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Intranasal vaccines get around maternal antibodies

Animal Health: Maternal antibodies unpredictable

Intranasal vaccines get around maternal antibodies

Calves are born without fully functioning immune systems, making them reliant on passive immunity from maternal antibodies for disease protection.

As a result, we assumed for a long time that vaccinating calves at an early age was a complete waste of time and money as the maternal antibodies would attack any pathogens introduced in the vaccine.

Today, explained Dr. Philip Griebel in a recent talk to the University of Calgary veterinary medicine’s beef cattle conference, we know how to get around those maternal antibodies and give the calf’s immature immune system a little more protection against disease.

Griebel, a veterinarian and research fellow with the Vaccine and Infectious Disease Organization — International Vaccine Centre (VIDO-Intervac) at the University of Saskatchewan, fast-forwarded through a decade of research on calfhood vaccination strategies carried out by his team and at the University of Guelph.

The measure of immune response to a vaccine has always been increased levels of antibodies in the blood specific to the pathogens introduced by the vaccine. When scientists started looking at immune response from other angles, they discovered that even though maternal antibodies inhibit most of the modified live virus (MLV) in intramuscular (IM) vaccines, some T-cells did respond. T-cells are the first line of defence because their initial job is to recognize foreign invaders and set the chain of immune response in action. And the T-cells responded even better after a second vaccine given two to three months later.

Building on this work, others began looking at killed bacterin vaccines given during the first two months of life. With the immature immune system there was a low response, but never enough to protect the calf from a disease challenge.

“Producers would still not be getting a lot of value, so we started asking if we could deal with the problem of maternal antibody interference by changing the route of vaccine delivery to a mucosal surface,” he says. Mucosal surfaces are special epithelial surfaces in the lining of the nose, intestinal tract and reproductive tract that produce a type of antibody called IgA.

Maternal antibodies that circulate in the bloodstream are a type called IgG. One of VIDO-Intervac’s first studies showed that maternal IgG transfers very well to blood serum, but did not get across the epithelial barrier to enter the nose. The small amount of maternal IgA transferred to the calf disappeared within three days of birth because it was secreted in the mucous produced in the nose.

Use of an MLV intranasal (IN) vaccine to protect against respiratory disease failed to have any effect on circulating IgG levels, but all was not lost. Nasal secretions showed calves that received the MLV IN vaccine at birth started to produce their own IgA in nasal secretions within 10 to 12 days, whereas all of the maternal IgA disappeared from nasal secretions of calves that hadn’t received the vaccine.

"All we have to do is change the site of delivery by about a foot from the neck to the nose."
"All we have to do is change the site of delivery by about a foot from the neck to the nose." photo: Supplied

“So the mucosal immune system is functional in these newborn calves,” Griebel says. “We can access it despite early high levels of maternal antibody transfer and we can get very good levels of antibody produced there. We saw that within five to six weeks after vaccination, the IgA starts to wane but a second vaccination at that time gave an even greater (IgA) antibody response.”

Maternal antibodies unpredictable

One reason is that the quantity, quality and timing of colostrum beef calves receive varies considerably. Maternal antibodies are transferred through colostrum but can only be absorbed through the calf’s gut into its bloodstream within the first hours of life. There’s no way in an everyday ranch setting to be sure of the level of maternal antibodies, the specific diseases those antibodies target, or the duration of the passive immunity.

Field trials were carried out in co-operation with a rancher from southern Sask­atchewan. The cows were vaccinated with a five-component MLV IM vaccine given three to six weeks before breeding to find out whether the levels of maternal antibodies transferred to the calves the following spring would be sufficient to block infections. Blood was drawn from 90 calves before vaccinating at branding when the calves were three to six weeks old.

Griebel says maternal antibody levels were incredibly high for BVD (bovine viral diarrhea) type 1 and type 2, very high for PI-3 (parainfluenza), but low for BHV-1 (bovine herpes virus) and BRSV (bovine respiratory syncitial virus). Testing again at weaning in October when the calves were six to seven months old showed that some had low levels of maternal antibodies against both BVD types, but upwards of 80 per cent of the calves no longer had immunity to any of the other viruses.

The level of maternal antibodies declines by about 50 per cent every three weeks. Projecting that out, Griebel calculates that if calves suckled lots of colostrum high in antibodies, the level of protection would be low by three to four months of age. Calves that didn’t receive much colostrum or colostrum with low levels of antibody could have little protection remaining by one month of age.

“So, we really don’t know when we should be starting to vaccinate,” he says.

Immune memory a powerful tool

“Using a vaccine to put in place immune memory is a very valuable way of enhancing disease protection in your herd. If we use immune memory in our vaccination program, we can get protective immunity in place within three to four days as compared to giving a vaccine for the first time, when it could take three to four weeks before protective immunity is achieved,” Griebel explains.

Results from the study of the 90 ranch calves illustrates this point. Half of them received a dose of MLV IN vaccine and the other half received a dose of water in the nose at branding. At weaning, blood samples showed that none of the calves had any remaining maternal IgG antibodies.

A week later, 20 of the calves from each group of 45 were pulled off the cows and transported to the research facility in Sask­atoon. Half of the 20 vaccinated calves received a booster with the same IN vaccine the day after they arrived and the other 10 were not revaccinated. The 20 calves that had not been vaccinated at branding were also split into two groups: 10 received their first dose of MLV IN vaccine and 10 were not vaccinated.

