Acellular Pertussis Vaccine May Not Prevent Transmission

Laurie Barclay, MD

December 02, 2013

Acellular pertussis vaccines protected against disease but did not prevent infection and transmission, whereas whole-cell vaccines were more effective, according to findings from a primate model study published November 25 in the Proceedings of the National Academy of Sciences.

"There were 48,000 [pertussis] cases reported [in the United States] last year despite high rates of vaccination," Anthony S. Fauci, MD, director of the National Institute of Health's National Institute of Allergy and Infectious Diseases, said in a news release. "This resurgence suggests a need for research into the causes behind the increase in infections and improved ways to prevent the disease from spreading."

Factors underlying increased incidence of whooping cough may include diminished immunity from childhood pertussis vaccines, improved diagnostic testing, and increased reporting.

Findings of the present study may help explain rising US rates of whooping cough and response to vaccination following replacement of whole-cell vaccines by acellular vaccines in the 1990s. The former contain killed, but complete, Bordetella pertussis bacteria, whereas the latter uses only selected portions of pertussis bacteria to stimulate the immune response. Despite concerns about adverse effects of whole-cell pertussis vaccines, they are still used in many other countries.

"Pertussis rates in the United States have been rising," write Jason M. Warfel, from the Division of Bacterial, Parasitic and Allergenic Products, Center for Biologics Evaluation and Research, US Food and Drug Administration (FDA), in Bethesda, Maryland, and colleagues. "Although pertussis resurgence is not completely understood, we hypothesize that current acellular pertussis vaccines fail to prevent colonization and transmission."

To test this hypothesis, the investigators vaccinated infant baboons at 2, 4, and 6 months of age with acellular pertussis or whole-cell pertussis vaccines and challenged them with B pertussis at 7 months. For infected animals, the investigators quantified colonization in nasopharyngeal washes and monitored leukocytosis and symptoms.

Acellular Vaccine Did Not Prevent Transmission

An unvaccinated control group contracted pertussis. Neither vaccinated group showed symptoms of pertussis, and both vaccinated groups had robust antibody responses.

Baboons immunized with whole-cell vaccine were bacteria-free within 3 weeks, but bacterial nasal colonization was present for up to 6 weeks in baboons that received the acellular vaccine, as well as in those that were not vaccinated. Of even greater concern was that the pertussis bacteria were transmitted from baboons that received acellular vaccine to unvaccinated baboons.

"This study is critically important to understanding some of the reasons for the rising rates of pertussis and informing potential strategies to address this public health concern," Karen Midthun, MD, director of the FDA's Center for Biologics Evaluation and Research, said in a news release. "This research is a valuable contribution and brings us one step closer to understanding the problem. We are optimistic that more research on pertussis will lead to the identification of new and improved methods for preventing the disease."

Limitations of this study include those inherent in the baboon model and in the assay used to measure immunity.

"While all groups possessed robust antibody responses, key differences in T-cell memory suggest that [acellular pertussis] vaccination induces a suboptimal immune response that is unable to prevent infection," the study authors write. "These data provide a plausible explanation for pertussis resurgence and suggest that attaining herd immunity will require the development of improved vaccination strategies that prevent B. pertussis colonization and transmission."

The FDA and the National Institutes of Health/National Institute of Allergy and Infectious Diseases supported this study. The study authors have disclosed no relevant financial relationships.

Proc Natl Acad Sci. Published online November 25, 2013. Abstract

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