La Jolla Institute for Allergy & Immunology Awarded Grant to Test Safety of New Smallpox Treatment

SAN DIEGO — The La Jolla Institute for Allergy & Immunology (LIAI) has received a $7.1 million grant from the National Institutes of Health (NIH) to fund safety and effectiveness testing of an antibody treatment that quickly fights the smallpox virus.  The treatment could be the nation's first line of defense in protecting against a terrorist-originated smallpox outbreak and may eventually be stockpiled nationwide alongside the smallpox vaccine. 

"This work is particularly important because those younger than 36 years old in the U.S. population have not been vaccinated against smallpox, which makes the need for a strong and fast-acting treatment all the more vital should we ever face a smallpox outbreak," said Mitchell Kronenberg, PhD, LIAI president and scientific director. 

LIAI scientist Shane Crotty, PhD, who developed the antibody treatment, said the NIH grant will fund pre-clinical testing of the work he and his research team started three years ago.  In 2005, the researchers, studying blood samples from people who had received the smallpox vaccine, were able to isolate the anti-H3 antibody as an extremely potent fighter against smallpox. The scientists then proved its effectiveness by testing in mice.  

The NIH was intrigued by the work and asked Crotty to further develop the antibody treatment for use in humans.  "Now we've made fully human antibodies to fight the smallpox virus," said Crotty.  The collaborative research team led by Crotty developed the human antibodies using technology which allows human antibodies to be developed from special genetically engineered mice. 

"You have to have fully human antibodies to use this treatment as a human therapeutic," explained Crotty.  If further testing shows the treatment to be safe and effective in humans, Crotty said the NIH has indicated interest in stockpiling the antibody nationwide.  "Hopefully we will never need to use it, but if we do, the treatment will be there." 

Crotty said further testing of the human antibody for safety and efficacy will be conducted using highly sophisticated animal models. "We can't actually do these experiments in humans because it would be extremely dangerous and absurd to purposefully expose people to the smallpox virus," he said, noting that no live smallpox virus will be used in any of the studies.  "We will use experimental animal systems that can show that this antibody would work in humans without actually testing it on infected humans."  Crotty said the anti-H3 human antibody has already proven to be effective in animal testing protocols that the FDA used to license the only currently existing smallpox treatment.

"In that model, our antibody worked much better at treating smallpox than the currently licensed therapy," he said.  The existing therapy provides only modest protection and is difficult to make because it must be purified from the blood of people who have recently had the smallpox vaccine.  "This is another reason our treatment is so appealing," Crotty said.  "Not only does the anti-H3 antibody provide better protection, but it can easily be produced in very large quantities for stockpiling."

The smallpox virus has been the subject of intense research interest worldwide in the last several years, prompted by bioterrorism concerns.  The virus was mostly eradicated in the U.S. early in the 20th century and vaccinations for the general public were ended in 1972.  But in the aftermath of 9-11, new concerns have arisen that the smallpox virus could be used as a bioterrorist agent.  Disease experts fear that samples of the smallpox virus may have fallen into the hands of terrorists or dangerous countries at some point.  This concern has led to the creation of worldwide stockpiles of the smallpox vaccine over the last several years. 

"While we do have a smallpox vaccine, there are concerns because people who are immuno-compromised, including infants and the aged, cannot use the current vaccine," Kronenberg said.  It is estimated that as much as 10 percent of the U.S. population should not receive the vaccine. 

Additionally, if there were a smallpox outbreak, there would be a certain time lapse before people could receive the vaccine.  "In general, vaccines are preventive," said Crotty.  "You must receive the vaccine before you are infected or sick.  Otherwise, it won't do you any good." 

However, unlike the vaccine, the anti-H3 antibody would provide immediate treatment, even if the person had already been exposed. "It would work similar to how an antibiotic treats and for a short time protects against a bacterial infection," said Kronenberg.  "This could be very important should people become infected before they have a chance to be vaccinated."

Source: La Jolla Institute for Allergy and Immunology