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Vol. LX, No. 7
April 4, 2008
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Virus Smart, Science Smarter
New Viral Vaccines in ‘Great Teachers’ Spotlight

On the front page...

In 1796, when Edward Jenner scratched cowpox vaccine into the arm of a human subject, he changed the history of public health. Cowpox boosted immunity to smallpox, one of the world’s most deadly and horrific contagions. Thanks to Jenner’s work, continued by Pasteur, vaccines would become an essential part of modern medicine. By 1980, smallpox was eradicated worldwide.

NIH furthers that heritage by supporting vaccine research and medical education, as in the recent Great Teachers lecture “New Viral Vaccines: The Shingles and the Human Papillomavirus Vaccines.”

Continued...


  Dr. Anne Gershon discusses shingles, HPV vaccines.  
  Dr. Anne Gershon discusses shingles, HPV vaccines.  

“Tell us what it felt like [to suffer from shingles],” said Dr. Anne Gershon, professor of pediatrics, Columbia University College of Physicians and Surgeons. She was speaking to Dennis Morrissey, whom she welcomed as an NIH vaccine trial volunteer. Then, in the classic tradition of Grand Rounds, she seated Morrissey alongside her at the base of Lipsett Amphitheater.

Shingles is a sequela—that is, a secondary, subsequent disease—of chickenpox. Shingles presents as an exquisitely painful, blistery rash, typically on one side of the body.

“My eye was involved, so it was upsetting,” said Morrissey, a retiree. “It felt like having a severe sunburn, then walking into a spider web.” A mild breeze against his face was so painful he abandoned hobbies such as bird-watching as well as exercising at the gym; even drawing became impossible. “I couldn’t concentrate,” he said.

The culprit was a virus that causes two diseases. First, the childhood illness chickenpox (known as varicella). Even after chickenpox resolves, the virus doesn’t leave the body; it becomes latent in nerve tissue. At some point, it can escape from latency and reactivate as disease 2: shingles (known as zoster). Outbreaks of shingles can occur many years, even decades, after the childhood bout of chickenpox has resolved.

There are 1 million zoster cases annually in the United States, said Gershon. It tends to affect adults over 50. While not every case of chickenpox results in shingles, up to half of adults who live to age 85 will get it.

“Acute zoster affects activities of daily living,” Gershon added. Those afflicted report pain, depression, reduced social functioning and psychological impairment. Complications include scarring, reduced sensation and even paralysis.

“I got the vaccine,” said Morrissey, “and eventually I got zoster anyway.” No vaccine is 100 percent protective, said Gershon. In the Shingles Prevention Study, about 35 percent of vaccinees in Morrissey’s age group developed zoster with resultant pain, despite the vaccination. It is still possible that Morrissey was at least partially protected by the vaccine from the effects of shingles.

Some, like Morrissey, suffer from post-herpetic neuralgia (PHN)—pain persisting after the shingles lesions have healed. Both incidence and persistence of PHN increase with age. Morrissey’s PHN lasted for 2 years, he said.

In the Shingles Prevention Study, “the vaccine prevented zoster in the elderly,” she said. Its effectiveness varies depending on age, but it’s almost 65 percent effective in adults ages 60-69. For those in their seventies, it’s 55 percent effective.

The vaccine also reduces PHN. Composed of a live, attenuated (disabled) virus, the vaccine is safe, Gershon noted. It can be given to prevent chickenpox, and, since it increases “cell-mediated immunity,” it can also be used therapeutically to prevent zoster in persons with latent infection with the varicella-zoster virus. It’s recommended for use in those over 60, who are not immunocompromised.

In the second portion of the hour, Gershon lectured solo, without featuring a study volunteer.

The human papillomavirus (HPV), she said, is the most commonly transmitted of sexually transmitted diseases (STDs) in the U.S. By age 50, more than 80 percent of American women test positive for at least one strain of HPV.

There are many different kinds of HPV, said Gershon, calling them “very clever viruses” that can cause cervical cancer, genital warts and laryngeal papillomas (warts in the larynx, or voice box) in infants. Scientists have identified 19 high-risk HPV strains.

Eunice Kennedy Shriver speaks at Mar. 3 ceremony in her honor.
Gershon provided explanations of two new vaccines gaining attention: one for shingles and the other for HPV.

“The HPV vaccine is preventive, not therapeutic,” said Gershon. That’s still excellent news. The virus causes cervical dysplasia, a precursor to cervical cancer. And once cervical cancer becomes invasive, it’s a killer of women. Prevention is key.

“Young girls are susceptible” to HPV, said Gershon, “because of the immaturity of the cervix… the infection is [typically] acquired soon after sexual debut and many girls and young women become persistently infected.”

The licensed vaccine targets the two most common HPV types, strains 16 and 18, which cause around 70 percent of all cervical cancer. Both the safety and efficacy of the HPV vaccine, Gershon said, have been proven in clinical trials.

“The virus is smart,” she explained, “but virologists here at NIH turn out to be smarter, because they figured out a way to vaccinate against an oncogenic [cancer-causing] virus.”

The vaccine is composed of virus-like particles containing the HPV “capsid proteins” from its viral shell. An aluminum adjuvant (preservative) adds to the vaccine’s safety by inhibiting bacterial contaminants. And this point is important: “The antibody titers [post-vaccination] were much higher than after natural infection,” Gershon said.

In a landmark study, there was 100 percent efficacy in preventing external lesions and adenoma in situ (invasive cervical cancer).

“There are still questions,” Gershon noted. While the vaccine is currently deemed safe, there are no long-term safety data yet.

“Who should be immunized? Here is the controversy,” said Gershon. Vaccine administration should occur before individuals become sexually active, she said, and that includes both males and females. Both can carry the virus.

If we wait until after young people become sexually active, said Gershon, “we can screen [female patients] with Pap smears [Papanicolaou smears—tests to detect cervical changes] april 4, 2008 vol. lX, no. 7but we will still have women die from cervical cancer...The vaccine has no effect if people are already infected—unlike the zoster vaccine, the HPV vaccine is only preventive, not therapeutic.

“When I was a young pediatrician,” she continued, “we didn’t learn about STDs in kids because we didn’t think they had them.” She said that 11- and 12-year-olds should be immunized for HPV when they get their routine Hep-B, meningitis and booster DPT injections. “Just give them all together,” she said. This is what the American Academy of Pediatrics has recommended.

“My granddaughter, at 11, she’ll get [the shot],” said Gershon. “It isn’t a big deal for these girls, in spite of what you read. We need to protect everybody.”

And, she added, most people think that, eventually, boys should get the vaccine too. The safety of the vaccine is currently being studied in boys in clinical trials. NIHRecord Icon

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