Construction of a bivalent vaccine against anthrax and smallpox using the attenuated vaccinia virus KVAC103

Abstract Background Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases, we constructed a bivalent vaccine against both anthrax and smallpox by integrating a gene encoding protective antigen (PA) of Bacillus anthracis to the genome of the attenuated vaccinia virus strain, KVAC103. Results Immunization with this bivalent vaccine induced antibodies against both PA and vaccinia virus in a mouse model. We also observed that the efficacy of this vaccine can be enhanced by combined immunization with immunoadjuvant-expressing KVAC103. Mouse groups co-immunized with PA-expressing KVAC103 and either interleukin-15 (IL-15) or cholera toxin subunit A (CTA1)-expressing KVAC103 showed increased anti-PA IgG titer and survival rate against B. anthracis spore challenge compared to the group immunized with PA-expressing KVAC103 alone. Conclusions We demonstrated that the attenuated smallpox vaccine KVAC103 is an available platform for a multivalent vaccine and co-immunization of immunoadjuvants can improve vaccine performance.

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Construction of a bivalent vaccine against anthrax and smallpox using the attenuated vaccinia virus KVAC103

10.21203/rs.3.rs-61514/v2 ◽

2020 ◽

Author(s):

Deok Bum Park ◽

Bo-Eun Ahn ◽

Ho Sun Son ◽

Young-Ran Lee ◽

Yu-Ri Kim ◽

...

Keyword(s):

Survival Rate ◽

High Risk ◽

Mouse Model ◽

Infectious Diseases ◽

Vaccinia Virus ◽

Protective Antigen ◽

Gene Encoding ◽

Bivalent Vaccine ◽

Interleukin 15 ◽

Vaccinia Virus Strain

Abstract Background: Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases, we constructed a bivalent vaccine against both anthrax and smallpox by integrating a gene encoding protective antigen (PA) of Bacillus anthracis to the genome of the attenuated vaccinia virus strain, KVAC103.Results: Immunization with this bivalent vaccine induced antibodies against both PA and vaccinia virus in a mouse model. We also observed that the efficacy of this vaccine can be enhanced by combined immunization with immunoadjuvant-expressing KVAC103. Mouse groups co-immunized with PA-expressing KVAC103 and either interleukin-15 (IL-15) or cholera toxin subunit A (CTA1)-expressing KVAC103 showed increased anti-PA IgG titer and survival rate against B. anthracis spore challenge compared to the group immunized with PA-expressing KVAC103 alone.Conclusions: We demonstrated that the attenuated smallpox vaccine KVAC103 is an available platform for a multivalent vaccine and co-immunization of immunoadjuvants can improve vaccine performance.

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Construction of A Bivalent Vaccine Against Anthrax and Smallpox Using The Attenuated Vaccinia Virus KVAC103

10.21203/rs.3.rs-61514/v1 ◽

2020 ◽

Author(s):

Deok Bum Park ◽

Bo-Eun Ahn ◽

Ho Sun Son ◽

Young-Ran Lee ◽

Yu-Ri Kim ◽

...

Keyword(s):

Survival Rate ◽

High Risk ◽

Mouse Model ◽

Infectious Diseases ◽

Vaccinia Virus ◽

Protective Antigen ◽

Gene Encoding ◽

Bivalent Vaccine ◽

Interleukin 15 ◽

Vaccinia Virus Strain

Abstract Background: Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases, we constructed a bivalent vaccine against both anthrax and smallpox by integrating a gene encoding protective antigen (PA) of Bacillus anthracis to the genome of the attenuated vaccinia virus strain, KVAC103. Results: Immunization with this bivalent vaccine induced antibodies against both PA and vaccinia virus in a mouse model. We also observed that the efficacy of this vaccine can be enhanced by combined immunization with immunoadjuvant-expressing KVAC103. Mice groups co-immunized with PA-expressing KVAC103 and either interleukin-15 (IL-15) or cholera toxin subunit A (CTA1)-expressing KVAC103 showed increased anti-PA IgG titer and survival rate against B. anthracis spore challenge compared to the group immunized with PA-expressing KVAC103 alone. Conclusions: We demonstrated that the attenuated smallpox vaccine KVAC103 is an available platform for a multivalent vaccine and co-immunization of immunoadjuvants can improve vaccine performance.

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DNA sequence of the gene encoding a major secreted protein of vaccinia virus, strain Lister

Journal of General Virology ◽

10.1099/0022-1317-71-9-2013 ◽

1990 ◽

Vol 71 (9) ◽

pp. 2013-2021 ◽

Cited By ~ 36

Author(s):

A. H. Patel ◽

D. F. Gaffney ◽

J. H. Subak-Sharpe ◽

N. D. Stow

Keyword(s):

Vaccinia Virus ◽

Dna Sequence ◽

Virus Strain ◽

Secreted Protein ◽

Gene Encoding ◽

Vaccinia Virus Strain

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Faculty Opinions recommendation of Characterisation of the gene encoding a protective antigen from Babesia microti identified it as eta subunit of chaperonin containing T-complex protein 1.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1002445.27154 ◽

2001 ◽

Author(s):

David Persing

Keyword(s):

Protective Antigen ◽

Babesia Microti ◽

Gene Encoding ◽

T Complex ◽

Complex Protein

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Differentiation of endemic areas by incidence rates of tick-borne infectious diseases as the basis for choosing prevention strategy and tactics

ЗДОРОВЬЕ НАСЕЛЕНИЯ И СРЕДА ОБИТАНИЯ - ЗНиСО / PUBLIC HEALTH AND LIFE ENVIRONMENT ◽

10.35627/2219-5238/2019-321-12-56-61 ◽

2019 ◽

pp. 56-61

Author(s):

N.V. Rudakov ◽

N.A. Penyevskaya ◽

D.A. Saveliev ◽

S.A. Rudakova ◽

C.V. Shtrek ◽

...

