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Pertussis vaccines effective against pertactin-deficient strains

Publish date: April 12, 2016
By
Mary Ann Moon

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Reassuring and expected findings

Immunity to pertussis from either natural infection or vaccination, is not lifelong. Two acellular pertussis vaccines are in widespread use in the United States, and they differ in the number and amounts of purified proteins and method of being chemically inactivated. A vaccine made by GlaxoSmithKline includes three proteins: pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin (PRN). A vaccine made by Sanofi Pasteur includes the same three proteins (PT, FHA, and PRN) plus two types of fimbriae (FIM), for a total of five ingredients. PT causes virtually all the symptoms of pertussis disease. The other proteins included in the two acellular vaccines are principally there to prevent the Bordetella pertussis bacteria from attaching to the nasopharynx and lung because prevention of attachment is a prevention of pathogenesis.

Although both acellular pertussis vaccines provide good protection, many reports support that acellular pertussis vaccines have shown waning immunity. One hypothesis among experts is that waning immunity might be related to changes in the protein structure of one or more of the targets for acellular vaccines. The protein that has been shown to have changed since introduction of acellular vaccines is PRN.

In the current study from Vermont, we learn that acellular pertussis vaccine efficacy remained high in that state despite the presence of over 90% of the B. pertussis strains lacking a PRN protein on the bacteria surface that would serve as an antibody target following vaccination. In other words, the lack of PRN as a vaccine target did not reduce vaccine efficacy nor did it impact the waning immunity following vaccination.

The result is reassuring and expected. All bacteria that seek to attach themselves to our respiratory tract in the nose or lungs or both have many different proteins to accomplish that attachment task. The redundancy of those proteins fits easily in a biologic necessity framework because pathogenesis cannot begin for any of the respiratory pathogenic bacteria unless they can attach themselves to the host in the nose or lungs or both. The addition of FHA as well as PRN in the GlaxoSmithKline vaccine and FHA plus two types of FIM antigen as ingredients in the Sanofi Pasteur vaccine was to raise antibody to multiple “adhesion” proteins. That way if “escape mutants” occurred, as we are now observing for PRN-deficient strains, the vaccines would still work. The study from Vermont tells us that they still do work.

Michael E. Pichichero, M.D., a specialist in pediatric infectious diseases, is director of the Research Institute, Rochester (N.Y.) General Hospital. He is also a pediatrician at Legacy Pediatrics in Rochester. Dr. Pichichero commented in an interview. He said he had no relevant financial disclosures.


 

FROM PEDIATRICS

References

Current pertussis vaccines were as effective against the rapidly evolving pertactin-deficient strains of the organism as they have been against other strains, according to a report published online April 13 in Pediatrics.

The proportion of pertussis strains lacking pertactin increased markedly in the United States, from 14% in 2010 to 85% in 2012. Pertactin, an autotransporter thought to be “involved in bacterial adhesion to the respiratory tract and resistance to neutrophil-induced bacterial clearance,” is a component of acellular pertussis vaccines. Some have speculated that pertactin deficiency evolved to give the bacteria an advantage in response to vaccine-related selection pressure, and that this evolution has contributed to the recent resurgence of pertussis disease, said Lucy Breakwell, Ph.D., of the epidemic intelligence service, Centers for Disease Control and Prevention, Atlanta, and her associates.

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To assess vaccine efficacy in the setting of pertactin deficiency, the investigators studied 820 cases and 2,369 matched control subjects treated in Vermont during a 3-year period encompassing a recent pertussis outbreak there. The study included children aged 4-10 years given the five-dose DTaP childhood series and adolescents aged 11-19 years given the adolescent Tdap dose. Specimens from these cases had been cultured routinely by the state department of health laboratory, and more than 90% of the available isolates were found to be pertactin deficient.

The overall vaccine efficacy of the DTap series was 84%, and of the Tdap booster, 70%. “Remarkably,” these rates are comparable to the 89% efficacy of DTap reported in a 2010 California outbreak and the 64% efficacy of Tdap reported in a 2012 Washington state outbreak, the investigators said. “Our findings suggest that both acellular pertussis vaccines remain protective against pertussis disease in the setting of high pertactin deficiency,” and therefore remain the best method for protecting against severe disease, Dr. Breakwell and her associates said (Pediatr. 2016 April 12. doi: 10.1542/peds.2015-3973).

Nevertheless, further study is warranted “to better understand the implications of pertactin deficiency on pertussis pathogenesis and host immunologic response, which could provide insight into the development of novel pertussis vaccines,” they wrote.

This study was supported by the Centers for Disease Control and Prevention. Dr. Breakwell and her associates reported having no relevant financial disclosures.

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