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3 Open Minutes with Rodrigo Bicalho

Progressive Dairyman Editor Walt Cooley Published on 23 May 2014

rodrigo bicalho

Dr. Rodrigo Bicalho of Cornell University’s College of Veterinary Medicine recently published promising new research indicating the possibility for a future vaccine that would be effective at preventing metritis. Progressive Dairyman Editor Walt Cooley interviewed him about the research.




What is the mystery surrounding metritis that your research helped to answer?

BICALHO: There are many different questions still open about metritis, such as, “Why do some cows develop the disease and others don’t?”

There are many risk factors associated with the disease that are usually associated with immune suppression around parturition. Those are all still unknowns.

Our research addressed the dogma that metritis could not be prevented with vaccination. That assumption came from the fact that there are many bacterial pathogens associated with metritis. People thought that designing a vaccine to address all these different pathogens would be impossible.


I think our biggest contribution with this research so far is that we show pretty convincingly it is possible to design an effective vaccine. I think this is definitely a breakthrough because most people did not believe this would be possible.


Tell me how you conducted your most recent research.

BICALHO: For the last six years, the bulk of the research we conducted was actually studying the microbiology of the uterus. We’re thankful to have many dairy farmers in upstate New York and around Ithaca who allowed us to have access to their cows in order to collect samples and bring those samples back to the laboratory here at Cornell.

We’ve performed intricate, detailed molecular work on the pathogens we have found in the uterus. We compared the pathogens we found from cows affected with metritis with the same bacteria we found from cows that were not affected.

Then we did molecular epidemiology studies, in which we go in and we map a bacteria’s genome and study the virulence factors, which are the genes that are expressed when a pathogenic bacteria infects the uterus allowing the bacteria to cause the disease. All of that research was conducted with collaboration from dairy farmers; without it our research would have been impossible to complete.


Once we understood the microbiology, we produced a test vaccine in our laboratories, and we vaccinated animals on collaborating dairy farms. We evaluated the results and reported them in an article titled “Subcutaneous Immunization with Inactivated Bacterial Components and Purified Protein of Escherichia coli, Fusobacterium necrophorum and Trueperella pyogenes Prevents Puerperal Metritis in Holstein Dairy Cows” in the PLOS One journal in March.


What did you find in your research about these vaccines?

BICALHO: There’s two important bullet points. First, systemic subcutaneous vaccination using a combination of antigens grouped in three different vaccines decreased the incidence of postpartum metritis by up to 83 percent.

Second, vaginal vaccination – which we initially thought would be a good idea because it might stimulate the mucosa of the reproductive tract – did not work. Vaginal vaccination did not protect against metritis pathogens and did not decrease the incidence of metritis.

We now know the subcutaneous vaccination produces massive amounts of an immune response, meaning IgG production against metritis antigens in the postpartum uterus.

The uterus is very permeable to all blood components that will leak in to make the involution of the uterus possible and to also defend the uterus against pathogens. We’re pretty convinced that the further research route to pursue is toward a subcutaneous vaccination, which is probably more practical anyway.


In the simplest terms, how does the vaccine work?

BICALHO: This is a question we can only partially answer, even in complex terms.

When we tested the combination of antigens we used in our research, which targeted specific proteins and bacterins, the systemic response against the vaccine resulted in a systemic protection against the disease.

Now, we don’t know exactly if it is acting only by decreasing the pathogen level inside the uterus, or only by creating tolerance to the toxins and the LPS that is produced inside the uterus that causes systemic disease, or by decreasing the invasiveness of the pathogens, or a combination of all of these.

These questions will be the subjects for future research so we can fully comprehend how the vaccine is working. It’s most likely a combination of all these factors since the vaccine is a multivalent vaccine that targets many different areas of the disease.


This vaccine has been described as a ‘complex cocktail’ of metritis-causing pathogens. Explain what that means.

BICALHO: So in the vaccine we used, we targeted three different pathogens, and we used two different strategies to target them. One strategy was to use two isolates of each pathogen as a whole-cell vaccine. We have probably one of the largest collections of metritis-causing pathogens in the world. We used two of the most virulent pathogens we have found in our collection, inactivated them and incorporated them into the vaccine.

Our other strategy was to produce certain proteins from these pathogens, purify them and enrich the whole-cell vaccines with these proteins. These proteins are known to be pivotal in the process of metritis infection. The vaccines had up to nine different components.


This research was done on first-calf heifers. How might the results be different in older cows?

The incidence of metritis is higher in first-calf heifers. The reason why we choose first-calf heifers is because, as a group, they are more homogenous than cows are. They have less variation in body condition score and age. First-calf heifers have a lot more puerperal metritis, up to twice more than cows.

On the other hand, metritis has a much larger impact on cows’ performance. They will lose more milk, experience more of a negative effect on their reproductive performance and survive the disease less often. We believe the beneficiary factor of using a vaccine in cows can be bigger because of the implicit impact of metritis on infected cows.


What is the timeframe for commercialization of this vaccine?

BICALHO: It’s probably going to take at least a couple of years for this vaccine to be on the market.


What are some of the things the scientific community still needs to learn about metritis?

BICALHO: Until recently, people thought the immune system of the cow was the only relevant component of metritis, and the microbes were not that important. Our research, and research by others, has demonstrated that microbes are indeed very important in preventing the disease.

We do know the cows that go on to have metritis have their immune system compromised. They’re not immunologically functioning to their best. But we don’t know why that’s happening.

Also, one of the most important pathogens associated with metritis is P. pyogenes. We were the first ones to sequence its genome.

Even though human pathogens for the most part have all been sequenced, the relevant cow microbes are still out there to be studied. There’s a lot to learn still. PD

walt cooley

Walt Cooley
Progressive Dairyman