Immune response to two different dosing schedules of the anthrax vaccine precipitated (AVP) vaccine

Hepburn, Matthew J.; Dyson, E.H.; Simpson, Andrew J. H.; Brenneman, Karen E.; Bailey, N. E.; Wilkinson, Lucy J.; Hornby, Rebecca J.; Mateczun, Alfred; Bell, Matthew; Baillie, Les

doi:10.1016/j.vaccine.2007.05.018

Cited by 24 publications

(24 citation statements)

References 22 publications

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“…Because LT contains two toxin components, we used this principle to show that changes in rPA, but not rLF, concentration followed this inverse correlation with ED 50 of all test sera (except that of anti-rLF sera, which showed an expected inverse correlation with rLF concentration). The rPA component was the determining factor of neutralizing potencies of all test sera because those samples contained either anti-PA antibodies only (i.e., from rPA plus Alhydrogel vaccination) or substantially greater anti-PA neutralizing content relative to that of anti-LF that is expected in sera derived from AVA vaccinations with or without CPG 7909 (11,12). Indeed, most anthrax vaccines in development are designed to induce a strong neutralizing anti-PA antibody titer as the predominant protective mechanism (11)(12)(13)(14), in which case the rPA concentration, rather than the rLF concentration, would be the dominant component in those respective TNAs.…”

Section: Discussionmentioning

confidence: 99%

“…8B to D). This additive contribution of each antibody fraction was not significant when the ratio of anti-rPA to anti-rLF serum activity was increased to the natural ratios of Ͼ10:1 ob- served after AVA immunization (11,12) (Fig. 8E and F).…”

Section: Biochemical Characterization Of Rlf Lotsmentioning

confidence: 90%

“…We hypothesized that the reason for the rPA component of LT in the TNA being the determining factor of serum potency (ED 50 ) is that the anti-PA antibody content in sera derived from AVA immunization was represented in substantially greater levels than anti-LF (i.e., the natural anti-PA/anti-LF ratio of Ͼ10:1 [11,12,14]), causing a dominance of rPA activity in the TNA. Accordingly, there would be rLF dominance in the TNA if the anti-LF antibody fraction was in excess or a codominance of rPA and rLF activities if similar levels of both antibody fractions were present.…”

Section: Biochemical Characterization Of Rlf Lotsmentioning

confidence: 99%

“…Serum titers of anthrax LT-neutralizing antibodies following vaccination have been evaluated in animal models of anthrax disease and in human clinical immunogenicity studies (7)(8)(9)(10). While antibodies to all toxin components can be detected via an enzymelinked immunosorbent assay (ELISA) after vaccination with AVA, serum titers of antibodies to PA are most prevalent and appear to be responsible mainly for LT-neutralizing activity in the anthrax toxin neutralization assay (TNA) (11)(12)(13)(14). In fact, most reported TNAs were designed to emphasize this anti-PA antibody neutralizing contribution, which is the best-accepted correlate of immune protection for certain anthrax vaccine formulations (15)(16)(17).…”

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confidence: 99%

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Characterization of the Native Form of Anthrax Lethal Factor for Use in the Toxin Neutralization Assay

Catania

Baranji

et al. 2013

Clin. Vaccine Immunol.

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The cell-based anthrax toxin neutralization assay (TNA) is used to determine functional antibody titers of sera from animals and humans immunized with anthrax vaccines. The anthrax lethal toxin is a critical reagent of the TNA composed of protective antigen (PA) and lethal factor (LF), which are neutralization targets of serum antibodies. Cytotoxic potency of recombinant LF (rLF) lots can vary substantially, causing a challenge in producing a renewable supply of this reagent for validated TNAs. To address this issue, we characterized a more potent rLF variant (rLF-A) with the exact native LF amino acid sequence that lacks the additional N-terminal histidine and methionine residues present on the commonly used form of rLF (rLF-HMA) as a consequence of the expression vector. rLF-A can be used at 4 to 6 ng/ml (in contrast to 40 ng/ml rLF-HMA) with 50 ng/ml recombinant PA (rPA) to achieve 95 to 99% cytotoxicity. In the presence of 50 ng/ml rPA, both rLF-A and rLF-HMA allowed for similar potencies (50% effective dilution) among immune sera in the TNA. rPA, but not rLF, was the dominant factor in determining potency of serum samples containing anti-PA antibodies only or an excess of anti-PA relative to anti-rLF antibodies. Such anti-PA content is reflected in immune sera derived from most anthrax vaccines in development. These results support that 7-to 10-fold less rLF-A can be used in place of rLF-HMA without changing TNA serum dilution curve parameters, thus extending the use of a single rLF lot and a consistent, renewable supply.

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Section: Discussionmentioning

confidence: 99%

Section: Biochemical Characterization Of Rlf Lotsmentioning

confidence: 90%

Section: Biochemical Characterization Of Rlf Lotsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Characterization of the Native Form of Anthrax Lethal Factor for Use in the Toxin Neutralization Assay

Catania

Baranji

et al. 2013

Clin. Vaccine Immunol.

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“…Unlike the AVA vaccine, AVP contains all three toxin components, with roughly 7.9 g/ml PA, 1.9 g/ml LF, and detectable amounts of EF (26). Vaccination with AVP consists of 4 intramuscular doses, administered at 0, 3, 6, and 32 weeks, with annual boosters (28).…”

mentioning

confidence: 99%

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

Dumas

Gross

Larabee

et al. 2017

Clin Vaccine Immunol

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Edema toxin (ET), composed of edema factor (EF) and protective antigen (PA), is a virulence factor of Bacillus anthracis that alters host immune cell function and contributes to anthrax disease. Anthrax vaccine precipitated (AVP) contains low but detectable levels of EF and can elicit EF-specific antibodies in human recipients of AVP. Active and passive vaccination of mice with EF can contribute to protection from challenge with Bacillus anthracis spores or ET. This study compared humoral responses to ET in recipients of AVP (n ϭ 33) versus anthrax vaccine adsorbed (AVA; n ϭ 66), matched for number of vaccinations and time postvaccination, and further determined whether EF antibodies elicited by AVP contribute to ET neutralization. AVP induced higher incidence (77.8%) and titer (229.8 Ϯ 58.6) of EF antibodies than AVA (4.2% and 7.8 Ϯ 8.3, respectively), reflecting the reported low but detectable presence of EF in AVP. In contrast, PA IgG levels and ET neutralization measured using a luciferase-based cyclic AMP reporter assay were robust and did not differ between the two vaccine groups. Multiple regression analysis failed to detect an independent contribution of EF antibodies to ET neutralization in AVP recipients; however, EF antibodies purified from AVP sera neutralized ET. Serum samples from at least half of EF IgG-positive AVP recipients bound to nine decapeptides located in EF domains II and III. Although PA antibodies are primarily responsible for ET neutralization in recipients of AVP, increased amounts of an EF component should be investigated for the capacity to enhance next-generation, PA-based vaccines.

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Vaccines for preventing anthrax

Donegan

Bellamy

2009

Cochrane Database of Systematic Reviews

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Immune response to two different dosing schedules of the anthrax vaccine precipitated (AVP) vaccine

Cited by 24 publications

References 22 publications

Characterization of the Native Form of Anthrax Lethal Factor for Use in the Toxin Neutralization Assay

Characterization of the Native Form of Anthrax Lethal Factor for Use in the Toxin Neutralization Assay

Anthrax Vaccine Precipitated Induces Edema Toxin-Neutralizing, Edema Factor-Specific Antibodies in Human Recipients

Vaccines for preventing anthrax

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