New research studies intranasal vs. injectable vaccines

As we watch the first deliveries of the SARS-coronavirus 2 vaccines into the provinces, and the ongoing challenges with the distribution of vaccines, it is amazing to think about how quickly these vaccines came to market and how rapidly the scientists were able to accomplish the difficult Phase 3 clinical trials that are necessary to show the vaccines are effective and safe.

These clinical trials are usually fairly straightforward to understand although difficult to carry out. The researchers need to enrol eligible participants for the trial and in this case, the participants are randomized into two groups: one group receives the new vaccine and the other group receives a placebo injection.

The two groups are followed up over some period of time to see how many people in each group eventually might develop the symptoms of COVID-19. Anyone who develops any symptoms is tested to confirm the diagnosis.

In all of these trials, the researchers and the people receiving the vaccines are “blinded.” They don’t know which individuals received the vaccine and which received the placebo injection until the trial is finished.

If we want to compare the effectiveness of vaccines in cattle, the process is much the same.

A clinical field trial is the best scientific evidence for proving if a vaccine is effective.

Although we don’t have to find human volunteers, we still have lots of challenges, such as recruiting enough farms or enough animals to show a statistically meaningful result, following the animals after the vaccine treatments are administered to monitor the outcome and carrying out the trial in a setting where the disease is likely to occur, which allows us to see if the vaccine actually works.

These trials are expensive to carry out and are often challenging in real-life field situations. As a result, we don’t have lots of clinical trials done in the cow-calf sector.

Dr. Nathan Erickson and graduate student Adam Berenik along with colleagues at the Western College of Veterinary Medicine at the University of Saskatchewan recently published in the Canadian Veterinary Journal the results of a clinical field trial evaluating vaccination programs for beef calves.

The trial was carried out on a commercial cow-calf farm and followed up in a commercial feedlot. The researchers were comparing two different vaccine protocols.

Calves were randomized into two groups. One group of 322 calves received an injectable vaccine (Bovishield Gold FP 5; Zoetis Canada). This vaccine was administered in June on turn-out to pasture.

Another group of 319 calves received an intranasal vaccine (Inforce 3; Zoetis Canada) at the same time.

The calves were followed through to weaning and into the feedlot, where they all received the injectable vaccine as a booster on entry to the feedlot and where they evaluated the number of calves that were treated along with their average daily gain and if any calves died of respiratory disease during the trial.

It should be noted that this clinical trial is trying to evaluate a more complex clinical question. The researchers are trying to evaluate which of two vaccination programs is better. They are comparing a vaccination program where calves receive the same injectable vaccine at two time points (homologous program) to calves that receive an intranasal vaccine followed by an injectable vaccine (heterologous program).

This is far more difficult to show clinical differences than the trial that compares a vaccine to a placebo, which is the sort of question most of the SARS coronavirus 2 vaccine trials have focused on. Those trials are just trying to show if the vaccine is better than nothing.

The results of this trial could not show any significant differences in bovine respiratory disease morbidity, mortality and average daily gain between the two vaccination groups.

In the injectable group, nine percent of the calves were treated for bovine respiratory disease compared to 10 percent in the intranasal vaccine group. Average daily gain was identical when the two vaccination groups were compared. There were some differences in mortality levels, but they weren’t statistically significant, although there were some interesting trends.

The injectable vaccine group had a mortality rate of 0.3 percent while the intranasal vaccine group had a mortality rate of 1.6 percent. One calf died in the injectable vaccine group and five calves died in the intranasal vaccine group.

While this is interesting, it is not statistically significant. We can’t be sure if the deaths were due to the vaccination programs or simply due to chance.

To make things even more confusing, some of the other trials that have been published have shown results trending in the opposite direction. One previously published study showed that intranasal vaccines trended toward lower mortality.

These different results may be due to the level of disease challenge in the different clinical trial settings.

Unfortunately, this is how science works and the answers are not always evident after just one trial.

In the end, this clinical trial did not show a clear advantage to giving intranasal vaccines to calves versus giving injectable vaccines.

It looks like both programs are relatively equivalent and veterinarians will have to add this trial to the others to make a decision about which program would work best in different settings.

We do have other evidence from studies and other trials, and we know for certain that vaccinating calves is better than not vaccinating them.

However, we may not have the final answer as to which vaccine protocol provides the best protection in every situation.

Erickson and his team along with the funders of the research should be congratulated on attempting to carry out a clinical field trial on calf vaccination in a cow-calf herd. Clinical trials are the only way to get valid answers to many of the clinical questions we have about the effectiveness of vaccine programs and they are extremely difficult to carry out in the field. We need more of them in order to answer all of the questions we have.

John Campbell is a professor in the department of Large Animal Clinical Sciences at the University of Saskatchewan’s Western College of Veterinary Medicine

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