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Showing papers on "Anthrax vaccines published in 2014"


Journal ArticleDOI
TL;DR: The combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.
Abstract: Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax adjuvant afforded significantly greater protection against aerosolized Bacillus anthracis Sterne strain 7702 than three immunizations with PA alone. Murabutide had a weaker adjuvant effect than Advax when used alone, but when murabutide was formulated together with Advax, an additive effect on immunogenicity and protection was observed, with complete protection after just two doses. The combined adjuvant formulation stimulated a robust, long-lasting B-cell memory response that protected mice against an aerosol challenge 18 months postimmunization with acceleration of the kinetics of the anamnestic IgG response to B. anthracis as reflected by ∼4-fold-higher anti-PA IgG titers by day 2 postchallenge versus mice that received PA with Alhydrogel. In addition, the combination of Advax plus murabutide induced approximately 3-fold-less inflammation than Alhydrogel as measured by in vivo imaging of cathepsin cleavage resulting from injection of ProSense 750. Thus, the combination of Advax and murabutide provided enhanced protection against inhalational anthrax with reduced localized inflammation, making this a promising next-generation anthrax vaccine adjuvanting strategy.

50 citations


Journal ArticleDOI
TL;DR: This study examines the feasibility of oral PA vaccine expressed in an edible plant system against anthrax by expressing protective antigen (PA) gene in Indian mustard by Agrobacterium-mediated transformation and in tobacco by plastid transformation.

45 citations


Journal ArticleDOI
TL;DR: This document provides clinical guidance for the prophylaxis and treatment of neonates, infants, children, adolescents, and young adults up to the age of 21 in the event of a deliberate B anthracis release and offers guidance in areas where the unique characteristics of children dictate a different clinical recommendation from adults.
Abstract: Anthrax is a zoonotic disease caused by Bacillus anthracis, which has multiple routes of infection in humans, manifesting in different initial presentations of disease. Because B anthracis has the potential to be used as a biological weapon and can rapidly progress to systemic anthrax with high mortality in those who are exposed and untreated, clinical guidance that can be quickly implemented must be in place before any intentional release of the agent. This document provides clinical guidance for the prophylaxis and treatment of neonates, infants, children, adolescents, and young adults up to the age of 21 (referred to as “children”) in the event of a deliberate B anthracis release and offers guidance in areas where the unique characteristics of children dictate a different clinical recommendation from adults.

44 citations


Journal ArticleDOI
TL;DR: Humoral and cell-mediated immune correlates of protection (COP) for inhalation anthrax in a rhesus macaque (Macaca mulatta) model were determined and the anti-PA IgG levels and lethal toxin neutralization activity (TNA) and the frequency of gamma interferon (IFN-γ)-secreting cells at month 6 had statistically significant positive correlations with survival.
Abstract: Humoral and cell-mediated immune correlates of protection (COP) for inhalation anthrax in a rhesus macaque (Macaca mulatta) model were determined. The immunological and survival data were from 114 vaccinated and 23 control animals exposed to Bacillus anthracis spores at 12, 30, or 52 months after the first vaccination. The vaccinated animals received a 3-dose intramuscular priming series (3-i.m.) of anthrax vaccine adsorbed (AVA) (BioThrax) at 0, 1, and 6 months. The immune responses were modulated by administering a range of vaccine dilutions. Together with the vaccine dilution dose and interval between the first vaccination and challenge, each of 80 immune response variables to anthrax toxin protective antigen (PA) at every available study time point was analyzed as a potential COP by logistic regression penalized by least absolute shrinkage and selection operator (LASSO) or elastic net. The anti-PA IgG level at the last available time point before challenge (last) and lymphocyte stimulation index (SI) at months 2 and 6 were identified consistently as a COP. Anti-PA IgG levels and lethal toxin neutralization activity (TNA) at months 6 and 7 (peak) and the frequency of gamma interferon (IFN-γ)-secreting cells at month 6 also had statistically significant positive correlations with survival. The ratio of interleukin 4 (IL-4) mRNA to IFN-γ mRNA at month 6 also had a statistically significant negative correlation with survival. TNA had lower accuracy as a COP than did anti-PA IgG response. Following the 3-i.m. priming with AVA, the anti-PA IgG responses at the time of exposure or at month 7 were practicable and accurate metrics for correlating vaccine-induced immunity with protection against inhalation anthrax.

