scholarly journals Protective Immune Response against Bacillus anthracis Induced by Intranasal Introduction of a Recombinant Adenovirus Expressing the Protective Antigen Fused to the Fc-fragment of IgG2a

Acta Naturae ◽  
2014 ◽  
Vol 6 (1) ◽  
pp. 76-84 ◽  
Author(s):  
D. N. Shcherbinin ◽  
I. B. Esmagambetov ◽  
A. N. Noskov ◽  
Yu. O. Selyaninov ◽  
I. L. Tutykhina ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Recombinant Adenovirus ◽  
Antibody Fragment ◽  
Human Adenovirus ◽  
Skin Lesions ◽  
Aerobic Bacterium ◽  
Protective Properties ◽  
Fc Fragment

Anthrax is a particularly dangerous infectious disease that affects humans and livestock. It is characterized by intoxication, serosanguineous skin lesions, development of lymph nodes and internal organs, and may manifest itsself in either a cutaneous or septic form. The pathogenic agent is Bacillus anthracis, a grampositive, endospore-forming, rod-shaped aerobic bacterium. Efficacious vaccines that can rapidly induce a long-term immune response are required to prevent anthrax infection in humans. In this study, we designed three recombinant human adenovirus serotype-5-based vectors containing various modifications of the fourth domain of the B. anthracis protective antigen (PA). Three PA modifications were constructed: a secretable form (Ad-sPA), a non-secretable form (Ad-cPA), and a form with the protective antigen fused to the Fc fragment of immunoglobulin G2a (Ad-PA-Fc). All these forms exhibited protective properties against Bacillus anthracis. The highest level of protection was induced by the Ad-PA-Fc recombinant adenovirus. Our findings indicate that the introduction of the Fc antibody fragment into the protective antigen significantly improves the protective properties of the Ad-PA-Fc adenovirus against B. anthracis.

The Humoral Immune Response to Various Domains of Protective Antigen of Bacillus anthracis in Cutaneous Anthrax Cases in India

2016 ◽  
Vol 66 (6) ◽  
pp. 645 ◽  
Author(s):  
Anshul Varshney ◽  
Nidhi Puranik ◽  
M. Kumar ◽  
A.K. Goel
Keyword(s):  
Immune Response ◽  
Bacillus Anthracis ◽  
Humoral Immune Response ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Lethal Factor ◽  
Serum Samples ◽  
Public Health Importance ◽  
Humoral Immune ◽  
Cutaneous Anthrax

Anthrax, caused by Bacillus anthracis is known to occur globally since antiquity. Besides being an important biothreat agent, it is an important public health importance pathogen also in countries like India. B. anthracis secretes three distinct toxins, namely protective antigen (PA), lethal factor (LF) and edema factor (EF). PA is the central moiety of the anthrax toxin complex and therefore has been a molecule of choice for vaccine development. PA has four different domains with different functions. In this study, the major domains of PA were cloned and expressed in bacterial system. The purified recombinant proteins were used to determine the humoral immune response by ELISA using 43 human cutaneous anthrax serum samples. The maximum immunoreactivity was observed with the whole PA protein followed by domain 2, 4 and 1. The study corroborated that in addition to full PA, individual domain 2 and 4 can also be good target for vaccine development as well as for serodiagnostic assays for cutaneous anthrax

Immunogenicity and Biodistribution of Anthrax DNA Vaccine Delivered by Intradermal Electroporation

2020 ◽  
Vol 17 (5) ◽  
pp. 414-421
Author(s):  
Na Young Kim ◽  
Won Rak Son ◽  
Jun Young Choi ◽  
Chi Ho Yu ◽  
Gyeung Haeng Hur ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacillus Anthracis ◽  
Dna Vaccine ◽  
Fluorescent Protein ◽  
Protective Antigen ◽  
Dna Vaccines ◽  
Bacterial Disease ◽  
Intradermal Administration ◽  
Bacterium Bacillus

Purpose: Anthrax is a lethal bacterial disease caused by gram-positive bacterium Bacillus anthracis and vaccination is a desirable method to prevent anthrax infections. In the present study, DNA vaccine encoding a protective antigen of Bacillus anthracis was prepared and we investigated the influence of DNA electrotransfer in the skin on the induced immune response and biodistribution. Methods and Results: The tdTomato reporter gene for the whole animal in vivo imaging was used to assess gene transfer efficiency into the skin as a function of electrical parameters. Compared to that with 25 V, the transgene expression of red fluorescent protein increased significantly when a voltage of 90 V was used. Delivery of DNA vaccines expressing Bacillus anthracis protective antigen domain 4 (PAD4) with an applied voltage of 90 V induced robust PA-D4-specific antibody responses. In addition, the in vivo fate of anthrax DNA vaccine was studied after intradermal administration into the mouse. DNA plasmids remained at the skin injection site for an appropriate period of time after immunization. Intradermal administration of DNA vaccine resulted in detection in various organs (viz., lung, heart, kidney, spleen, brain, and liver), although the levels were significantly reduced. Conclusion: Our results offer important insights into how anthrax DNA vaccine delivery by intradermal electroporation affects the immune response and biodistribution of DNA vaccine. Therefore, it may provide valuable information for the development of effective DNA vaccines against anthrax infection.

scholarly journals HLA class II polymorphism influences the immune response to protective antigen and susceptibility to Bacillus anthracis

2019 ◽  
Author(s):  
Stephanie Ascough ◽  
Rebecca J. Ingram ◽  
Karen K. Y. Chu ◽  
Stephen J. Moore ◽  
Theresa Gallagher ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
T Cell Responses ◽  
Class Ii ◽  
Hla Class Ii ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Immunodominant Epitopes

AbstractThe causative agent of anthrax, Bacillus anthracis, evades the host immune response and establishes infection through the production of binary exotoxins composed of Protective Antigen (PA) and one of two subunits, lethal factor (LF) or edema factor (EF). The majority of vaccination strategies have focused upon the antibody response to the PA subunit. We have used a panel of humanised HLA class II transgenic mouse strains to define HLA-DR-restricted and HLA-DQ-restricted CD4+ T cell responses to the immunodominant epitopes of PA. This was correlated with the binding affinities of epitopes to HLA class II molecules, as well as the responses of two human cohorts: individuals vaccinated with the Anthrax Vaccine Precipitated (AVP) vaccine (which contains PA and trace amounts of LF), and patients recovering from cutaneous anthrax infections. The infected and vaccinated cohorts expressing different HLA types were found to make CD4+ T cell responses to multiple and diverse epitopes of PA. The effects of HLA polymorphism were explored using transgenic mouse lines, which demonstrated differential susceptibility, indicating that HLA-DR1 and HLA-DQ8 alleles conferred protective immunity relative to HLA-DR15, HLA-DR4 and HLA-DQ6. The HLA transgenics enabled a reductionist approach, allowing us to better define CD4+ T cell epitopes. Appreciating the effects of HLA polymorphism on the variability of responses to natural infection and vaccination will be vital in planning protective strategies against anthrax.Author SummaryThe bacterium responsible for causing the disease anthrax, Bacillus anthracis, produces a binary toxin composed of Protective Antigen (PA) and either Lethal Factor (LF) or Edema Factor (EF). Previous vaccination strategies have focused upon the antibody response to the PA subunit. However, within the field of bacterial immunity, there is a growing appreciation of the importance of the adaptive immune response, specifically led by CD4+ T cells. We identified long-term CD4+ T cell responses to PA epitopes following cutaneous human anthrax infection and vaccination, indicating that this toxin component is a principle B. anthracis antigen. To characterise the impact of polymorphism in HLA class II alleles at DR and DQ loci, we used transgenic mice to map the immunodominant epitopes from PA. This was correlated with survival in the transgenic lines following live anthrax challenge. We were able to demonstrate the differential impact of HLA class II alleles upon the CD4+ T cell immunodominant epitopes which shaped the immune hierarchy and therefore susceptibility to anthrax infection.

scholarly journals Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax

2015 ◽  
Vol 22 (8) ◽  
pp. 902-908 ◽  
Author(s):  
Zhaochun Chen ◽  
Rachel Schneerson ◽  
Julie A. Lovchik ◽  
Zhongdong Dai ◽  
Joanna Kubler-Kielb ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Polyclonal Antibodies ◽  
Secondary Immune Response ◽  
Lethal Challenge ◽  
Content Type ◽  
Antibody Titers ◽  
Opsonophagocytic Killing ◽  
Anthrax Vaccines

ABSTRACTThe immunogenicity ofBacillus anthraciscapsule (poly-γ-d-glutamic acid [PGA]) conjugated to recombinantB. anthracisprotective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >103were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 103. An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ≤300, with the antibodies peaking above 104following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing ofB. anthracis. Most important, the PGA-TT–induced antibodies protected mice from a lethal challenge with virulentB. anthracisspores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines.

scholarly journals PERSPECTIVES OF DEVELOPMENT OF LIVE RECOMBINANT ANTHRAX VACCINES BASED ON OPPORTUNISTIC AND APATHOGENIC MICROORGANISMS

2016 ◽  
pp. 79-89
Author(s):  
P. Yu. Popova ◽  
N. I. Mikshis
Keyword(s):  
Immune Response ◽  
Genetic Engineering ◽  
Bacillus Anthracis ◽  
Direct Contact ◽  
Systemic Immune Response ◽  
Protective Properties ◽  
Mucous Membranes ◽  
Boost Immunization ◽  
Anthrax Vaccines

Live genetic engineering anthrax vaccines on the platform of avirulent and probiotic micro-ogranisms are a safe and adequate alternative to preparations based on attenuated Bacillus anthracis strains. Mucosal application results in a direct contact of the vaccine preparations with mucous membranes in those organs and tissues of the macro-organisms, that are exposed to the pathogen in the first place, resulting in a development of local and systemic immune response. Live recombinant anthrax vaccines could be used both separately as well as in a prime-boost immunization scheme. The review focuses on immunogenic and protective properties of experimental live genetic engineering preparations, created based on members ofgeni of Salmonella, Lactobacillus and adenoviruses.

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