Vaccines are key to controlling equine influenza virus

Since late 2019 we’ve been inundated with information about viruses, vaccines, and biosecurity practices and protocols such as masks, disinfection, and quarantine and isolation. What you might not realize is much of the information we have on SARS-CoV-2, the virus that causes COVID-19, can help us understand equine influenza virus (EIV) … and vice versa.

Both SARS-CoV-2 and EIV are highly infectious viruses associated with high morbidity but typically low mortality in otherwise healthy individuals. Many individuals can get sick when exposed to these viruses, but few succumb to disease. For example, the World Health Organization reported a mortality rate of about 2% for COVID as of late December 2021. In contrast, other viruses produce much higher fatality rates than EIV or COVID. Rabies is fatal in both humans and horses, and the equine mortality rate for African horse sickness ranges from 70% to 95%. Even West Nile virus is associated with higher mortality, at 35% and 10% in horses and humans, respectively.

Beyond Mortality

Though most horses aren’t perishing after contracting EIV, they can become quite ill. Common clinical signs include high fevers sometimes exceeding 104-106°F; a dry, hacking cough; and profuse clear nasal discharge. These are classic disease indicators, but in flu’s case they can lead to high vet bills and long recovery times. Horses typically need at least three weeks off from training.

“The standard rule of thumb is one week of stall rest for every day of fever,” says Tom Chambers, PhD, a professor and infectious disease researcher at the University of Kentucky’s Maxwell H. Gluck Equine Research Center, in Lexington. If complications such as secondary bacterial pleuropneumonia develop, however, horses can be out of commission for up to six months.

Then there’s the expense. Treatment costs aren’t typically prohibitive unless severe complications occur. Most horses recover uneventfully with time and supportive care. But the effects of missed training and competition time can reach far beyond farms’ lost business. The horse industry supports agriculture, forestry, hotels/motels, commercial sports, real estate, and wholesale trade. The competition sector alone contributes an estimated $28.3 billion annually to the GDP and supports more than 400,000 jobs (Huseman et al. 2021).

The Lowdown on Lockdowns

Not all flu cases result in widespread quarantines and lockdowns. Just like humans with COVID, individual horses can hunker down at home and isolate until after the infectious phase of the disease has passed and the horse has recovered.

“It is the severe outbreaks affecting larger numbers of horses that typically necessitate an official quarantine,” says Chambers. “Usually, the veterinarian in charge of, let’s say, a racetrack, after diagnosing the first few cases of flu in an outbreak, will work directly with the state veterinarian to determine the next steps in disease control for that group of horses.”

To understand the power of quarantine, let’s look at the most famous equine flu outbreak in recent history: Australia 2007. This event stemmed from horses imported from Japan. Australia had historically been EIV-free and, to remain that way, had a post-import quarantine system in place. The horses stayed in quarantine, but the virus escaped and  ultimately infected 70,000 horses on more than 9,000 properties. While the data trace back to one shipment of vaccinated horses, testing during the tracing process showed those horses had little to no protective antibodies against EIV. This suggests the horses responded poorly to vaccination, the vaccines were ineffective, or owner compliance with recommended protocols was poor. Officials waged a huge five-month-long campaign to stamp out EIV, and the country was declared EIV-free again in 2008 to the tune of more than AU$1 billion (US$700,000,000). Veterinarians and officials eradicated EIV from Australia using strict quarantines, restricted horse movement, disease control “zones,” decontamination measures, and increased surveillance and ­vaccination.

“Australia went to great lengths to restrict horse movements and, frankly, I was surprised they were able to eradicate the disease, especially considering the feral horse population that might have become a reservoir for the virus,” says Chambers.

Unusual EIV Activity

According to OIE (the World Organization for Animal Health) data from 2006-2017, “all inhabited continents had at least one country with an EIV outbreak.”

More recently, however, 2015-2019, especially 2018-2019, were unusually active times for EIV globally:

• Outbreaks in Africa in 2019 were detected in Cameroon, Mali, Niger, Nigeria, Senegal and Sudan;
• In the U.S., outbreaks were reported each month in 2018 and 2019 across 33 states; and
• An extensive outbreak in Europe affected at least 228 premises, including approximately 100 premises in the U.K., 56 in Ireland, and more than 60 in France beginning in 2018. 

“The outbreak in Europe affected all sectors, and both vaccinated and unvaccinated horses were affected,” the OIE stated in a bulletin. “However, protection was much better among vaccinated horses compared to unvaccinated horses, and horses correctly vaccinated over several years often showed no clinical signs or were only mildly affected.”

Roles and Goals of Vaccination

Keeping up with the latest clades, strains, and mutations of flu viruses and SARS-CoV-2 is tough. Some of the concerns about vaccination relate to vaccines protecting against circulating viruses. For example, will the original COVID vaccines protect people against developing mutations? Similarly, will horses’ immune systems recognize the next EIV strain as a version of the virus they were vaccinated against previously? If not, then aren’t vaccinated humans and horses at risk? Not necessarily, but that’s why we must study viruses causing outbreaks, says Chambers. His motto: There are no guarantees.

“The immune system and immune responses are not an all or nothing thing,” he says. “The virus is constantly evolving (via antigenic drift), trying to stay one step ahead of the host’s immune system. But the immune system also evolves. The horse isn’t protected one day and unprotected the next.” Antibody recognition of a pathogen gradually decays.