39 citations


Journal ArticleDOI
28 Nov 2014-Vaccine
TL;DR: In this article, a phase-I clinical trial was conducted to confirm biomarkers of innate immunity and evaluate effects of CPG 7909 (PF-03512676) on adaptive immunity.

21 citations


Journal ArticleDOI
TL;DR: A culture-independent method of diagnosing anthrax through the use of monoclonal antibodies to detect PA and LF in the lethal toxin complex is demonstrated.

16 citations


Journal ArticleDOI
TL;DR: This research successfully inserted the 2β2-2β3 loop of PA into the major immunodominant region (MIR) of hepatitis B virus core (HBc) protein, and removed amino acids 79-81 from the HBc MIR of theHBcL2, leading to the full protection of the immunized mice against a lethal dose anthrax toxin challenge.

16 citations


Journal ArticleDOI
Sharad Mangal, Dilip Pawar1, Udita Agrawal, Arvind K. Jain, Suresh P. Vyas 
TL;DR: A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax and resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response.
Abstract: The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was − 29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

15 citations


Journal ArticleDOI
TL;DR: This document provides a summary of the guidance contained in the clinical report for diagnosis and management of anthrax, including antimicrobial treatment and postexposure prophylaxis (PEP), use of antitoxin, and recommendations for use of Anthrax vaccine in neonates, infants, children, adolescents, and young adults up to the age of 21 years.
Abstract: * Abbreviations: AVA — : anthrax vaccine adsorbed CDC — : Centers for Disease Control and Prevention PEP — : postexposure prophylaxis The use of Bacillus anthracis as a biological weapon is considered a potential national security threat by the US government. B anthracis has the ability to be used as a biological weapon and to cause anthrax, which can rapidly progress to systemic disease with high mortality in those who are untreated. Therefore, clear plans for managing children after a B anthracis bioterror exposure event must be in place before any intentional release of the agent. This document provides a summary of the guidance contained in the clinical report (appendices cited in this executive summary refer to those in the clinical report) for diagnosis and management of anthrax, including antimicrobial treatment and postexposure prophylaxis (PEP), use of antitoxin, and recommendations for use of anthrax vaccine in neonates, infants, children, adolescents, and young adults up to the age of 21 years (referred to as “children”). Key considerations in a mass B anthracis exposure scenario include the following: 1. Public health authorities will determine the presence and extent of a bioterror event. Information of importance to health care providers and the public will be made available as soon as possible by the Centers for Disease Control and Prevention (CDC), including information posted on the CDC Anthrax Web site: www.cdc.gov/anthrax. 2. Within 48 hours of exposure to B anthracis spores, public health authorities plan to provide a 10-day course of antimicrobial prophylaxis to the local population, including children likely to have been exposed to spores (Appendix 1). Public health officials will provide information about points of dispensing locations that will distribute antibiotic agents. 3. Within 10 days of exposure, public health authorities plan to further define those who have had a clear and significant exposure and will require an additional 50 days of antimicrobial PEP, …

13 citations


Journal ArticleDOI
TL;DR: It is shown here that exposure to anthrax in this manner elicits strong T cell immunity, even in the face of extremely severe disease, contrary to expectation when one considers the well-documented ablative effect of anthrax toxins on immune function.

