Hutch researchers discover neutralizing antibodies to parainfluenza

The new report is the result of several years of studies aimed at detecting protective antibodies against the Parainfluenza virus from human blood and tissue samples. The first potent antibody, which the scientists call PI3-EI2, was isolated from a donor’s blood in an extensive laboratory process developed by Taylor’s team. Initially, they identified 25 different antibodies that bound to the parainfluenza virus, but later faltered to just one that showed promise to neutralize it.

They later used a high-throughput process developed by their Hutch colleague, Dr. Andrew McGuire, to search for more candidates and expand their search to tonsils and spleen tissues rich in antibody-producing blood cells called B cells. They came with four more antibodies, each as potent or more potent than the first against parainfluenza.

“We found that tonsils in particular were packed with B cells that neutralized the virus,” said Boonyaratanakornkit.

Coincidentally, recent research has shown that adults who have had tonsillectomies as a child – a very common procedure in baby boomers – have a higher long-term risk of respiratory infections. Once one of the most common surgical procedures, tonsillectomies fell out of favor in the 1970s, as doctors cited a lack of evidence that they were beneficial.

To confirm that antibodies against the parainfluenza virus can also block it in mammals, the researchers tested that first powerful antibody in cotton rats, rodents that – unlike mice – are sensitive to parainfluenza. Rats given an injection of the antibody and challenged with a pinch of HPIV3 a day later were protected against significant lung infection.

The original goal of Taylor and Boonyaratanakorkit’s research is to see if lab-produced copies of these potent antibodies – known as monoclonal antibodies – can be formulated into a drug that can be injected into transplant patients to prevent or control parainfluenza to treat.

An anti-monoclonal antibody drug, palivizumab, is used to treat severe cases of respiratory syncytial virus or RSV, a common and sometimes dangerous childhood respiratory virus that also threatens immunocompromised patients. Encouragingly, the researchers found that the parainfluenza antibody’s ability to suppress that virus was better than palivizumab’s ability to suppress RSV. Although the drugs and diseases are different, the strategy for fighting the viruses is similar.

Boonyaratanakornkit is taking the lead in the next phase of this research within Taylor’s lab. Ultimately, the goal is to discover and develop a range of powerful antibodies against various viral diseases that threaten immunocompromised patients. These could be formulated into a single “cocktail” that can be administered or injected into transplant patients to prevent or treat opportunistic infections that take advantage of their impaired immune status.

“The list of infections to which they are susceptible is quite well known, and for most viral infections there are no preventive or therapeutic options,” said Taylor. “We hope to change that in the coming years.

“We started with HPIV3, but our goal in the coming years is to have tools to prevent or treat several other infections.”

A pioneer in the new field of B cell engineering, Taylor is developing ways to genetically modify a patient’s own B cells to produce antibodies of choice so that a person can generate these protective proteins themselves without the need for a vaccine or repeated infusions of expensive monoclonal antibodies.

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