Bordetella pertussis Polymorphism and Pertussis Vaccines

The topic of the article by Bottero et al. (1) is an important one, a bacterial vaccine for a preventable disease, pertussis. Many articles have been published on the subject in the last 10 years (for a review, see reference 6). In their study, Bottero et al. neither followed the recommendations of consensus meetings nor used published nomenclature. Furthermore, they compared vaccines that cannot be compared.

In the abstract and throughout the manuscript, the authors claim that the vaccines are not protecting against new circulating isolates. How can they say that during the clinical efficacy trials, the isolates circulating in the countries where these trials were performed differed from the vaccine strains (at least in Europe) and then say that the vaccines were still found to be efficacious? We all agree that the actual isolates “escape” the herd immunity, but with the high level of vaccination coverage and the efficacy of whole-cell vaccines, these isolates can be controlled in many countries.

According to the description in Materials and Methods (1), Bottero et al. also did not use standardized techniques. For the PCR diagnosis, they did not use the agreed-upon reference technique published in 2005 (7). For the pulsed-field gel electrophoresis (PFGE) analysis, they cite the reference paper of Mooi et al. (5) but did not follow all of its conditions, which are now used by all other teams in Europe and the United States (3). Further, they use numbers to differentiate the isolates which are similar to, but not the same as, those used by Mooi et al., and this is very confusing for all readers. Also, they write that the Tohama strain is a vaccine strain, which is not the case in their country. For the animal assay, they cite the reference paper authored by myself and my colleagues (4) but do not follow the same protocol. We did not use intraperitoneal administration and did not conclude that 1/10 of the human dose of the vaccine is the right dose for an animal. Furthermore, as this test is now one of the World Health Organization's assays for licensing vaccines (8), it is important to follow the procedures for this assay exactly. Also, how can anyone dare to compare an unidentified combined diphtheria-tetanus-whole-cell pertussis vaccine (no source, manufacturer, or other information provided) with a noncombined, apparently homemade vaccine with no description of the technique used to detoxify the bacteria?

In Results and Discussion of their paper (1), the authors omit any comparison or discussion of the data from Argentina that my colleagues and I obtained and published recently about the same isolates that they used (2). Nor do they refer to the many studies performed in Europe and elsewhere on the same topic. The data presented concerning the animal model include the data at day 5 but no data for day 8. They neither discuss nor cite data previously published on whole-cell pertussis vaccine-induced immunity against infection due to different isolates, but they do present a superficial analysis of one clinical isolate without any confirmation of the data for at least two or three other isolates of the same PFGE groups.

For these many and various reasons, I advise caution in interpreting the paper of Bottero et al., which sits uncomfortably with much of the already available literature on pertussis strains.