Safety and immunogenicity of a plant-derived recombinant protective antigen (rPA)-based vaccine against Bacillus anthracis: A Phase 1 dose-escalation study in healthy adults
| Autor: | Kristopher M, Paolino, Jason A, Regules, James E, Moon, Richard C, Ruck, Jason W, Bennett, Shon A, Remich, Kristin T, Mills, Leyi, Lin, Cadeidre N, Washington, Ghariwayne A, Fornillos, Changhong Y, Lindsey, Kristan A, O'Brien, Meng, Shi, R, Mark Jones, Brian J, Green, Stephen, Tottey, Jessica A, Chichester, Stephen J, Streatfield, Vidadi, Yusibov |
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| Rok vydání: | 2022 |
| Předmět: |
Adult
Antigens Bacterial General Veterinary General Immunology and Microbiology Public Health Environmental and Occupational Health Anthrax Vaccines Antigens Plant Antibodies Bacterial Anthrax Immunogenicity Vaccine Infectious Diseases Bacillus anthracis Humans Molecular Medicine Single-Blind Method |
| Zdroj: | Vaccine. 40:1864-1871 |
| ISSN: | 0264-410X |
| Popis: | The potential use of Bacillus anthracis as a bioterrorism weapon requires a safe and effective vaccine that can be immediately distributed for mass vaccination. Protective antigen (PA), a principal component of virulence factors edema toxin and lethal toxin of B. anthracis, has been the topic of extensive research. Previously, full-length PA (PA83) was manufactured using a transient plant-based expression system. Immunization with this PA83 antigen formulated with Alhydrogel® adjuvant elicited strong neutralizing immune responses in mice and rabbits and protected 100% of rabbits from a lethal aerosolized B. anthracis challenge. This Phase 1 study evaluates this vaccine's safety and immunogenicity in healthy human volunteers.This first-in-human, single-blind, Phase 1 study was performed at a single center to investigate the safety, reactogenicity, and immunogenicity of the plant-derived PA83-FhCMB vaccine at four escalating dose levels (12.5, 25, 50 or 100 µg) with Alhydrogel® in healthy adults 18-49 years of age (inclusive). Recipients received three doses of vaccine intramuscularly at 28-day intervals. Safety was evaluated on days 3, 7, and 14 following vaccination. Immunogenicity was assessed using an enzyme-linked immunosorbent assay (ELISA) and a toxin neutralizing antibody (TNA) assay on days 0, 14, 28, 56, 84, and 180.All four-dose ranges were safe and immunogenic, with no related serious adverse events observed. Peak ELISA Geometric Mean Concentration (GMC) and TNA EDThis is the first study demonstrating a plant-derived subunit anthrax vaccine's safety and immunogenicity in healthy adults. The results support further clinical investigation of the PA83-FhCMB vaccine. ClinicalTrials.gov identifier. NCT02239172. |
| Databáze: | OpenAIRE |
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