Article

N-fragment of edema factor as a candidate antigen for immunization against anthrax.

Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 672, Rochester, NY 14642, USA.
Vaccine (impact factor: 3.77). 02/2006; 24(5):662-70. DOI:10.1016/j.vaccine.2005.08.056 pp.662-70
Source: PubMed

ABSTRACT The nontoxic N-terminal fragment of Bacillus anthracis edema factor (EF) was evaluated as a candidate antigen in an anthrax vaccine using a replication-incompetent adenoviral vector. An E1/E3 deleted adenovirus (Ad/EFn) encoding the N-terminal region 1-254 amino acids of the edema factor (EFn) was constructed using the native DNA sequence of EFn. Intramuscular immunization three times with 10(8) plaque forming units (pfu)/dose of Ad/EFn in A/J mice resulted in 37% and 57% protection against a subcutaneous challenge with B. anthracis Sterne strain spores at a dosage of 200 x LD50 and 100 x LD50, respectively. EF-specific serum IgG responses (including total IgG, IgG1, and IgG2a isotype titers) were robust in the Ad/EFn immunized animals. Interestingly, anti-EF antibodies cross-reacted with anthrax lethal factor (LF), and had a neutralizing capability against both anthrax lethal toxin (Letx) and edema toxin (Edtx), as demonstrated by in vitro toxin neutralization assays using J774A.1 mouse macrophage and Chinese hamster ovary cell (CHO), respectively. Our data suggest that EF plays a role in eliciting protective immunity against anthrax, and that it should be included in a new generation multi-component subunit vaccine.

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    Article: Effect of aluminum hydroxide adjuvant and formaldehyde in the formulation of rPA anthrax vaccine.
    S F Little, B E Ivins, W M Webster, S L W Norris, G P Andrews
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    ABSTRACT: The serological response and efficacy of Bacillus anthracis recombinant protective antigen (rPA) vaccines formulated with aluminum hydroxide adjuvant, either with or without formaldehyde, were evaluated in rabbits. Rabbits that had been injected with a single dose of 25 microg of rPA adsorbed to 500 microg of aluminum in aluminum hydroxide gel (Alhydrogel) had a significantly higher quantitative anti-rPA IgG ELISA titers (p<0.0001) and toxin neutralizing antibody (TNA) assay titers (p<0.0001) than rabbits tested at the next lowest concentration of aluminum (158 microg). Rabbits injected with two doses of 50 microg of rPA formulated with 500 microg of aluminum also had significantly higher serological responses, as measured by a quantitative anti-rPA IgG ELISA (p<0.0001) and TNA assay (p<0.0001), than sera from rabbits injected with a rPA vaccine formulated without adjuvant. Short-term protection against an aerosol spore challenge (448 LD(50)), however, was not significantly different between the two groups (12/12 and 11/12, respectively). Rabbits injected with a single dose of 50 microg of rPA formulated with 500 microg of aluminum and 0.2% formaldehyde had significantly higher ELISA (p<0.0001) and TNA assay (p<0.0001) titers than rabbits that had been injected with a rPA vaccine formulated with adjuvant but without formaldehyde. Short-term protection against a 125 LD(50) parenteral spore challenge, however, was not significantly different between the two groups (14/24 and 9/24, respectively; p=0.2476). Under the conditions tested in the rabbit animal model, significantly higher serological responses were observed in rabbits that had been injected with rPA formulated with aluminum hydroxide gel adjuvant and formaldehyde. However, differences in short-term efficacy were not observed.
    Vaccine 05/2007; 25(15):2771-7. · 3.77 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

Ad/EFn immunized animals
 
anthrax
 
anthrax lethal factor
 
anthrax lethal toxin
 
anthrax vaccine
 
anti-EF antibodies cross-reacted
 
B. anthracis Sterne strain spores
 
Bacillus anthracis edema factor
 
candidate antigen
 
Chinese hamster ovary cell
 
edema toxin
 
N-terminal region 1-254 amino acids
 
native DNA sequence
 
neutralizing capability
 
new generation multi-component subunit vaccine
 
nontoxic N-terminal fragment
 
replication-incompetent adenoviral vector
 
subcutaneous challenge
 
total IgG
 
vitro toxin neutralization assays