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A Tale of Two Vaccines

Two common childhood infections kill hundreds of thousands of children each year. St. Jude is creating vaccines to combat both croup and RSV.

Laniah Harris

Once tethered to life support because of an RSV infection, Laniah Harris is now a proud kindergarten graduate. St. Jude scientists are developing vaccines to prevent RSV and croup, so that no other child must endure what Laniah experienced.

When 5-year-old Laniah Harris began to cough and swipe at her nose one blustery February day in 2011, her mom, LaToya, pulled out a tissue. “Laniah must have caught a cold,” LaToya thought. But within 48 hours, the little girl was fighting for her life in the Intensive Care Unit.

Laniah had nearly completed leukemia treatment at St. Jude Children’s Research Hospital when she acquired the respiratory syncytial virus (RSV) infection. For most children, the infection is merely an annoyance, causing mild, cold-like symptoms. But for babies in the first year of life and children with cancer, the virus can spread to the lungs­ — often with deadly consequences.

Michael Meagher, PhD

Michael Meagher, PhD , vice president of Therapeutic Production and Quality and president of the Children’s GMP, LLC, leads the production phase of the vaccine project. St. Jude was the first pediatric health facility in the world to have on-site capability to manufacture highly specialized lifesaving products such as the hPIV1 and SeVRSV vaccines.

“RSV is really a nasty virus,” says Charles Russell, PhD, of St. Jude Infectious Diseases. “Within the first years of life, almost everyone has gotten infected with RSV, which causes at least 150,000 deaths a year.”

St. Jude researchers and clinicians want to shield all children from the dangers of RSV. That’s why scientists are developing vaccines to prevent RSV as well as croup. Caused by the human parainfluenza virus type 1 (hPIV1), croup causes a lung infection with a characteristic barking cough and can be dangerous in young toddlers. Infections by these two viruses kill hundreds of thousands of children each year. Currently, no vaccines exist to prevent infection; once a child is infected, the treatment is costly and often ineffective.

Elisabeth Adderson, MD, with Arthur Russell and his mother

Elisabeth Adderson, MD, of St. Jude Infectious Diseases visits with Arthur Russell and his mom, Mimi. Arthur participated in the croup vaccine clinical study. Although the SeVRSV vaccine is not ready for testing, scientists continue to recruit healthy children for the croup vaccine study.

The secret weapon

The secret weapon of the St. Jude vaccine project is a particle called the Sendai virus (SeV). The physical structure of this particle closely resembles that of hPIV1. Scientists use SeV as a decoy to fool the immune system into thinking it is being attacked by hPIV1. Immediately, the body’s B cells and T cells prepare a counter-attack. When the real virus later invades, the system is poised to destroy it.

Allen Portner, PhD, of St. Jude Infectious Diseases, began conducting basic research on SeV in 1968. Decades later, he met with Julia Hurwitz, PhD, of Infectious Diseases and other colleagues to discuss the possibility of using SeV as a croup vaccine. After years of lab work, the vaccine was ready for Phase I testing.

“Vaccine development is a slow, arduous process,” Portner explains. “From the day a vaccine is conceived in the laboratory until it reaches the pharmacy shelf to be dispensed is, on average, about 22 years.”

The late Jerry Shenep, MD, of St. Jude helped initiate the world’s first human study using SeV. The vaccine was successfully administered to adults at gradually increasing doses; the vaccine has also been tested in healthy children between the ages of 3 and 6. Elisabeth Adderson, MD, of St. Jude Infectious Diseases is now helping to advance the study. Phase I testing involves intensive attention to safety issues. The next two phases involve larger groups of participants. Eventually, scientists test the vaccine’s protective efficacy against infection as compared to a placebo.

And the results thus far?

“Indications are that the vaccine is completely safe,” Portner says.

Engineering a second vaccine

The existing St. Jude croup vaccine uses an unmodified laboratory strain of SeV. Creating an RSV vaccine using SeV, however, requires genetic engineering. A technique called reverse genetics has enabled researchers to modify SeV to piggyback the RSV F gene. By introducing that gene into the SeV carrier, scientists ensure that the immune system makes preparations to foil any future incursions by both RSV and hPIV1. The new vaccine, known as SeVRSV, has the potential to target both viruses at once.

Allen Portner, PhD; Charles Russell, PhD; Julia Hurwitz, PhD

Allen Portner, PhD (at left), Charles Russell, PhD, and Julia Hurwitz, PhD, of Infectious Diseases have been working on a project to create a new vaccine, known as SeVRSV. This vaccine will protect children against both RSV and hPIV1, which causes croup.

Russell is helping Hurwitz and Portner advance the SeVRSV vaccine. It is being produced in the Children’s GMP, LLC, an on-site facility that manufactures biologics and drugs under stringent federal regulations. Once the product has been manufactured to meet FDA specifications, Phase I safety testing of SeVRSV can begin. The project has already attracted interest from the National Institutes of Health (NIH) as well as from the pharmaceutical industry.

Prescription for success

Other research facilities worldwide have attempted to create vaccines against RSV, to no avail. Hurwitz cites several reasons why St. Jude may succeed where others have failed. First, the vaccine uses the SeV particle as its backbone, instead of the human RSV particle.

“Scientists elsewhere have taken RSV and tried to make it weaker—they culled it, adapted it or mutated it so that it wouldn’t cause disease in humans,” she says. “They’ve never been able to reach the fine balance you need to ensure both safety and efficacy.”

Another attribute of the SeVRSV vaccine is that it is administered through the nose, much like the FluMist® influenza vaccine. “You get a long-lasting immune response in the nose,” Hurwitz explains, “which blocks the virus at its point of entry. A single dose of this vaccine will induce long-term immunity, as opposed to some protein vaccines that require one or more booster immunizations.”

Finally, the new vaccine appears to be safe.

“We have every indication that SeVRSV will be extremely safe in humans, and so we have both safety and efficacy on our side,” she says. “Our approach seems to be on target.

“We want to see 100 percent immunogenicity, meaning that when unprotected children receive the SeVRSV vaccine, they will generate protective antibody responses against RSV and hPIV1,” she continues. “In the lab thus far, it has been 100 percent effective at inducing protective antibodies.”

Worldwide protection

Hurwitz, Russell and Portner believe that SeVRSV may hold the key to eradicating RSV and croup from the general population — thus protecting children like Laniah Harris from dangerous infections. After enduring a month on the ventilator, fighting for every breath, Laniah gradually improved. With the help of St. Jude staff, she relearned how to walk and began to regain her fine motor skills.

In May of 2012, Laniah took a deep breath and strode down the aisle at the St. Jude kindergarten graduation. As the 6-year-old bestowed an endearing, gap-toothed smile upon the cheering audience, her mom looked on with pride. Not only had Laniah completed cancer treatment and survived her harrowing bout with RSV, but she had also completed kindergarten.

From the vantage point of the beautiful young graduate — and for other children who may someday be able to avoid RSV altogether — the future is rosy, indeed.

Reprinted from Promise Winter 2013

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