Keyword(s):

High Risk ◽

Infectious Diseases ◽

Population Based ◽

Preventive Therapy ◽

Incidence Rates ◽

Prevention Strategy ◽

Individual Risk ◽

The Individual ◽

Integral Assessment ◽

Very High

Research objective. Differentiation of natural focal areas of Western Siberia by integral incidence rates of tick-borne infectious diseases for determination of the strategy and tactics of their comprehensive prevention. Materials and methods. A retrospective analysis of official statistics for the period 2002-2018 for eight sub-federal units in the context of administrative territories was carried out. The criteria of differentiation were determined by means of three evaluation scales, including long-term mean rates of tick-borne encephalitis, tick-borne borreliosis, and Siberian tick-borne typhus. As a scale gradation tool, we used the number of sample elements between the confidence boundaries of the median. The integral assessment was carried out by the sum of points corresponding to the incidence rates for each of the analyzed infections. Results. The areas of low, medium, above average, high and very high risk of tick-borne infectious diseases were determined. Recommendations on the choice of prevention strategy and tactics were given. In areas of very high and high incidence rates, a combination of population-based and individual prevention strategies is preferable while in other areas a combination of high-risk and individual strategies is recommended. Discussion. Epidemiologic zoning should be the basis of a risk-based approach to determining optimal volumes and directions of preventive measures against natural focal infections. It is necessary to improve the means and methods of determining the individual risk of getting infected and developing tick-borne infectious diseases in case of bites, in view of mixed infection of vectors, as well as methods of post-exposure disease prevention (preventive therapy).

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Neuroblastoma: An Updated Review on Biology and Treatment

Current Drug Metabolism ◽

10.2174/1389200221666191226102231 ◽

2020 ◽

Vol 20 (13) ◽

pp. 1014-1022 ◽

Cited By ~ 2

Author(s):

Suresh Mallepalli ◽

Manoj Kumar Gupta ◽

Ramakrishna Vadde

Keyword(s):

Survival Rate ◽

High Risk ◽

Molecular Mechanisms ◽

Definitive Treatment ◽

Therapeutic Drug ◽

Mycn Amplification ◽

Dependent Manner ◽

High Risk Patients ◽

Treatment And Prevention ◽

Risk Patients

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.

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A mutation in the gene encoding the vaccinia virus 37,000-M(r) protein confers resistance to an inhibitor of virus envelopment and release.

Journal of Virology ◽

10.1128/jvi.65.7.3435-3442.1991 ◽

1991 ◽

Vol 65 (7) ◽

pp. 3435-3442 ◽

Cited By ~ 30

Author(s):

C Schmutz ◽

L G Payne ◽

J Gubser ◽

R Wittek

Keyword(s):

Vaccinia Virus ◽

Gene Encoding

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Signaling through Adenylyl Cyclase Is Essential for Hyphal Growth and Virulence in the Pathogenic FungusCandida albicans

Molecular Biology of the Cell ◽

10.1091/mbc.12.11.3631 ◽

2001 ◽

Vol 12 (11) ◽

pp. 3631-3643 ◽

Cited By ~ 274

Author(s):

Cintia R. C. Rocha ◽

Klaus Schröppel ◽

Doreen Harcus ◽

Anne Marcil ◽

Daniel Dignard ◽

...

Keyword(s):

Mouse Model ◽

Adenylyl Cyclase ◽

Sequence Similarity ◽

Hyphal Growth ◽

Antifungal Drugs ◽

Growth Defect ◽

Adenylyl Cyclases ◽

Gene Encoding ◽

Mutant Cells

The human fungal pathogen Candida albicans switches from a budding yeast form to a polarized hyphal form in response to various external signals. This morphogenetic switching has been implicated in the development of pathogenicity. We have cloned theCaCDC35 gene encoding C. albicansadenylyl cyclase by functional complementation of the conditional growth defect of Saccharomyces cerevisiae cells with mutations in Ras1p and Ras2p. It has previously been shown that these Ras homologues regulate adenylyl cyclase in yeast. The C. albicans adenylyl cyclase is highly homologous to other fungal adenylyl cyclases but has less sequence similarity with the mammalian enzymes. C. albicans cells deleted for both alleles ofCaCDC35 had no detectable cAMP levels, suggesting that this gene encodes the only adenylyl cyclase in C. albicans. The homozygous mutant cells were viable but grew more slowly than wild-type cells and were unable to switch from the yeast to the hyphal form under all environmental conditions that we analyzed in vitro. Moreover, this morphogenetic switch was completely blocked in mutant cells undergoing phagocytosis by macrophages. However, morphogenetic switching was restored by exogenous cAMP. On the basis of epistasis experiments, we propose that CaCdc35p acts downstream of the Ras homologue CaRas1p. These epistasis experiments also suggest that the putative transcription factor Efg1p and components of the hyphal-inducing MAP kinase pathway depend on the function of CaCdc35p in their ability to induce morphogenetic switching. Homozygouscacdc35Δ cells were unable to establish vaginal infection in a mucosal membrane mouse model and were avirulent in a mouse model for systemic infections. These findings suggest that fungal adenylyl cyclases and other regulators of the cAMP signaling pathway may be useful targets for antifungal drugs.

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