Anthrax vaccination strategies

Abstract

The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune response but are hampered by shortcomings that make their widespread use undesirable or infeasible. Efforts to gain U.S. Food and Drug Administration (FDA) approval for licensure of a second generation recombinant protective antigen (rPA)-based anthrax vaccine are ongoing. However, this vaccine's reliance on the generation of a humoral immune response against a single virulence factor has led a number of scientists to conclude that the vaccine is likely not the final solution to optimal anthrax vaccine design. Other vaccine approaches, which seek a more comprehensive immune response targeted at multiple components of the B. anthracis organism, are under active investigation. This review seeks to summarize work that has been done to build on the current PA-based vaccine methodology and to evaluate the search for future anthrax prophylaxis strategies.

Surface architecture of endospores of the Bacillus cereus/anthracis/thuringiensis family at the subnanometer scale

“…In B. cereus and the closely related B. anthracis and B. thuringiensis, the exosporium is made up of a "basal" layer supporting a filamentous "hairy nap" (8) and is composed of proteins, lipid, and carbohydrate (9). Proteins of the exosporium are likely to have intimate interactions with the environment and are also potential candidates for vaccines and ligands for spore detection (10,11).…”

Intramuscular Delivery of Adenovirus Serotype 5 Vector Expressing Humanized Protective Antigen Induces Rapid Protection against Anthrax That May Bypass Intranasally Originated Preexisting Adenovirus Immunity

“…PA has been the principal target for the development of anthrax vaccines (6). Since PA is a prokaryotic antigen, codons of the PA gene sequence were optimized for human expression using the UpGene software.…”

“…Blood serum antigen-specific antibody and neutralizing antibody titers against anthrax PA after vaccination are the best correlates of protection against anthrax (6)(7)(8). The humoral immune responses of the Ad5-PAopt-immunized mice were measured using a direct enzyme-linked immunosorbent assay (ELISA) and toxin-neutralizing assay (TNA) (Fig.…”

“…Vaccination with an anthrax vaccine is the best strategy for preexposure and postexposure prophylaxis. Due to its central role in virulence, PA has been the principal target for the development of vaccines against anthrax (6)(7)(8). The first generation of such vaccines included Anthrax Vaccine Adsorbed (AVA) (BioThrax) in the United States and Anthrax Vaccine Precipitated (AVP) in the United Kingdom (6).…”

“…Due to its central role in virulence, PA has been the principal target for the development of vaccines against anthrax (6)(7)(8). The first generation of such vaccines included Anthrax Vaccine Adsorbed (AVA) (BioThrax) in the United States and Anthrax Vaccine Precipitated (AVP) in the United Kingdom (6). Although they provide good protection in various animal models and are readily tolerated in humans (9), multiple doses are required over a protracted period to achieve adequate levels of protective immunity, making these vaccines less than optimal for use in response to a bioterrorism incident.…”