This gave them four study groups: never vaccinated, vaccinated only at weaning, vaccinated only at branding, and vaccinated at branding with a booster at weaning. All calves were infected four days later with a high dose of IBR (infectious bovine rhinotracheitis) virus. Fever was the measure of the onset of clinical disease and weight loss was an indicator of the severity of the infection.

The never-vaccinated calves developed high fevers within two to three days and the high fevers were sustained through day seven. Relative to the day of challenge, these calves lost almost 10 per cent of their body weight, or 40 to 45 pounds.

The calves vaccinated once at branding had lower fevers that came down sooner and they lost less weight than the calves in the never-vaccinated group, but the differences were not statistically significant.

It was the same story for the calves vaccinated once at weaning. The vaccination appeared to be of benefit, but the differences weren’t statistically significant.

Fever was completely eliminated in the calves that had been vaccinated at branding and again at weaning. These calves maintained their weight through the seven days post-weaning, despite undergoing the same stresses of abrupt weaning, transport to a new environment and diet change topped off with the disease challenge.

The twice-vaccinated calves were also the only ones with very little virus shedding. This was measured in all groups because it indicates the usefulness of a vaccine strategy in providing protection at the herd level. Sick animals shed copious amounts of virus, thereby adding to the environmental load and increasing the risk of disease transmission to herdmates. If the infection level is high enough it will overcome protection provided by vaccinating, Griebel adds.

In another IBR-challenge study, groups of calves were vaccinated once or twice with either a killed IM vaccine, MLV IM vaccine, MLV IN vaccine, or saline solution. Control calves shed more than one million virus particles per millilitre of nasal secretion for up to 10 days after infection.

The killed vaccine didn’t reduce the incidence of clinical disease (fever) nor the level of virus shedding. The MLV IM vaccine eliminated most of the clinical disease, but had very little effect on the level of shedding. The MLV IN vaccine eliminated fever and reduced shedding to 10 virus particles per millilitre of nasal secretion and there were no virus particles in the nasal secretions after six days.

The surprise finding, says Griebel, was 60 per cent of the never-vaccinated calves died of secondary bacterial pneumonias within the seven days following infection.

“This shows how important stress is because, if we take unvaccinated, weaned calves that have been in our facility for a month or two and then infect them with IBR, they get sick and recover very well. If we take abrupt-weaned calves, transport them and infect them, 60 per cent develop fatal secondary bacterial pneumonias. Management is important because a relatively severe disease can turn into a fatal disease,” he stresses.

Vaccination is important because none of the calves in any of the other groups developed a fatal pneumonia.

“All we have to do is change the site of delivery by about one foot, from the neck to the nose, and we can completely circumvent the problem of maternal antibody interference,” he says.

Options for calfhood vaccinations

Often producers think of using vaccines when it’s convenient even if handling cattle one extra time could save problems in the long run. His challenge to producers is to think about how you could integrate the vaccination program for cows with a much better vaccination program for calves to set them up for their entire lives and get immunity in place for weaning.

Consider the pros and cons of the following strategies:

  1. A single MLV IN vaccine given at three to six weeks of age provided some persistence of immune memory. It significantly reduced deaths, but didn’t have much effect on clinical disease when challenged with the same viral respiratory infection at the time of weaning.
  2. A MLV IN vaccination given at weaning without a primary MLV IN vaccine at branding significantly reduced clinical disease, mortality and virus shedding. From a herd health perspective, this gives the biggest bang for the buck.
  3. A MLV IN vaccination at branding, boosted with the same vaccine at weaning achieved rapid onset of immunity within four days with a high level of protection during the high-stress weaning period.
  4. A single MLV vaccination, whether IN or IM, given three weeks before weaning reduced post-weaning respiratory disease and, therefore, virus shedding. This protection is as strong as vaccinating at branding and again at weaning.
  5. An MLV IM vaccination at branding with a booster of the same vaccine at weaning did not improve disease protection compared to a single injection of MLV vaccine for the first time at weaning. There is no significant benefit from giving a MLV IM vaccine at branding if you are going to give a MLV IM vaccination at weaning.

Quick sorting

University of Calgary veterinary researcher Dr. Philip Griebel says a common barrier to delivering vaccines at the most appropriate time is the hassle involved in sorting the calves from the cows. Here, he gives a big shout-out to his colleague in the Western College of Veterinary Medicine, animal behaviour, welfare and beef specialist Dr. Joseph Stookey, who published a YouTube video on an efficient way to very quickly get the job done without stressing animals and handlers. Stookey and his team got the idea from Alberta rancher Dylan Biggs when they were researching low-stress weaning options.

Pairs are gathered into one corral where they instinctively move to the opposite end and then turn around to wander back toward the gate, where they find an open alley leading to a second corral. Adjacent to the entrance to the alley is a panel with the bottom two bars removed so the calves can duck under and into a separate corral. A person standing at the entry to the alley controls the flow by taking a small step back to allow cows to drift into the alley or a small step forward as a calf approaches. Calves are more leery of people, so a small step toward the alley entrance is enough to send them scooting under the panel to keep them following along beside the cows in the adjoining alley.

The easiest way to find his videos on easy sorting and two-stage weaning is to search for Joseph Stookey on YouTube.

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