Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series☆

Pittman, Phillip R.; Norris, Sarah L.; Oro, Julio G. Barrera; Bedwell, David M.; Cannon, Timothy Lewis; McKee, Kelly T.

doi:10.1016/j.vaccine.2006.01.054

Cited by 43 publications

(33 citation statements)

References 25 publications

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“…Serological noninferiority analyses for peak anti-PA IgG and lethal toxin neutralization activity (TNA) in response to the 3-IM priming schedule and alternative booster schedules were reported previously, and the safety profile of AVA administered IM in humans was confirmed to be similar to that for other alum-containing vaccines (4)(5)(6). Less frequent AVA injection doses resulted in a reduction in some injection site adverse events (AEs), and IM administration resulted in reduced frequency, duration, and severity of AEs (5)(6)(7)(8)(9)(10)(11). The potential for increasing the intervals between booster doses requires an assessment of sustained antibody functional activity, CMI, and the ability to develop rapid protective anamnestic responses (5,6,12).…”

mentioning

confidence: 63%

Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

Quinn

Sabourin

Schiffer

et al. 2016

Clin Vaccine Immunol

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A nthrax vaccine adsorbed (AVA; BioThrax; Emergent Bio Solutions Inc., Lansing, MI) is the only Food and Drug Administration (FDA)-approved vaccine in the United States for prevention of anthrax in humans. The primary immunogen in AVA is anthrax toxin protective antigen (PA). Serum anti-PA antibody levels are accurate immune correlates of protection in nonhuman primate (NHP) models of inhalation anthrax and for predicted probability of survival in humans (1-3). There is a significant lack of data in humans regarding the onset, duration, quantitative analysis, and functional activity of humoral antibody and cell-mediated immunity (CMI) responses following priming and boosting with AVA.In 2012, the preexposure schedule for AVA was approved as a priming series of three 0.5-ml intramuscular (IM) injections at 0, 1, and 6 months (3-IM) with subsequent boosters at 12 and 18 months and annually thereafter for those at continued risk of infection (http://www.fda.gov/BiologicsBloodVaccines/Vaccines /ApprovedProducts/ucm304758.htm; http://www.fda.gov /downloads/BiologicsBloodVaccines/BloodBloodProducts /ApprovedProducts/LicensedProductsBLAs/UCM074923 .pdf). In 2013, AVA received market approval in the European Union (EU) using a 3-IM priming series and 3-yearly booster schedule (http://emergentbiosolutions.com/sites/default/files /BioThrax_Germany.pdf).These recent changes in the FDA-approved priming schedule and route of administration for AVA and EU approval of an alternate schedule warranted detailed characterization of their immunological impact. Serological noninferiority analyses for peak anti-PA IgG and lethal toxin neutralization activity (TNA) in response to the 3-IM priming schedule and alternative booster schedules were reported previously, and the safety profile of AVA administered IM in humans was confirmed to be similar to that for other alum-containing vaccines (4-6). Less frequent AVA injection doses resulted in a reduction in some injection site adverse events (AEs), and IM administration resulted in reduced frequency, duration, and severity of AEs (5-11). The potential for increasing the intervals between booster doses requires an assessment of sustained antibody functional activity, CMI, and the ability to develop rapid protective anamnestic responses (5,6,12).In a rhesus macaque model of inhalation anthrax, the AVA

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mentioning

confidence: 63%

Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

Quinn

Sabourin

Schiffer

et al. 2016

Clin Vaccine Immunol

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“…Data from Pittman et al showed higher antibody levels achieved with longer intervals between immunizations, and that antibody levels and the proportion of seroconverters were not compromised by longer intervals support such a schedule [24]. Pittman et al also showed that with the currently US used schedule anti PA levels peaked after the 4 th dose and the GM levels stayed above 80ug/ mL (the estimated protective level derived from experiments in rabbits) in all pre-vaccination assays [25]. Further doses brought back the levels to those achieved after the 4 th dose.…”

