers some protection against rattlesnake venom in mice, but there have been no published research studies showing its effectiveness in dogs or horses.

“There’s a huge debate on that,” said Dr. Adam Stone, a veterinarian with the Bend Veterinary Specialty and Emergency Hospital. “I think almost every doctor that you talk to is going to have a bit of a different opinion.”

The vaccine is manufactured by Woodland, California-based Hygieia Biological Laboratories and distributed by its sister-company Red Rock Biologics. It’s the brainchild of veterinarian Dale Wallis and her partner, whose cats were bitten by rattlesnakes in California and nearly died. They scoured the veterinary journals to read up on the work Wyeth Laboratories did to develop an antivenom treatment for rattlesnake bites of people in 1953.

Antivenom is made by injecting horses or sheep with gradually increasing amounts of rattlesnake venom.

The animal then builds up antibodies that can neutralize the venom. Those antibodies are then given to patients after a bite. A vaccine works in a similar way, creating antibodies to the venom, so they’re already in place if a bite occurs.

Wallis says Wyeth used four types of snake venom to create an antivenom that would work against three quarters of rattlesnake venoms.

For its vaccine, Red Rock opted to focus on just one venom, from the western diamondback rattlesnake, which would provide the greatest coverage for the types of rattlesnakes found in the westernUnited States.

Wallace and her partner experimented with various ways to inactivate the venom that would still allow it to generate an immune response. The process is similar to the tetanus vaccine, which protects against a toxin produced by a bacteria. The toxin is separated from the bacteria and rendered nontoxic. The immune system recognizes that inactivated toxin and creates antibodies against its original form. That was the road map they needed.

“People have been trying to make snake vaccines for a hundred years, and nobody has been successful,” Wallis said. “This is the first commercial vaccine that’s available for animals.”

They conducted tests in mice and vaccinated their own dogs. An Orland, California, kennel, whose border collies were getting bitten as they herded sheep, allowed them to vaccinate their dogs. Blood samples from the collies showed the vaccine led to the creation of antibodies, and serum taken from those dogs neutralized rattlesnake venom in test tubes. That was enough to convince the State of California to license the vaccine in 2003.

But in 2010, California shut down its state office regulating biologics, and oversight of the canine vaccine, and a equine vaccine licensed in 2008, shifted to the USDA. USDA granted a conditional approval of the vaccine after Red Rock submitted purity, safety and potency data.

“Efficacy is the one that’s holding us up a bit,” Wallis said. “We’ve done lots and lots of … trials in mice, but it’s a lot harder to deliberately envenomate a dog.”

She said USDA has been pushing the company to do a study where they inject both vaccinated and unvaccinated dogs with rattlesnake venom, and compare the results. But the company has resisted doing that.

“If we do a study in beagles, does it apply to Labradors?” Wallis said. “I don’t want to have to do this. Thirty dogs per breed, and what, 30 breeds? That’s a whole lot of pain and suffering I don’t feel is warranted at all.”

A compromise approach may be to do tests with low levels of venom in vaccinated and unvaccinated dogs, and then look at markers of inflammation and tissue damage in laboratory tests.

“I think ideally what you would do is try to get a dose that is not lethal and also not so tissue-toxic that it results in a lot of pain for the animal but enough so that you could pick up some of the inflammatory markers,” said Dr. Lyndi Gilliam, a veterinarian with the Oklahoma State University Center for Veterinary Health Sciences. “Nobody wants to have a control group if you’re going to do a venom challenge. You just can’t.”

That’s left veterinarians unsure of whether to recommend the vaccine. Neither the American Animal Hospital Association nor the American Association of Equine Practitioners have strong recommendations backing the vaccine. Only a handful of journal articles even address the vaccine, and none gives more than a clue about its efficacy. The challenge faced by Red Rock is that there are just too many variables associated with snake bites in animals.

In one of the few controlled experiments, researchers at the University of California-Los Angeles vaccinated 45 mice and then injected them with venom from the western diamondback, the northern Pacific or the southern Pacific rattlesnakes. Six of 15 mice survived the western diamondback venom, and three of 15 survived the northern Pacific venom. The southern Pacific venom killed all 15 mice.

Studies of the vaccine in dogs have primarily been reviews of medical records from dogs who have been bitten, not experiments where researchers controlled all the variables. For example, veterinarians in Arizona reviewed records from 272 dogs bitten by rattlesnakes between 2010 and 2012. Only 15 of the dogs had been vaccinated, and the researchers could not identify any measurable benefit from the vaccine.

But the study and another with similar results included only a small number of vaccinated dogs and only dogs who were brought to an animal hospital. It’s possible vaccinated dogs experience fewer problems after being bitten and so owners do not seek medical treatment. It was also unclear from the records when the dogs were vaccinated and whether they had received any boosters.

Even with larger numbers, studies would have to sort out the impact of dogs of different sizes exposed to different amounts of venom from different subspecies of snakes at various durations after being vaccinated.

“Every single bite is a unique experience,” Wallis says. “It’s really hard to generalize.”

Red Rock has considered whether to create a rattlesnake vaccine for humans using a similar process, but the high costs of human trials and the limited demand for the vaccine make than unfeasible. The company has learned that some snake handlers have vaccinated themselves, but the company expresses warns against that.

Wallis also stresses that just because a dog has been vaccinated, doesn’t mean they won’t need treatment.

“Where we’ve lost dogs is when the owners waited,” Wallis said. “Your best medicine in the case of a snake bite is your car keys.”

Stone said many dogs need vial after vial of expensive antivenom after a potent bite. About 25 percent of bites are dry bites where no venom is injected and a third are mild bites. The remainder are more severe with large amounts of venom.

A single dose of the vaccine costs in the range of $25 to $50, and dogs need a second dose three to six weeks later. The level of antibodies wanes over time, so veterinarians recommend an annual booster shot before the typical season when rattlesnakes are most active, in late spring and summer in Central Oregon. Antivenom treatment, on the other hand, can run into the thousands of dollars. The vaccine, Stone said, could impart a level of protection equal to one or two vials of the antivenom.

Most veterinarians also agree there is little downside to vaccinating.

“We always have to think about risk versus benefit, and if the animal is in a high-risk areas, and for sure if they’re in an area with western diamondbacks, I think it’s kind of a no-brainer,” Gilliam said. “If it’s an area where the animal is not going to be at high risk, then I may weigh it a little bit more carefully.”

Linden agrees. He cautions that the vaccine might not work equally well against all types of rattlesnakes, but there may still be some benefit with little risk.

“It won’t hurt,” he wrote in a recent blog entry, “and it could help.”

—Reporter: 541-633-2162, mhawryluk@bendbulletin.com