Safety of anthrax vaccine: an expanded review and evaluation of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS)

Sever, John L.; Brenner, Alan I.; Gale, Arnold D.; Lyle, Jerry; Moulton, Lawrence H.; Ward, Brian J.; West, David J.

doi:10.1002/pds.936

Cited by 65 publications

(41 citation statements)

References 13 publications

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“…No mechanism for this activity has been proposed. Over 1.4 million people have been vaccinated with AVA, and studies have demonstrated the vaccine to be safe [32][33][34]. In spite of these facts, there remains significant resistance to AVA among military personnel and the public at large.…”

Section: Discussionmentioning

confidence: 99%

Domain specificity of the human antibody response to Bacillus anthracis protective antigen

Reason¹,

Ullal²,

Liberato³

et al. 2008

Vaccine

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Protective antigen (PA) is the cell surface recognition moiety of the Bacillus anthracis A-B toxin system, and the active immunogenic component in the currently licensed human anthrax vaccine (BioThrax™, or AVA). The serum antibody response to the PA protein is polyclonal and complex both in terms of the antibody combining sites utilized to bind PA and the PA-associated epitopes recognized. We have cloned, sequenced, and expressed a large panel of PA-specific human monoclonal antibodies from 7 AVA-immunized donors. Dot blots, Western blots, and radio-labeled antigen capture assays employing both proteolytic fragments of PA and engineered PA sub-domain fusion proteins were used to determine the region (domain) of the PA monomer to which each of the cloned human antibodies bound. The domain specificity of the isolated monoclonals was highly biased towards the amino-terminal 20kd fragment of PA (PA 20 ), with the majority (62%) of independently arising antibody clones reacting with determinants located on this PA fragment. A similar bias in domain specificity was also demonstrated in the serum response of AVA-vaccinated donors. Since PA 20 is cleaved from the remainder of the monomer rapidly following cell surface binding and has no known role in the intoxication process, the immunodominance of PA 20 -associated epitopes may directly affect the efficacy of PA-based anthrax vaccines.

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Section: Discussionmentioning

confidence: 99%

Domain specificity of the human antibody response to Bacillus anthracis protective antigen

Reason¹,

Ullal²,

Liberato³

et al. 2008

Vaccine

View full text Add to dashboard Cite

show abstract

“…Standardized survey instruments were used in the questionnaire for comparability. Sources included the Chicago Reproductive Health Survey (National Institute of Environmental Health Sciences, Research Triangle Park, NC, 1991), the National Survey on Family Growth, Cycle IV [42], and the National Maternal and Infant Health Survey [43]. Miscarriages/spontaneous abortions were defined as fetal deaths occurring before 22 weeks gestation, while stillbirths were defined as fetal deaths occurring after 22 weeks gestation.…”

Section: Study Populationmentioning

confidence: 99%

Self-Reported Reproductive Outcomes Among Male and Female 1991 Gulf War era US Military Veterans

Wells

Wang

Spooner

et al. 2006

Matern Child Health J

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“…This vaccine has been shown to confer good protection in humans (6), but it is a fairly undefined formulation and requires a 6-injection dosing regimen. Furthermore, there has been an ongoing debate about its safety, although large trials of the vaccine have indicated an acceptable safety level (7,8). As a result of these considerations, several approaches to a second generation vaccine are in development, the majority of which target PA.…”

mentioning

confidence: 99%

Immunogenicity and Protective Efficacy of Bacillus anthracis Poly-γ-d-glutamic Acid Capsule Covalently Coupled to a Protein Carrier Using a Novel Triazine-based Conjugation Strategy

Joyce

Cook

Chabot

et al. 2006

Journal of Biological Chemistry

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The capsular polypeptide of Bacillus anthracis is composed of a unique polyglutamic acid polymer in which D-glutamate monomers are joined by ␥-peptidyl bonds. The capsule is poorly immunogenic, and efforts at exploiting the polymer for vaccine development have focused on increasing its inherent immunogenicity through chemical coupling to immune-stimulating protein carriers. The usual strategy has employed carbodiimide-based condensing reagents for activation of free ␣-carboxyl groups, despite reports that this chemistry may lead to chain scission. We have purified the high molecular mass capsule to >95% homogeneity and have demonstrated that the polymer contains >99% poly-␥-D-glutamic acid. The predominant structure of the polymer as assessed by circular dichroism and multiangle laser light scattering was unordered at near-neutral pH. We investigated the effects of various activation chemistries, and we demonstrated that carbodiimide treatment under aqueous conditions results in significant cleavage of the ␥-peptidyl bond, whereas scission is significantly reduced in nonaqueous polar solvents, although undesired side chain modification was still observed. An activation chemistry was developed using the triazine-based reagent 4-(4,6-dimethoxy (1,3,5)triazin-2-yl)-4-methylmorpholinium chloride, which allowed for controlled and reproducible derivatization of ␣-carbonyls. In a two-pot reaction scheme, activated capsule was derivatized with a sulfhydryl-reactive heterobifunctional moiety and was subsequently coupled to thiolated carrier protein. This conjugate elicited very high capsule-specific immune titers in mice. More importantly, mice immunized with conjugated capsule exhibited good protection against lethal challenge from a virulent B. anthracis strain in two models of infection. We also showed, for the first time, that treatment of capsule with carbodiimide significantly reduced recognition by capsule-specific antisera concurrent with the reagent-induced reduction of polymer mass. The data suggested that for vaccine development, maintenance of the high mass of the polymer may be important.

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Safety of anthrax vaccine: an expanded review and evaluation of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS)

Cited by 65 publications

References 13 publications

Domain specificity of the human antibody response to Bacillus anthracis protective antigen

Domain specificity of the human antibody response to Bacillus anthracis protective antigen

Self-Reported Reproductive Outcomes Among Male and Female 1991 Gulf War era US Military Veterans

Immunogenicity and Protective Efficacy of Bacillus anthracis Poly-γ-d-glutamic Acid Capsule Covalently Coupled to a Protein Carrier Using a Novel Triazine-based Conjugation Strategy

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