11 citations


Journal ArticleDOI
TL;DR: It is largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.
Abstract: Developing an effective anthrax vaccine that can induce a rapid and sustained immune response is a priority for the prevention of bioterrorism-associated anthrax infection. Here, we developed a recombinant replication-deficient adenovirus serotype 5-based vaccine expressing the humanized protective antigen (Ad5-PAopt). A single intramuscular injection of Ad5-PAopt resulted in rapid and robust humoral and cellular immune responses in Fisher 344 rats. Animals intramuscularly inoculated with a single dose of 10⁸ infectious units of Ad5-PAopt achieved 100% protection from challenge with 10 times the 50% lethal dose (LD₅₀) of anthrax lethal toxin 7 days after vaccination. Although preexisting intranasally induced immunity to Ad5 slightly weakened the humoral and cellular immune responses to Ad5-PAopt via intramuscular inoculation, 100% protection was achieved 15 days after vaccination in Fisher 344 rats. The protective efficacy conferred by intramuscular vaccination in the presence of preexisting intranasally induced immunity was significantly better than that of intranasal delivery of Ad5-PAopt and intramuscular injection with recombinant PA and aluminum adjuvant without preexisting immunity. As natural Ad5 infection often occurs via the mucosal route, the work here largely illuminates that intramuscular inoculation with Ad5-PAopt can overcome the negative effects of immunity induced by prior adenovirus infection and represents an efficient approach for protecting against emerging anthrax.

Journal ArticleDOI
29 Oct 2014-Vaccine
TL;DR: Depending on the extent of the outbreak, effectiveness of antibiotics and availability of vaccine, the full dose 0, 28 or 0, 14, 28 schedules may have advantages.

Journal ArticleDOI
13 Aug 2014-Toxins
TL;DR: The data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response.
Abstract: Anthrax Vaccine Adsorbed (AVA) generates short-lived protective antigen (PA) specific IgG that correlates with in vitro toxin neutralization and protection from Bacillus anthracis challenge. Animal studies suggest that when PA-specific IgG has waned, survival after spore challenge correlates with an activation of PA-specific memory B cells. Here, we characterize the quantity and the longevity of AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells (PBMCs) from individuals vaccinated ≥3 times with AVA (n = 50) were collected early (3-6 months, n = 27) or late after their last vaccination (2-5 years, n = 23), pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B cells differentiated into antibody secreting cells (ASCs). PA-specific ASC percentages ranged from 0.02% to 6.25% (median: 1.57%) and did not differ between early and late post-vaccination individuals. PA-specific ASC percentages correlated with plasma PA-specific IgG (r = 0.42, p = 0.03) and toxin neutralization (r = 0.52, p = 0.003) early post vaccination. PA-specific ASC percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001) and late post vaccination (r = 0.71, p < 0.0001). These data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response.

Journal ArticleDOI
03 Sep 2014-Vaccine
TL;DR: Providing a missed AVA dose after a delay as long as 5-7 years, elicits anti-PA IgG antibody and TNA ED50 responses that are robust and non-inferior to the responses observed when the 6-month dose is given on-schedule.

Journal ArticleDOI
TL;DR: This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells, and results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination.
Abstract: Anthrax is caused by the spore-forming bacterium Bacillus anthracis, which has been used as a weapon for bioterrorism. Although current vaccines are effective, they involve prolonged dose regimens and often cause adverse reactions. High rates of mortality associated with anthrax have made the development of an improved vaccine a top priority. To identify novel vaccine candidates, we applied an immunoproteomics approach. Using sera from convalescent guinea pigs or from human patients with anthrax, we identified 34 immunogenic proteins from the virulent B. anthracis H9401. To evaluate vaccine candidates, six were expressed as recombinant proteins and tested in vivo. Two proteins, rGBAA_0345 (alkyl hydroperoxide reductase subunit C) and rGBAA_3990 (malonyl CoA-acyl carrier protein transacylase), have afforded guinea pigs partial protection from a subsequent virulent-spore challenge. Moreover, combined vaccination with rGBAA_0345 and rPA (protective antigen) exhibited an enhanced ability to protect against anthrax mortality. Finally, we demonstrated that GBAA_0345 localizes to anthrax spores and bacilli. Our results indicate that rGBAA_0345 may be a potential component of a multivalent anthrax vaccine, as it enhances the efficacy of rPA vaccination. This is the first time that sera from patients with anthrax have been used to interrogate the proteome of virulent B. anthracis vegetative cells.

Journal ArticleDOI
TL;DR: Evidence that vaccine strain of Bacillus anthracis was gram-positive rod-shaped bacteria appeared as single to short-chained bacilli with blunted ends and anthrax vaccine bacteria were sensitive to penicillin, streptomycin, amoxicillin and kenamycin is provided.
Abstract: Anthrax is a zoonotic disease caused by the bacterium Bacillus anthracis that normally affects animals, especially ruminants (such as cattle, goats, sheep, and horses) and humans. This study was planned to characterize the morphology of anthrax vaccine bacteria by using Gram’s stain, polychrome methylene blue stain, culture on nutrient agar and nutrient broth media and to determine the immunological status of this vaccine by indirect ELISA and slide agglutination test in cattle. Antibiotic sensitivity test of vaccine strain of bacteria was also done. This study provided evidence that vaccine strain of Bacillus anthracis was gram-positive rod-shaped bacteria appeared as single to short-chained bacilli with blunted ends. Serum from anthrax vaccinated cattle agglutinated anthrax antigen on Day 30 (+++ within 5 min and ++ within 7 min at 1:100 dilution of test sera) and Day 90 (+++ within 5 min at 1:100 dilution of test sera) of post immunization. Immunization of cattle with anthrax vaccine generated high level of anti-anthrax IgG antibody response at Day 30 (0.789}0.014) of post immunization and reached its peak at Day 90 (0.991}0.047). This study also provided evidence that anthrax vaccine bacteria were sensitive to penicillin, streptomycin, amoxicillin and kenamycin. It may be recommended that the anthrax vaccine currently in use in Bangladesh is proved to be effective in term of morphology of Bacillus antharis and raising anti anthrax IgG antibody response in cattle with no side effect. DOI: http://dx.doi.org/10.3329/bjvm.v11i1.17732 Bangl. J. Vet. Med. (2013). 11 (1): 43-49

Journal ArticleDOI
TL;DR: After vaccination, immunological response was found in goat, however whether this immune response can protect natural anthrax infection need to be evaluated through challenge dose of fields isolates of Bacillus anthracis in future.
Abstract: Anthrax is caused by Bacillus anthracis bacterium and an acute infectious febrile septicemic disease of all warm-blooded animals including human. It is a disease of major economic importance in ruminant specially in goat characterized principally by a rapid fatal course followed by sudden death. The present investigation was under taken to determine the biochemical characterization of anthrax spore vaccine bacteria and to determine the immunological response in goat after anthrax vaccination. Anthrax vaccine was collected from local government veterinary hospital, Mymensingh which was prepared by LRI. The goats were selected from different regions of Bangladesh. The used methods were culture of vaccine bacterial sediment in different media, staining of bacteria with Gram’s stain, and sugar fermentation tests for biochemical characterization of anthrax vaccine bacteria. Slide agglutination test and indirect ELISA tests were performed for immunological response after vaccination. Morphologically anthrax vaccine bacteria was gram positive rod shaped or short chain in anthrax vaccine sediment, culture in nutrient agar and nutrient broth. The anthrax vaccine bacteria fermented three sugars (dextrose, maltose and sucrose) and produced only acid but did not ferment two sugars (lactose and mannitol). Immunuglobulin of collected serum (Day0, Day30 and Day90) also agglutinated anthrax antigen on Day 30 and Day 90 of post immunization and onwards. Indirect ELISA provided evidence that immunization of captive and free range goat generated level of anti anthrax 1gG antibody response at Day 0 (OD Value 0.5474±0.0466) of immunization and reached its peak at Day 30 (OD Value 0.9604±0.0936) and maintained that level up to the end of the study (Day 90, OD Value 1.217±0.1129). After vaccination, immunological response was found in goat. However whether this immune response can protect natural anthrax infection need to be evaluated through challenge dose of fields isolates of Bacillus anthracis in future. DOI: http://dx.doi.org/10.3329/bjvm.v11i2.19140 Bangl. J. Vet. Med . (2013).11(2): 151-157