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Hormel Institute professor and Cryo-EM Director Susan Hafenstein, PhD and Carol Bator, Cryo-EM project specialist, have co-authored a paper entitled “Cryo-EM structures map a post-vaccination polyclonal antibody response to canine parvovirus,” which was recently published in Communications Biology.

The paper describes the findings of a study analyzing how certain antibodies responded to canine parvovirus (CPV) after vaccination in dogs.

To better understand the host’s immune response to vaccination, researchers obtained sera from two different dogs vaccinated against CPV eight and 12 weeks post-vaccination. Sera, plural for serum, is a component of the blood that plays an important role in immune function.

Polyclonal antibodies from the sera were then purified and cryo-electron microscopy (cryo-EM) was used to capture high-resolution renderings of the structures of the polyclonal Fab-virus complexes to study how effectively antibodies could compete with the CPV virus. Polyclonal antibodies are a mixed group of multiple types of antibodies released from B cells that can identify and bind to multiple areas of the same antigen. A “Fab” region, short for “fragment antigen-binding,” refers to the area of an antibody that binds to antigens to defeat and remove them from the body.

Researchers also used custom software to analyze the polyclonal Fab-virus complexes. Ultimately, a total of five distinct antibodies between the two dogs were identified, all of which were found to reliably prevent receptor binding, thus protecting the host from infection.

The study helps to affirm that accomplishing such complicated mapping using subparticles is indeed possible, and similar approaches could potentially be applied to study other viruses.

“Usually we can only solve the structure of one monoclonal antibody at a time. Using a special approach where we break down the virus capsid [its shell] into subparticles, we were able to map the polyclonal response of the dog,” Hafenstein said. “Typically, we have to spend a lot of time and effort to select single monoclonal antibodies from an immune response. Here, we took everything and mapped them to the capsid.”

Also unique was that the dogs’ immune responses seemed highly focused initially, with just two or three select types of responding antibodies in each dog being identified. However, regardless of why that may be, all five antibodies identified were consistently effective in binding to the virus capsid to defeat it.

CPV arose in the 1970s as a variant of a virus related to feline panleukopenia virus (FPV), which occurs in cats. This extremely contagious and potentially fatal virus’s mutation led to a pandemic among dogs starting in 1978, as the paper notes.

In infected dogs, CPV weakens the immune system and eventually makes its way to the small intestine’s epithelium, which is the lining that helps absorb nutrients and acts as a barrier to protect against fluid loss and keeps gut bacteria contained from the rest of the body.

In addition to domesticated dogs, CPV has also been detected in other species, including wild animals such as raccoons, foxes, and coyotes. Thanks to the development of vaccines, vaccinated dogs today are much better protected from CPV; dog owners are likely familiar with their pet’s routine “parvo” shots at the veterinarian’s office.

Hafenstein noted that while CPV affects mostly canines, understanding more about the virus and animals’ immune responses to it also has potential implications for human health.

“It’s a canine parvovirus. So it’s not about humans, but it is about humans, because this virus jumps species,” Hafenstein said, adding that this makes understanding the virus’s mechanisms — and finding ways to keep it in check — all the more important.