Mucosal Immunization Against Pertussis: Lessons From the Past and Perspectives

Abstract

BackgroundCurrent vaccination strategies against pertussis are sub-optimal. Optimal protection against Bordetella pertussis, the causative agent of pertussis, likely requires mucosal immunity. Current pertussis vaccines consist of inactivated whole B. pertussis cells or purified antigens thereof, combined with diphtheria and tetanus toxoids. Although they are highly protective against severe pertussis disease, they fail to elicit mucosal immunity. Compared to natural infection, immune responses following immunization are short-lived and fail to prevent bacterial colonization of the upper respiratory tract. To overcome these shortcomings, efforts have been made for decades, and continue to be made, toward the development of mucosal vaccines against pertussis.ObjectivesIn this review we systematically analyzed published literature on protection conferred by mucosal immunization against pertussis. Immune responses mounted by these vaccines are summarized.MethodThe PubMed Library database was searched for published studies on mucosal pertussis vaccines. Eligibility criteria included mucosal administration and the evaluation of at least one outcome related to efficacy, immunogenicity and safety.ResultsWhile over 349 publications were identified by the search, only 63 studies met the eligibility criteria. All eligible studies are included here. Initial attempts of mucosal whole-cell vaccine administration in humans provided promising results, but were not followed up. More recently, diverse vaccination strategies have been tested, including non-replicating and replicating vaccine candidates given by three different mucosal routes: orally, nasally or rectally. Several adjuvants and particulate formulations were tested to enhance the efficacy of non-replicating vaccines administered mucosally. Most novel vaccine candidates were only tested in animal models, mainly mice. Only one novel mucosal vaccine candidate was tested in baboons and in human trials.ConclusionThree vaccination strategies drew our attention, as they provided protective and durable immunity in the respiratory tract, including the upper respiratory tract: acellular vaccines adjuvanted with lipopeptide LP1569 and c-di-GMP, outer membrane vesicles and the live attenuated BPZE1 vaccine. Among all experimental vaccines, BPZE1 is the only one that has advanced into clinical development.

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

“…Above all, given that pertussis is acquired through the respiratory tract, nasally administered vaccines that stimulate mucosal immunity may prove more efficacious than vaccines eliciting solely systemic responses [274,275]. A variety of intranasal pertussis vaccines have been investigated in recent years along with different adjuvants; the most promising options include OMV or the live-attenuated BPZE1 vaccines, shown to effectively induce antigen-specific mucosal CMI and confer protection against both nasal and lung colonisation (Table 1).…”

Bps polysaccharide of Bordetella pertussis resists antimicrobial peptides by functioning as a dual surface shield and decoy and converts Escherichia coli into a respiratory pathogen

“…Pertussis is traditionally described as a childhood disease, which results in severe and sometimes fatal infections in newborns and infants. There has also been an increase in infections of vaccinated adolescents and adults, in whom pertussis manifests as a persistent cough with milder symptoms [1][2][3][4].…”

Blockade of the Adenylate Cyclase Toxin Synergizes with Opsonizing Antibodies to Protect Mice against Bordetella pertussis

“… B. pertussis colonizes the upper and lower respiratory tracts, and there is a growing consensus that immune responses in these tissues will be crucial to protect against disease and reduce transmission ( 63 ). Notably, protection by anti-ACT antibodies in this work was observed after direct administration to the respiratory tract intranasal but not systemic administration ( Fig.…”