InvestigatingBordetella pertussiscolonisation and immunity: protocol for an inpatient controlled human infection model

Abstract

IntroductionWe summarise an ethically approved protocol for the development of an experimental human challenge colonisation model. Globally Bordetella pertussis is one of the leading causes of vaccine-preventable death. Many countries have replaced whole cell vaccines with acellular vaccines over the last 20 years during which pertussis appears to be resurgent in a number of countries in the developed world that boast high immunisation coverage. The acellular vaccine provides relatively short-lived immunity and, in contrast to whole cell vaccines, may be less effective against colonisation and subsequent transmission. To improve vaccine strategies, a greater understanding of human B. pertussis colonisation is required. This article summarises a protocol and does not contain any results.Methods and analysisA controlled human colonisation model will be developed over two phases. In phase A, a low dose of the inoculum will be given intranasally to healthy participants. This dose will be escalated or de-escalated until colonisation is achieved in approximately 70% (95% CI 47% to 93%) of the exposed volunteers without causing disease. The colonisation period, shedding and exploratory immunology will be assessed during a 17-day inpatient stay and follow-up over 1 year. The dose of inoculum that achieves 70% colonisation will then be confirmed in phase B, comparing healthy participants exposed to B. pertussis with a control group receiving a sham inoculum.Ethics and disseminationThis study has been approved by the ethical committee reference: 17/SC/0006, 24 February 2017. Findings will be published in peer-reviewed open access journals as soon as possible.

Azithromycin Clears Bordetella pertussis Infection in Mice but Also Modulates Innate and Adaptive Immune Responses and T Cell Memory

“…The findings also suggested that sustained activation of innate and adaptive immune responses by PAMPs and antigen, respectively, for up to 14 days may be required for optimal induction of immunological memory. Finally, our findings have implications for antibiotic treatment of human volunteers exposed to B. pertussis in a human challenge model under development ( 33 ) and provide comfort that treatment with a single oral dose of macrolide antibiotics is an effective means of terminating the infection provided they are administered 1–2 weeks after the intranasal challenge with live B. pertussis .…”

Controlled human infection for vaccination against Streptococcus pyogenes (CHIVAS): Establishing a group A Streptococcus pharyngitis human infection study

“…However, no two challenges will be identical, depending on how the swab is rolled over the unique contours of each pharynx and how the procedure is tolerated. Alternative methods discussed included intranasal injection as in the non-human primate GAS nasopharyngitis model [47] and HIS for other respiratory pathogens [53][54][55][56]. The record of successful and safe induction of experimental pharyngitis in the 1970s was ultimately decisive in choosing the swab method.…”

Bordetella pertussis isolates vary in their interactions with human complement components

“…Tohama I and Wellcome 28 strains were included in these studies to compare how these strains differ in their interaction with complement components to more recently isolated UK strains and the Dutch isolate B1917 25 , which has been selected for use in a human challenge model 39 . Tohama I, a strain isolated in Japan in the 1950s and widely used in vaccine manufacture, and Wellcome 28 40 , a whole-cell vaccine strain, both do not express the type III secretion system effector Bsp22 41 .…”