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Anthrax Vaccine (anthrax + vaccine)
Selected AbstractsAnthrax vaccine powder formulations for nasal mucosal deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2006Ge Jiang Abstract Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6,8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7,8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:80,96, 2006 [source] Evaluation of the immune response induced by a nasal anthrax vaccine based on the protective antigen protein in anaesthetized and non-anaesthetized miceJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2006Brian R. Sloat To better protect against inhalational anthrax infection, a nasal anthrax vaccine based on the protective antigen (PA) protein of Bacillus anthracis could be an attractive alternative to the current Anthrax-Vaccine-Adsorbed (AVA), which was licensed for cutaneous anthrax prevention. Previously, we have demonstrated that an anti-PA immune response comparable with that in mice subcutaneously immunized with PA protein adjuvanted with aluminium hydroxide was induced in both the systemic compartment and the mucosal secretions of the nose and lung of anaesthetized mice when they were nasally immunized with PA protein incorporated into previously reported LPD (Liposome,Protamine,DNA) particles. In this study, we evaluated the anti-PA immune response induced by the nasal PA/LPD particles in non-anaesthetized mice and compared it with that in anaesthetized mice. Our data showed that the anti-PA antibody response and the anthrax lethal toxin-neutralization activity induced by the nasal PA/LPD in non-anaesthetized mice was relatively weaker than that in anaesthetized mice. However, the splenocytes isolated from the nasally immunized mice, anaesthetized and non-anaesthetized, proliferated comparably after in-vitro re-stimulation. By evaluating the uptake of fluorescence-labelled LPD particles by phagocytes in the nasal and broncho-alveolar lavages of mice after the nasal administration, we concluded that the relatively weaker anti-PA immune response in the non-anaesthetized mice might be partially attributed to the reduced retention of the PA/LPD particles in the nasal cavity of the non-anaesthetized mice. Data collected in this study are expected to be useful for future anthrax nasal vaccine studies when mice are used as a model. [source] Evaluation of body mass index, pre-vaccination serum progesterone levels and anti-anthrax protective antigen immunoglobulin G on injection site adverse events following anthrax vaccination in womenPHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 11 2008Yujia Zhang PhD Abstract Background In 2002, CDC initiated the Anthrax Vaccination Program (AVP) to provide voluntary pre-exposure anthrax vaccination for individuals at high risk for exposure to Bacillus anthracis spores. The AVP offered an opportunity to investigate hypothesized reasons for a reported gender difference in injection site adverse events (AEs) following anthrax vaccine adsorbed (AVA). Objectives To evaluate in women the impact of body mass index (BMI), pre-vaccination serum progesterone levels, and pre-vaccination anti-anthrax protective antigen immunoglobulin G concentrations (anti-PA IgG) on the occurrence of AEs following subcutaneous AVA vaccination. Methods Participants' BMI was determined at enrollment. Also, pre-vaccination blood samples were assayed for serum progesterone and anti-PA IgG. Post-vaccination solicited AEs were recorded by participants using a 4-day diary card. Results Obese group had an elevated risk for arm soreness. Decreased pre-vaccination serum progesterone level was associated with arm swelling. Increased pre-vaccination anti-PA IgG was associated with itching on the arm; and within the obese group, was associated with arm swelling, lump or knot, redness, soreness, and warmth. Conclusions In AVA vaccinated women, obesity was associated with arm soreness and decreased pre-vaccination serum progesterone levels were associated with increased rate of arm swelling. Increased pre-vaccination anti-PA IgG may be associated with an increased frequency of itching on the arm, and in obese women, may increase the occurrence of arm swelling, lump or knot, redness, and warmth. Administering AVA according to a woman's menstrual phase may reduce the occurrence of certain injection site reactions. Copyright © 2008 John Wiley & Sons, Ltd. [source] Assessment of anthrax vaccination data in the Defense Medical Surveillance System, 1998,2004,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2007Daniel C. Payne PhD MSPH Abstract Purpose Understanding the completeness and accuracy of U.S. military anthrax vaccination data is important to the design and interpretation of studies to assess the safety of anthrax vaccine. We estimated the agreement between electronically recorded anthrax vaccination data in the Defense Medical Surveillance System (DMSS) versus anthrax vaccination data abstracted from hardcopy medical charts in a representative sample of the U.S. military from 1998 to 2004. Methods Medical chart abstractions were conducted at 28 military treatment facilities for 4201 personnel. Abstracted anthrax vaccination data for 1817 personnel, representing 7400 anthrax vaccine doses, were compared with electronically captured data in the DMSS from 1998 to 2004. Sensitivity, positive predictive value (PPV), specificity and negative predictive value (NPV) were calculated using weighted analyses. Results Weighted person-level analysis revealed DMSS sensitivity,=,93.8% (95%CI,=,91.1, 95.8), specificity,=,87.0% (79.0, 92.3), PPV,=,85.6% (77.2, 91.3) and NPV,=,94.5% (91.7, 96.4). Report of anthrax vaccination within a ±7 days window in both medical chart and DMSS electronic data had a sensitivity of 88.3% (85.4, 90.7) and a PPV of 86.6% (84.9, 88.2) in the vaccine dose-level analysis. Conclusions These results support that anthrax vaccination data captured by the DMSS are adequate for post-marketing surveillance investigations in the U.S. military and are of comparable quality to data captured by other vaccine