Safety and immunogenicity of the epicutaneous reactivation of pertussis toxin immunity in healthy adults: a phase I, randomized, double-blind, placebo-controlled trial

Abstract

Objectives: Protection induced by acellular vaccines can be short, requiring novel immunization strategies. Objectives of this study were to evaluate safety and capacity of a recombinant pertussis toxin (PTgen) -coated Viaskin® epicutaneous patch to recall memory responses in healthy adults. Methods: This double-blind, placebo-controlled randomized trial (Phase I) assessed the safety and immunogenicity of PTgen administered on days 0 and 14 to healthy adults using Viaskin® patches applied directly or after epidermal laser-based skin preparation. Patch administration was followed by Boostrix®dTpa on day 42. Antibodies were assessed at days 0, 14, 28, 42 and 70.Results: Among 102 volunteers enrolled, 80 received Viaskin-PT (Viaskin-PT 25 mgIncidence of adverse events was similar across groups (any local event: 21/25 (84.0%), 24/25 (96.0%), 4/5 (80.0%), 24/25 (96.0%), 8/10 (80.0%), 10/12 (83.0%), respectively). Direct application induced no detectable response. On day 42, PT-IgG geometric mean concentrations were significantly higher following laser þ Viaskin-PT 25 mg and 50 mg (139.87 (95% CI 87.30e224.10) and 121.76 (95% CI 95.04e156.00), respectively), than laser þ Viaskin-placebo (59.49, 95% CI 39.37e89.90). Seroresponse rates were higher following laser þ Viaskin-PT 25 mg (4/5 (80.0%), 95% CI 28.4e99.5) and 50 mg (22/25 (88.0%), 95% CI 68.8e97.5) than laser þ Viaskin-placebo (0/12 (0.0%), 95% CI 0.0e26.5). Conclusions: Viaskin-PT applied after laser-based epidermal skin preparation showed encouraging safety and immunogenicity results: anti-PT booster responses were not inferior to those elicited by Boos-trix®dTpa. This study is registered at ClinicalTrials.gov (NCT 03035370) and was funded by DBV Technologies.

Phase I Study to Assess Safety of Laser-Assisted Topical Administration of an Anti-TNF Biologic in Patients With Chronic Plaque-Type Psoriasis

“…This leads to the conclusion that topical administration of ETA to psoriatic plaques via AFL-generated micropores in patients with plaque-type psoriasis is well-tolerated. The incidence of ASR was in line with other studies using the same Er:YAG laser system (12).…”

“…The strategy of enhancing drug delivery through skin micropores has recently been extensively used for various applications including vaccination (12), topical delivery of small molecules (13), proteins (9), and living human cells in vitro (14). Our pilot data provide a basis for further investigation of the combination of AFL + ETA in larger studies.…”

The Path to New Pediatric Vaccines against Pertussis

“…Pertussis vaccines are usually administered intramuscularly. As an alternative, epicutaneous delivery of a stand-alone aP vaccine, consisting only of genetically detoxified PT was tested and found to be safe, but the resulting immune responses were poor [ 61 ], although this approach showed promise in a mouse model [ 62 ]. Immunogenicity could, however, be improved when the skin was prepared by a laser beam prior to vaccine application [ 61 ].…”

Laser-facilitated epicutaneous immunization with SARS-CoV-2 spike protein induces ACE2 blocking antibodies in mice

“…We and others established generation of skin micropores via infrared laser beams as a painless and highly reproducible method to overcome the cornified outermost skin barrier and deliver large molecules such as biologicals [11–14]. This method has been recently tested in healthy human adults using epicutaneous patches containing recombinant pertussis toxin and was shown to induce recall antibody responses equivalent to those induced by injection of a commercial diphtheria-tetanus-acellular pertussis vaccine adjuvanted with alum [15].…”