JAMA Study Finds Whooping Cough Vaccine Effective, Safe for Teens and Adults
New Class of Vaccine Arrives as Incidence Climbs Rapidly
Thursday, June 2, 2005
The arrival of a new combination vaccine for diphtheria, tetanus and pertussis represents a major advance.
The Journal of the American Medical Association announced today that a study to be published in the June 22/29 issue found that a new vaccine against whooping cough is effective in teens and adults, carriers of the contagious respiratory disease so dangerous to unvaccinated infants. Until recently, teens and adults have been unable to be vaccinated with available pediatric whooping cough vaccines due to safety concerns.
Whooping cough, caused by B. pertussis bacteria, triggers violent coughing spells that may last for months in infants as mucous clogs their smaller air passages. A coughing spell may last so long that the child gasps for breath, making a whooping sound. In 1934, more than 265,000 cases were reported in the United States with nearly 8,000 deaths, mostly in children. In 2003, the number of deaths was 13.
Vaccination programs in children have reduced the threat, but the infection rate is now climbing rapidly among teens and adults. While the whooping cough, or pertussis, is less severe with age and often mistaken for bronchitis, teens and adults serve as reservoirs for infection in infants who are too young to be immunized. In addition, the complications of pertussis in some adults can include pneumonia, rib fractures and seizures. In 2004, nearly 19,000 new cases of mostly adult cases of pertussis were reported to the Centers for Disease Control and Prevention (CDC), up from 12,000 in 2003. Due to large-scale misdiagnosis, some experts believe that between one and two million U.S. adults and adolescents may now become infected annually.
“The arrival of a new combination vaccine for diphtheria, tetanus and pertussis represents a major advance,” said Michael Pichichero, M.D., lead investigator of the JAMA study and professor of Microbiology, Immunology, Pediatrics, and Medicine at the University of Rochester Medical Center. “Widespread use of the new acellular vaccines has the potential to counter a quadrupling of the pertussis infection rate in teens and adults in the last three years.”
The approved, pediatric versions of the pertussis vaccine administered to American infants provides protection that begins to fade in the teenage years. For tetanus and diphtheria, adults receive booster shots to “remind” the immune system to be on watch for a given disease. The original children’s pertussis vaccine, however, caused severe injection site reactions in adults. Even newer versions of the pediatric vaccine caused excessive swelling in adults, precluding their use in booster shots until now. In the latest round of innovation, vaccine designers reduced the amount of bacterial ingredient in the vaccine and found that effective immune protection could be achieved with fewer side effects.
Traditionally, vaccines were made of either dead, or alive but weakened, versions of the “whole body” of the organism causing a disease (e.g. a virus or bacterium). Ideally, the immune system would recognize the vaccine agent as foreign, then destroy and “remember” it. When harmful versions of the pathogen later arrived, the immune system would be prepared.
Reacting to a Japanese outbreak in the 1980s, pharmaceutical companies there (e.g. Takeda) designed pertussis vaccines that were based not on entire cell bodies, but instead on a few key proteins on the surface of the bacteria (acellular or component vaccines) by which the human immune system recognized them as foreign intruders. Researchers realized that these acellular vaccines created comparable immunity with whole cell vaccines, but with the potential for less severe swelling reactions at the site of the injection. Virtually all second-generation vaccines are now acellular.
Over the last 20 years, Pichichero has been one of few voices arguing nationally that acellular vaccines were needed in the United States after seeing severe reactions to whole cell body pertussis vaccine in his own children. During decades of debate, many leading researchers felt that whole cell vaccines were adequate, and that reports of severe reactions to first generation, whole cell vaccines were exaggerated.
“After the experience I had with my children, I knew the problem was real,” Pichichero said. “Since then, our team at the University of Rochester has been a leading advocate for the use of acellular pertussis vaccines in infants and toddlers. Now with the availability of acelluar pertussis vaccines for adolescents and adults, we can complete the cycle of immunization with booster shots to finally eliminate whooping cough in the United States.”
The JAMA study 5-component vaccine is composed of four protein fragments from the pertussis bacterium that help it cling to lung tissue, as well as one toxin given off by the bacteria. Researchers found that the study vaccine provided effective immune protection with few adverse reactions, typically on par with the limited swelling and pain experienced during a tetanus shot, Pichichero said.
JAMA study participants were between the ages of 11 and 64 years. Researchers compared an experimental combination vaccine against pertussis, tetanus and diphtheria (Tdap, trade name Adacel™, sanofi pasteur) to a currently licensed tetanus-diphtheria (Td) booster for adolescents and adults and to the current childhood diphtheria-tetanus-acellular pertussis vaccine (DTaP). Researchers found that this Tdap vaccine provided comparable levels of immunity to that of the Td booster, and to the pertussis component of DTaP (licensed pediatric) vaccine. The level of adverse events was also similar between participants who received Tdap and Td vaccines.
The study examined the immunogenicity (immune response) and safety of Tdap experimental vaccine in a randomized, double-blind, comparative trial of 4,480 participants between the ages of 11 and 64 at 39 clinical centers across the U.S. Participants received a single 0.5mL intramuscular dose of either Tdap or Td vaccine; antibody titers (concentrations) were measured before injection and at 28 days. Pertussis antibody titers were compared to infants who received an equivalent pediatric diphtheria, tetanus and acellular pertussis vaccine (DTaP) in a previous efficacy trial. Participants were monitored for reactions to Tdap vaccine for 14 days and for adverse events for six months following vaccination.
Results of the study indicated that the Tdap vaccine elicited robust immune responses in adolescents and adults to pertussis, tetanus and diphtheria antigens. Specific findings include:
- For both Tdap and Td, greater than 94 percent and nearly 100 percent of participants had protective antibody concentrations (≥0.1 IU/mL) against diphtheria and tetanus, respectively.
- Geometric mean titers for four key pertussis antigens exceeded levels seen in infants (by 2.1 to 5.4 times) following immunization with DTaP at 2, 4 and 6 months.
- Booster response rates to the each of the four pertussis antigens ranged from 86 percent to 95 percent in adolescents, and 83 percent to 94 percent in adults.
The Tdap vaccine also exhibited an overall safety profile similar to that of the currently licensed Td vaccine. The most common adverse events in both adolescents and adults in the study included pain, redness of the skin and swelling at the site of injection.
The experimental vaccine is under review by the U.S. Food and Drug Administration. If approved, it would become the second of two pertussis booster vaccines to become available this year. The first, Boostrix, made by GlaxoSmithKline, was approved on May 17, but only for patients aged 10 to 18. On June 29, the Advisory Committee on Immunization Practices of the Centers for Disease Control is scheduled to meet on the issue of whether or not to recommend that one or both of the new vaccines be combined with routine booster shots for tetanus and diphtheria as part of mass immunization programs.