Vaccine pipeline looks bright for 2006

March 2006

MIAMI BEACH, Fla. — The world of pediatric vaccines is changing all the time. Within the next year alone, there may be as many as three new vaccines approved.

Lance E. Rodewald, MD, director of the immunization services division of the CDC, gave a brief rundown here at the Miami Children’s Hospital 41st Annual Pediatric Postgraduate Course, “Perspectives in Pediatrics,” of all the vaccines that have been added to the immunization schedule in the last year, as well as a few that may be soon be added.

“The value of vaccines is very easy to forget because we don’t see these diseases as much as we used to due to the success of vaccination programs,” Rodewald said. However, his years as a practicing physician have afforded him a profound appreciation for the progress against diseases that vaccines have made. And, he added, judging by the recent number of vaccine approvals, it does not appear that progress against disease will slow anytime soon.

“We’re entering an unprecedented time. Between a year ago and a year from now, there will be five new pediatric vaccines,” Rodewald said.

Recently approved vaccines

The first of these, the meningococcal conjugate vaccine (MCV4; Menactra, Sanofi Pasteur), was approved in January 2005. This vaccine has come under some scrutiny following five reports to the CDC’s Vaccine Adverse Event Reporting System of Guillain-Barré syndrome (GBS) within a few weeks of receiving MCV4. However, Rodewald said, as of Feb. 9, 2006, some 3 million doses of the vaccine were distributed, and only seven cases had been seen. As of that date, there were no changes in the vaccine recommendation. He said the number of cases of GBS so far appear to be no greater than what would be expected due to chance.

The two tetanus–diphtheria–acellular pertussis vaccines (Tdap) – GlaxoSmithKline’s Boostrix and Sanofi Pasteur’s Adacel — are part of what Rodewald termed a “new war” against pertussis. Adacel is available for adolescents and adults aged 11 to 64. Boostrix is indicated for adolescents and teenagers aged 11 to 18.

While pertussis vaccination levels among infants aged 19 to 35 months have in recent years become the highest ever recorded, cases have been rising in adolescents and adults. As such, health officials added the adolescent vaccines to the immunization schedule last year, and last month, the Advisory Committee on Immunization Practices (ACIP) was expected to discuss the issue of vaccinating health care workers and older adults against pertussis.

“The primary objective [of this strategy] is to protect children against disease, but the secondary objective is to reduce the Bordetella pertussis reservoir, and potentially reduce the incidence of disease in other age groups,” Rodewald said.

A single dose of the Tdap vaccines, according to Rodewald, is recommended for adolescents 11 to 12 years of age instead of Td. According to the ACIP recommendation, teenagers aged 13 to 18 who have not received Tdap should receive a single dose of Tdap as their catch-up booster instead of Td. Rodewald said many pediatricians have asked whether they can defer Td until they get the Tdap vaccines into their practice, and he said this may be done if the last dose of tetanus-containing vaccine was administered within the last 10 years, and the child does not need immediate protection from tetanus.

The combination measles-mumps-rubella-varicella vaccine (MMRV; ProQuad, Merck), was approved in September 2005 for use in children 12 months through 12 years of age. Rodewald said the attenuated measles-mumps-rubella vaccine viruses in ProQuad are identical and of equal titer to those in the measles-mumps-rubella (MMR) vaccine, MMRII (Merck). However, he said, the titer of Oka/Merck varicella-zoster virus is higher in MMRV vaccine than in the single antigen varicella vaccine, Varivax (Merck). The advantage of the MMRV vaccine, according to Rodewald, is that it can decrease the number of injections received by children when all of the component antigens are indicated for administration.

In the pipeline

Several vaccines will likely get added to the routine immunization schedule this year as well.

The first of these, Merck’s rotavirus vaccine, Rotateq, was approved last month. In early January, there were two studies published in The New England Journal of Medicine on both the Rotateq vaccine, and GlaxoSmithKline’s rotavirus vaccine candidate, Rotarix. The two products differ somewhat, in that the Merck vaccine is a bovine-human reassortant vaccine and GSK’s product is an attenuated human vaccine.

Merck’s product is orally administered in a three-dose schedule. According to the study results, which looked at 70,301 participants, the vaccine decreased trips to the hospital emergency room by 94% and trips to the clinic by 86%. The intussusception rate, which had been elevated in association with the last licensed rotavirus vaccine, was the same between the Rotateq and placebo groups, according to the study.

Another Merck vaccine (Gardasil), which has been submitted to the FDA for licensure, will hopefully make a dent in the human papillomavirus (HPV) rate. He noted data that looked at college women over a four-year period. Although women at enrollment had no evidence of infection, by the end of the study, about 50% had become infected. In the United States, there are about 2.8 million abnormal pap tests, more than 10,000 cases of cervical cancer and about 1 million cases of genial warts per year, according to Rodewald. An effective HPV vaccine would hopefully reduce the incidence of all these, he said.

Two HPV vaccines are on the horizon, Merck’s product, which covers strains 6, 11, 16 and 18, and GlaxoSmithKline’s candidate, Cervarix, which covers types 16 and 18.

Merck announced in October that Gardasil in clinical trials was 100% effective in preventing infection with HPV strains 16 and 18, which together cause about 70% of cervical cancer cases. Cervarix, which is further back in development than the Merck product, has also been shown to be 100% effective in preventing HPV strains 16 and 18 in early clinical trials.

“Biotechnology advances are providing important new tools to fight more infectious diseases,” Rodewald concluded. “There will be challenges to implement these vaccines, but the payoff is going to be well worth the effort.”

For more information:

• Rodewald LE. The future of vaccine development and safety. Presented at: Miami Children’s Hospital’s 41st Annual Pediatric Postgraduate Course: “Perspectives in Pediatrics”; Feb. 6-9. 2006; Miami Beach, Fla.