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Date: October 18, 1995
For Release: 6 pm EDT
Contact: NIH/NICHD (301) 496-5133

The study, which appeared in the October 19 issue of The New England Journal of Medicine, also shows that the vaccine was highly safe and significantly reduced the severity of the disease in those patients who become infected despite vaccination. Of great importance is the fact that none of the recipients of the pertussis toxoid vaccine developed serious side effects. Results of the trial were first announced by NICHD in November, 1994. Today's article provides the first detailed account of the trial's findings.

The new vaccine is based upon the theoretical work of the late Dr. Margaret Pittman at the U.S. Food and Drug Administration. It was developed by Ronald Sekura, PhD, formerly of NICHD, and John Robbins, MD, Chief of NICHD's Laboratory of Developmental a nd Molecular Immunity, and their colleagues.

Pertussis is a severe disease marked by periodic coughing spasms (paroxysms), that typically persist for more than 6 weeks. Rapid inhalation of air following a severe coughing spasm causes the victim to make a whooping noise. The disease may result in seizures, pneumonia, encephalopathy (a life-threatening swelling of the brain), and death.

In 1933, before routine immunization with diphtheria-pertussis- tetanus vaccine, there were more than 250,000 cases of pertussis in the United States with over 5,000 deaths. At present, about 85 percent of U.S. children receive their full course of pertussis vaccines. There are from 3,000 to 7,000 cases of pertussis in the U.S. each year, with from 10 to 15 deaths.

The NICHD acellular pertussis (aP) vaccine consists of a single component, pertussis toxoid. The toxoid is modified pertussis toxin, a protein produced by the bacteria that causes whooping cough, Bordetella pertussis. The toxin is treated with hydrogen peroxide, which inactivates it so that it induces protective immunity without causing disease symptoms.

The aP vaccine, along with diphtheria and tetanus toxoids, was given in a randomized, double-blind, placebo controlled trial, to 1724 Swedish infants at 3, 5, and 12 months of age. A control group of 1726 children received a vaccine containing diphtheria and tetanus toxoids alone. The children were observed for about 3 years.

In all, 312 children developed pertussis that met the World Health Organization criteria for the disease--21 days of paroxysmal cough plus a positive culture for pertussis or significant pertussis antibody production. Of these, 72 had received the new vaccine, and 240 had received the control vaccine, producing a protective efficacy rate of 71 percent. The severity of illness of the children who developed pertussis was also lessened in the aP group.

Moreover, the new vaccine caused no serious side effects. The side effects of the whole cell vaccine currently in use in this country--fever and local swelling and, in rare cases, seizures--have made many parents reluctant to have their children immunized against this dangerous disease. Rarely, a shock-like state may also occur after administration of the whole cell vaccine. In addition, based upon antibody studies, the NICHD aP vaccine can be expected to yield a longer duration of immunity than the current vaccine.

The combined aP, diphtheria, and tetanus (DTaP) vaccine was manufactured for the NICHD trial by AMVAX, a subsidiary of North American Vaccine, Inc., which holds the license from NICHD for its production.

The trial was undertaken in Sweden, where pertussis has been endemic since the 1970s, when concerns about the safety and potency of the whole cell vaccines resulted in low vaccine acceptance. Since 1979, pertussis vaccination has not been recommended in Sweden and there is no licensed pertussis vaccine available in that country. Most children in Sweden have had pertussis by age 10. Accordingly, it was ethical to have a control group not vaccinated with pertussis in clinical trials performed in Sweden.

"In conclusion, a pertussis-toxoid vaccine was safe and immunogenic and reduced the incidence and severity of pertussis," the investigators wrote. "We propose that pertussis toxoid is both safe and sufficient for the vaccination of children and adults."

Pertussis may also occur in older children and adults, usually in a less severe form that frequently is indistinguishable from other respiratory illnesses. Only infants and small children are given the current whole cell vaccines, as the pertussis vaccine may evoke severe localized reactions in adults and older children. However, because infected adults may also infect infants, an acellular pertussis vaccine for adults would be desirable.

In the United States, the schedule for routine childhood vaccination calls for five doses of pertussis vaccine, three in the first year of life and two thereafter. The fourth dose is given at 12 to 18 months of age and the fifth is given before school entry at 4 to 6 years of age. Whole-cell pertussis vaccine is currently the only product recommended for the first three doses. At present, acellular pertussis vaccines are approved only for the fourth and fifth doses for children 15 months or older.

The results of other pertussis vaccine trials in Italy and Sweden funded by the National Institute of Allergy and Infectious Diseases (NIAID) were announced last July. The NIAID-funded trials found that three acellular pertussis vaccines were highly effective against pertussis and had fewer side effects than the currently used whole-cell vaccine.

In addition to Dr. Robbins, other members of the research team were the study's first author, Birger Trollfors, MD; John Taranger, MD, Teresa Lagergard, PhD; Lena Lind, MD; Valter Sundh, BSc; and Gunilla Zackrisson, MD; all of Goteborg University in Goteborg, Sweden; Charles U. Lowe, MD, formerly of the NICHD; and William Blackwelder, PhD, of the NIAID.