safety databases. Copyright © 2007 John Wiley & Sons, Ltd. [source] Short-term reactogenicity and gender effect of anthrax vaccine: analysis of a 1967,1972 study and review of the 1955,2005 medical literature,,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2007Michael M. McNeil MD Abstract Purpose In the 1960s, the Centers for Disease Control and Prevention (CDC) held the investigational new drug (IND) application for the anthrax vaccine and collected short-term safety data from approximately 16,000 doses administered to almost 7000 individuals. While some recent anthrax vaccine safety studies have suggested that women experience more injection site reactions (ISRs), to our knowledge the IND safety data were not previously examined for a gender-specific difference. Methods We identified and analyzed a subset of the IND study data representing a total of 1749 persons who received 3592 doses from 1967 to 1972. Original data collection forms were located and information extracted, including: vaccine recipient's name, age at vaccination, gender, dose number, date of vaccination, lot number, grading of ISR, presence and type of systemic reactions. Overall and gender-specific rates for adverse reactions to anthrax vaccine were calculated and we performed a multivariable analysis. Results We found an ISR was associated with 28% of anthrax vaccine doses; however, 87% of these were considered mild. Systemic reactions were uncommon (<1%) and most (70%) accompanied an ISR. Our dose-specific analysis by gender found women had at least twice the risk of having a vaccine reaction compared to men. Our age-adjusted relative risk for ISR in women compared to men was 2.78 (95%CI: 2.29, 3.38). Conclusions Our results for both overall and gender-specific reactogenicity are consistent with other anthrax safety studies. To date, possible implications of these gender differences observed for anthrax and other vaccines are unknown and deserve further study. Copyright © 2007 John Wiley & Sons, Ltd. [source] Safety of anthrax vaccine: an expanded review and evaluation of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS),,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 12 2004John L. Sever Abstract Purpose To assess the safety of a licensed anthrax vaccine (AVA) given to more than 500,000 US military personnel, through review and medical evaluation of adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS). Methods AEs were summarized by person, vaccine lot, type, frequency and impact. A Delphic approach was used to tentatively assess causality in an effort to detect serious AEs (SAEs) or other medically important AEs (OMIAEs) possibly attributable to AVA. Results The Anthrax Vaccine Expert Committee (AVEC) reviewed 1841 reports describing 3991 AEs (9.4 reports/10,000 doses of AVA) that were submitted to VAERS from 1Q1998 through 4Q2001. One hundred forty-seven reports described an SAE or OMIAE, of which 26 were tentatively rated as possible, probable or certain consequences of vaccination (injection-site reaction [12], ,anaphylactic-like reaction' [5] and eight other systemic AEs [1,2 each]). Conclusions This review produced no evidence for an unusual rate of any SAE or OMIAE attributable to AVA. It supported an earlier impression that AVA may cause significant local inflammation and should be administered over the deltoid rather than the triceps to avoid direct or compression injury to the ulnar nerve. The subjects of VAERS reports tended to be older than all recipients of AVA. Females generally had and/or reported AEs more often than males, but transient articular reactions were surprisingly more common in males. Variations in the frequency or severity (as judged by hospitalization and/or loss of duty) of reported AEs did not suggest a significant problem with (1) a particular lot of AVA, (2) recurrent AEs after multiple doses or (3) vaccination of persons with a concomitant illness or those given other vaccines or medications. Copyright © 2004 John Wiley & Sons, Ltd. [source] Safety of anthrax vaccine: a review by the Anthrax Vaccine Expert Committee (AVEC) of adverse events reported to the Vaccine Adverse Event Reporting System (VAERS)PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 3 2002John L. Sever Abstract Purpose To assess the safety of a licensed anthrax vaccine given to nearly 400,000 US military personnel, reports of adverse events (AEs) submitted to the Vaccine Adverse Event Reporting System (VAERS) were reviewed and evaluated medically. Methods The Anthrax Vaccine Expert Committee (AVEC), a civilian panel of private-sector physicians and other scientists, reviewed 602 VAERS reports using a Delphic approach (structured expert consensus) to assess the causal relationship between vaccination and the reported AEs and sought to identify unexpected patterns in the occurrence of medically important events. Reports were entered into a database and used to profile AEs with respect to person, type/location, relative frequency, severity/impact, concomitant illness or receipt of other drugs or vaccines, and vaccine lot. Results Nearly half the reports noted a local injection-site AE, with more than one-third of these involving a moderate to large degree of inflammation. Six events qualified as serious AEs (SAEs), and all were judged to be certain consequences of vaccination. Three-quarters of the reports cited a systemic AE (most common: flu-like symptoms, malaise, rash, arthralgia, headache), but only six individual medically important events were judged possibly or probably due to vaccine (aggravation of spondyloarthropathy (2), anaphylactoid reaction, arthritis (2), bronchiolitis obliterans organizing pneumonia) Conclusions Since some cases of local inflammation involved distal paresthesia, AVEC recommends giving subcutaneous injections of AVA over the inferior deltoid instead of the triceps to avoid compression injury to the ulnar nerve. At this time, ongoing evaluation of VAERS reports does not suggest a high frequency or unusual pattern of serious or other medically important AEs. Copyright © 2002 John Wiley & Sons, Ltd. [source] | ||||||||||