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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.
Paolino, Kristopher M; Regules, Jason A; Moon, James E; Ruck, Richard C; Bennett, Jason W; Remich, Shon A; Mills, Kristin T; Lin, Leyi; Washington, Cadeidre N; Fornillos, Ghariwayne A; Lindsey, Changhong Y; O'Brien, Kristan A; Shi, Meng; Mark Jones, R; Green, Brian J; Tottey, Stephen; Chichester, Jessica A; Streatfield, Stephen J; Yusibov, Vidadi.
Afiliación
  • Paolino KM; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Regules JA; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA; United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Moon JE; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Ruck RC; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Bennett JW; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Remich SA; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Mills KT; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Lin L; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Washington CN; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Fornillos GA; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Lindsey CY; United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • O'Brien KA; United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
  • Shi M; Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
  • Mark Jones R; Fraunhofer USA Center Mid-Atlantic, Biotechnology Division, Newark, DE 19711, USA.
  • Green BJ; Fraunhofer USA Center Mid-Atlantic, Biotechnology Division, Newark, DE 19711, USA.
  • Tottey S; Fraunhofer USA Center Mid-Atlantic, Biotechnology Division, Newark, DE 19711, USA.
  • Chichester JA; Fraunhofer USA Center Mid-Atlantic, Biotechnology Division, Newark, DE 19711, USA.
  • Streatfield SJ; Fraunhofer USA Center Mid-Atlantic, Biotechnology Division, Newark, DE 19711, USA. Electronic address: sstreatfield@fraunhofer.org.
  • Yusibov V; Fraunhofer USA Center Mid-Atlantic, Biotechnology Division, Newark, DE 19711, USA.
Vaccine ; 40(12): 1864-1871, 2022 03 15.
Article en En | MEDLINE | ID: mdl-35153091
ABSTRACT

BACKGROUND:

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.

METHODS:

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.

RESULTS:

All four-dose ranges were safe and immunogenic, with no related serious adverse events observed. Peak ELISA Geometric Mean Concentration (GMC) and TNA ED50 Geometric Mean Titer (GMT) were noted at Day 84, 1 month after the final dose, with the most robust response detected in the highest dose group. Antibody responses decreased by Day 180 across all dose groups. Long-term immunogenicity data beyond six months was not collected.

CONCLUSIONS:

This 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.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bacillus anthracis / Vacunas contra el Carbunco / Carbunco Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Humans Idioma: En Revista: Vaccine Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bacillus anthracis / Vacunas contra el Carbunco / Carbunco Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Humans Idioma: En Revista: Vaccine Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos