The introduction of pertussis vaccines greatly decreased the incidence of pertussis disease and mortality [1]. buy Bioactive Compound Library There are two types of available pertussis vaccines, whole-cell (Pw) and acellular (Pa). The first dose of the vaccine is given at the age of 2–3 months [2], [3] and [4]. Infants

below four months are thus not optimally protected and are at risk for severe and fatal pertussis [5]. Improving the current immunization scheme so that young infants are offered protection is therefore important. A natural pertussis infection induces a type I T-helper (Th1) cell response, and clearing of the primary infection depends on interferon gamma (IFN-γ) production [6] and [7]. Mouse studies have shown a protective role for B cells as well MK1775 [8] and [9]. In children, Pw-vaccines are reported to induce a Th1-type profile like a natural infection, whereas Pa-vaccinated children are seen to induce a more Th1/Th2-mixed type of response [10] and [11]. Mielcarek et al. have developed a live attenuated B. pertussis vaccine strain named BPZE1 [12] with the long-term aim to administer it to infants at birth. This vaccine strain is attenuated by genetic removal of the dermonecrotic toxin and the tracheal cytotoxin as well as detoxification of the pertussis toxin (PT). These alterations have not affected the immunogenic properties [12], and the strain has been

shown to be genetically stable after both continuous in vitro and in vivo passages over at least one year [13]. It can colonize the respiratory tract and induce long-lasting memory B-cell responses, as well as T-cell mediated protective immunity against challenge in mice [12], [14] and [15]. A recent randomized, placebo-controlled, double-blind, dose-escalating phase I clinical trial has shown that BPZE1 is safe in humans, able to transiently colonize the human nasopharynx

and to induce antibody responses [16]. Here, we have evaluated B-cell responses after vaccination with BPZE1. Plasma blast- and memory B-cell responses were detected by ELISpot, and B-cell subsets were second identified by flow cytometry. The study was conducted according to the protocol ICH Good Clinical Practices standards, Declaration of Helsinki and applicable regulatory requirements as well as any related European and Swedish applicable laws and regulations. The trial was registered at ClinicalTrials.gov (NCT01188512) and approved by the Swedish Medical Product Agency and the regional ethical review board in Stockholm. All volunteers signed an informed consent form after receiving oral and written information in Swedish. The clinical BPZE1 lots were produced by Innogenetics (Ghent, Belgium) as a suspension in phosphate-buffered saline (PBS) containing 5% saccharose. Three doses of BPZE1 were tested, 103 colony forming units (cfu), 105 cfu and 107 cfu, as described earlier [16].