Section: Discussionmentioning

confidence: 99%

Serum IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel

Singer

Schneerson

Bautista

et al. 2008

Vaccine

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The seroconversion rates and geometric mean concentrations (GMC) of IgG anti-PA for stored sera from U.S. military personnel immunized 3, 4, and 6 times with the U.S. licensed anthrax vaccine adsorbed were studied. Anti-PA IgG concentrations were measured by ELISA. All 246 vaccinees had low but detectable pre-immunization anti-PA IgG (GMC 1.83μg/mL). Three doses elicited a GMC of 60 μg/mL and a seroconversion rate of 85.3%, four doses elicited a GMC of 157 μg/mL and 67.9% and the sixth of 277 μg/mL and 45.5% respectively. The forth dose elicited 100% seroconversion compared to the pre-immunization level. These results should facilitate comparison between different immunization schedules and new vaccines.

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“…Indeed, a recent study of antibody response in human volunteers injected with anthrax vaccine absorbed (AVA, BioThrax) found that the mean time to seroconversion was f27.7 days (range, 14-63 days; ref. 38). Moreover, it is apparent that the presence of adjuvant and formaldehyde in that vaccine contributes significantly to this response (39).…”

Section: Discussionmentioning

confidence: 99%

Anthrax Lethal Toxin Inhibits Growth of and Vascular Endothelial Growth Factor Release from Endothelial Cells Expressing the Human Herpes Virus 8 Viral G Protein–Coupled Receptor

Depeille¹,

Young²,

Boguslawski³

et al. 2007

Clinical Cancer Research

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Purpose: In this study, we tested the hypothesis that inhibition of mitogen-activated protein kinase kinases (MKK) inhibits tumor growth by acting on angiogenic signaling and by extension may form the basis of an effective strategy for treatment of Kaposi's sarcoma. Experimental Design: Murine endothelial cells expressing the human herpes virus 8 G protein–coupled receptor (vGPCR-SVEC) were treated with anthrax lethal toxin (LeTx). LeTx is a binary toxin ordinarily secreted by Bacillus anthracis and is composed of two proteins: protective antigen (the binding moiety) and lethal factor (the active moiety). Lethal factor is a protease that cleaves and inactivates MKKs. Results: In vitro, treatment of vGPCR-SVEC with LeTx inhibited MKK signaling, moderately inhibited cell proliferation, and blocked the ability of these cells to form colonies in soft agar. Treatment with LeTx also blocked the ability of these cells to release several angioproliferative cytokines, notably vascular endothelial growth factor (VEGF). In contrast, inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 with U0126 caused a substantial inhibition of proliferation but only modestly inhibited VEGF release. In xenograft models, i.v. injection of LeTx caused reduced tumor growth characterized immunohistochemically by inhibition of MKK signaling, decreased rates of proliferation, and reduced levels of VEGF and VEGF receptor 2, with a corresponding decrease in vascular density. Conclusions: These data support a role for MKK signaling in tumor growth and vascularization and are consistent with the hypothesis that inhibition of MKK signaling by LeTx or a similar agent may be an effective strategy for the treatment of Kaposi's sarcoma as well as other vascular tumors.

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Patterns of antibody response in humans to the anthrax vaccine adsorbed (AVA) primary (six-dose) series☆

Cited by 43 publications

References 25 publications

Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

Humoral and Cell-Mediated Immune Responses to Alternate Booster Schedules of Anthrax Vaccine Adsorbed in Humans

Serum IgG antibody response to the protective antigen (PA) of Bacillus anthracis induced by anthrax vaccine adsorbed (AVA) among U.S. military personnel

Anthrax Lethal Toxin Inhibits Growth of and Vascular Endothelial Growth Factor Release from Endothelial Cells Expressing the Human Herpes Virus 8 Viral G Protein–Coupled Receptor

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