“A sudden change is called antigenic shift, in which the flu virus proteins change to a new form so dramatically that the circulating antibodies don’t recognize the antigen anymore, but for EIV that hasn’t happened since 1963,” he adds.

Chambers says when experts mention “short-lived immunity,” they’re referring to circulating antibody levels in the blood. 

“We can easily measure serum antibodies to get a general assessment of the horse’s immune response,” he explains. “We expect that following vaccination, antibodies against that virus will spike then gradually fall off. This is especially the case in younger horses.”

Those serum antibody levels decline because of the normal turnover of proteins inside animals; they don’t last forever.

“The immune system is designed to be turned on and off,” Chambers says. “When it doesn’t need the antibodies anymore, when it isn’t actively fighting that specific infection, then … antibody levels decay. Over time, those antibodies are pulled out of circulation and destroyed.” 

In fact, it isn’t healthy for the horse’s immune system to be in a constant state of emergency. The immune system, says Chambers, is essentially destructive in nature. If it were “on” all the time, it would cause a great deal of collateral damage.

He explains that one key to successful immunity is training the immune system to make antibody-producing cells called memory B cells that allow it to “turn on” and respond quickly in the event of an infection. 

The problem with the natural antibody decline is that a trough in protection levels develops before the next vaccination. At that time it’s possible for the horse to become infected. Typically, these horses only have mild clinical signs, such as a day or two of cough, fever, and runny nose—not nearly as severe as if an unvaccinated horse were infected, but still more illness than most horse owners would like to see.

Frequent vaccination boosts antibody levels and reduces chances of illness. The more frequently your vet gives boosters, the higher the levels of protective antibody titers. To avoid EIV at important times, work with your vet to map out your vaccinations and boost at appropriate intervals. For more on vaccinating against flu, review the American Association of Equine Practitioners’ Vaccination Guidelines: https://bit.ly/3eKnMwT.

Chambers emphasizes that the goal of the flu vaccine is to dampen clinical signs, not avoid illness altogether. Vaccination also does not prevent reinfection. This can help owners set more reasonable expectations regarding what a vaccine can and cannot do.

Updating Flu Vaccines

Chambers says immune protection isn’t black and white but, rather, a spectrum.

“An EIV-exposed horse may appear healthy but still be virus-positive by PCR testing,” he says. “For the horse’s immune system that counts as a win, but for the owner trying to import his horse into Australia it counts as a loss. For this reason, it is necessary that the EIV vaccines should work as well as possible against a virus that has a simple but very effective strategy to defeat them … antigenic drift.” 

For the future, researchers hope manufacturers can make a flu vaccine that works against all strains. Until then, ­vaccines contain a small number of strains (two for EIV) and work best against similar circulating strains (i.e., causing outbreaks).

“Antigenic drift eventually makes these flu vaccines obsolete,” Chambers says. “How long this process takes is highly variable. To try to determine whether EIV vaccine strains are sufficiently similar to the EIV strains causing outbreaks, an international panel of specialists, under the auspices of the OIE, does ongoing studies of outbreak strains collected from around the world.” Chambers is on this panel.

Surveillance studies of virus isolates from horses naturally infected with flu allow the panel to analyze the amino acid sequences of viral antigens (i.e., the H and N proteins) to determine if mutation is expected to affect the vaccine-trained immune system’s ability to recognize the virus. Using these, the OIE determines if currently licensed vaccines must be updated to provide maximal protection to horses against strains causing outbreaks.

Based on the OIE’s latest recommendations (last published in April 2020 and reviewed again in July 2021), “There is no evidence-based scientific justification for revising the current recommendations on vaccine composition.” That is, the strains currently causing outbreaks, including all the outbreaks worldwide in 2019, are still highly similar to the strains in vaccines as far as the immune system is concerned. 

Eventually, this won’t be true anymore, and the vaccines will need updating, says Chambers. “But according to all our tests, we aren’t there yet—which, I have to admit, was not my prediction 10 years ago.”

The OIE panel recommends EIV vaccines contain strains representing both clades 1 and 2 of the H3N8 EIV Florida sublineage. It says old EIV strains including H7N7 virus or an H3N8 virus of the Eurasian lineage are not necessary, as they seem to be extinct.

The OIE makes annual vaccine update recommendations, but it’s the manufacturers’ responsibility to produce, test, and gain license for updated vaccines that follow those recommendations. The U.S. government does not require updates, though satisfying OIE recommendations is a factor when new vaccines come up for licensure. Once one is licensed, it can remain on the market indefinitely.

“All the leading vaccine manufacturers are aware of the strain recommendations,” says Chambers. “Updating a vaccine is not a trivial job. The best way for a horse owner to get information about EIV vaccines is to talk to their veterinarian. The best way for veterinarians to know what strains of the flu are included in a particular vaccine and whether it has been updated is to read the company’s literature or talk to a representative.” 

Take-Home Message

The COVID-19 pandemic provided opportunities for horse owners to better understand how quickly infectious respiratory viruses can spread and the ­consequences—expanding their grasp of equine influenza and other viruses. It is crucial to reduce horses’ risk of infection using vaccination, even in the face of viral mutations. Even though no vaccine is 100% effective, when used with appropriate biosecurity protocols, even virulent respiratory viruses can be maintained at low levels within animal populations.