Induction of protective immunity against lethal anthrax challenge with a patch

J Infect Dis. 2004 Aug 15;190(4):774-82. doi: 10.1086/422694. Epub 2004 Jul 13.

Abstract

Background: Transcutaneous immunization (TCI) is a needle-free technique that delivers antigens and adjuvants to potent epidermal immune cells. To address critical unmet needs in biodefense against anthrax, we have designed a novel vaccine delivery system using a dry adhesive patch that simplifies administration and improves tolerability of a subunit anthrax vaccine.

Methods: Mice and rabbits were vaccinated with recombinant protective antigen of Bacillus anthracis and the heat-labile toxin of Escherichia coli. Serologic changes, levels of toxin-neutralizing antibodies (TNAs), and pulmonary and nodal responses were monitored in the mice. A lethal aerosolized B. anthracis challenge model was used in A/J mice, to demonstrate efficacy.

Results: The level of systemic immunity and protection induced by TCI was comparable to that induced by intramuscular vaccination, and peak immunity could be achieved with only 2 doses. The addition of adjuvant in the patch induced superior TNA levels, compared with injected vaccination.

Conclusions: Anthrax vaccine patches stimulated robust and functional immune responses that protected against lethal challenge. Demonstration of responses in the lung suggests that a mechanism exists for protection against challenge with aerosolized anthrax spores. A formulated, pressure-sensitive, dry adhesive patch, which is stable and can be manufactured in large scale, elicited comparable immunoglobulin G and TNA responses, suggesting that an anthrax vaccine patch is feasible and should advance into clinical evaluation.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic
  • Administration, Cutaneous
  • Animals
  • Anthrax / immunology
  • Anthrax / prevention & control*
  • Anthrax Vaccines / administration & dosage*
  • Anthrax Vaccines / immunology
  • Antibodies, Bacterial / analysis
  • Antibodies, Bacterial / biosynthesis
  • Antibodies, Bacterial / blood
  • Bacillus anthracis / immunology*
  • Bacterial Toxins / administration & dosage
  • Bacterial Toxins / immunology
  • Bronchoalveolar Lavage Fluid / immunology
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Enterotoxins / administration & dosage
  • Enterotoxins / immunology
  • Escherichia coli Proteins*
  • Lymph Nodes / immunology
  • Mice
  • Neutralization Tests
  • Rabbits
  • Recombinant Proteins / immunology
  • Time Factors
  • Vaccination*
  • Vaccines, Subunit / administration & dosage
  • Vaccines, Subunit / immunology

Substances

  • Adjuvants, Immunologic
  • Anthrax Vaccines
  • Antibodies, Bacterial
  • Bacterial Toxins
  • Enterotoxins
  • Escherichia coli Proteins
  • Recombinant Proteins
  • Vaccines, Subunit
  • heat-labile enterotoxin, E coli