Babesia microti Protein BmSP44 Is a Novel Protective Antigen in a Mouse Model of Babesiosis

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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Corrigendum: The Tick Microbiota Dysbiosis Promote Tick-Borne Pathogen Transstadial Transmission in a Babesia microti Infected Mouse Model

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.765387 ◽

2021 ◽

Vol 11 ◽

Author(s):

Nana Wei ◽

Jie Cao ◽

Houshuang Zhang ◽

Yongzhi Zhou ◽

Jinlin Zhou

Keyword(s):

Mouse Model ◽

Infected Mouse ◽

Babesia Microti ◽

Transstadial Transmission

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

BMC Microbiology ◽

10.1186/s12866-021-02121-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Deok Bum Park ◽

Bo-Eun Ahn ◽

Hosun 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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BA3338, a surface layer homology domain possessing protein augments immune response and protection efficacy of protective antigen against Bacillus anthracis in mouse model

Journal of Applied Microbiology ◽

10.1111/jam.14624 ◽

2020 ◽

Vol 129 (2) ◽

pp. 443-452 ◽

Cited By ~ 1

Author(s):

M. Kumar ◽

N. Puranik ◽

A. Varshney ◽

N. Tripathi ◽

V. Pal ◽

...

Keyword(s):

Immune Response ◽

Surface Layer ◽

Mouse Model ◽

Bacillus Anthracis ◽

Protective Antigen ◽

Protection Efficacy

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Using a Syrian (Golden) Hamster Biological Model for the Evaluation of Recombinant Anthrax Vaccines

Life ◽

10.3390/life11121388 ◽

2021 ◽

Vol 11 (12) ◽

pp. 1388

Author(s):

Tatiana Kravchenko ◽

Galina Titareva ◽

Irina Bakhteeva ◽

Tatiana Kombarova ◽

Alexander Borzilov ◽

...

Keyword(s):

Mouse Model ◽

Recombinant Proteins ◽

Protective Antigen ◽

Lethal Factor ◽

Biological Model ◽

Specific Antibodies ◽

Syrian Hamsters ◽

Factor I ◽

Anthrax Vaccines ◽

Pa Domain

In this paper, we demonstrate that a Syrian hamster biological model can be applied to the study of recombinant anthrax vaccines. We show that double vaccination with recombinant proteins, such as protective antigen (PA) and fusion protein LF1PA4, consisting of lethal factor I domain (LF) and PA domain IV, leads to the production of high titers of specific antibodies and to protection from infection with the toxicogenic encapsulated attenuated strain B. anthracis 71/12. In terms of antibody production and protection, Syrian hamsters were much more comparable to guinea pigs than mice. We believe that Syrian hamsters are still underestimated as a biological model for anthrax research, and, in some cases, they can be used as a replacement or at least as a complement to the traditionally used mouse model.

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Conformational Nature of the Borrelia burgdorferiDecorin Binding Protein A Epitopes That Elicit Protective Antibodies

Infection and Immunity ◽

10.1128/iai.69.8.4799-4807.2001 ◽

2001 ◽

Vol 69 (8) ◽

pp. 4799-4807 ◽

Cited By ~ 16

Author(s):

Nancy D. Ulbrandt ◽

David R. Cassatt ◽

Nita K. Patel ◽

William C. Roberts ◽

Christine M. Bachy ◽

...

Keyword(s):

Immune Response ◽

Mouse Model ◽

Protective Antigen ◽

Binding Protein ◽

Protein A ◽

Protective Immune Response ◽

Protective Antibodies ◽

Functional Antibodies ◽

The Stability ◽

Carboxy Terminal

ABSTRACT Decorin binding protein A (DbpA) has been shown by several laboratories to be a protective antigen for the prevention of experimental Borrelia burgdorferi infection in the mouse model of Lyme borreliosis. However, different recombinant forms of the antigen having either lipidated amino termini, approximating the natural secretion and posttranslational processing, or nonprocessed cytosolic forms have elicited disparate levels of protection in the mouse model. We have now used the unique functional properties of this molecule to investigate the structural requirements needed to elicit a protective immune response. Genetic and physicochemical alterations to DbpA showed that the ability to bind to the ligand decorin is indicative of a potent immunogen but is not conclusive. By mutating the two carboxy-terminal nonconserved cysteines of DbpA from B. burgdorferi strain N40, we have determined that the stability afforded by the putative disulfide bond is essential for the generation of protective antibodies. This mutated protein was more sensitive to thermal denaturation and proteolysis, suggesting that it is in a less ordered state. Immunization with DbpA that was thermally denatured and functionally inactivated stimulated an immune response that was not protective and lacked bactericidal antibodies. Antibodies against conformationally altered forms of DbpA also failed to kill heterologous B. garinii and B. afzelii strains. Additionally, nonsecreted recombinant forms of DbpAN40were found to be inferior to secreted lipoprotein DbpAN40 in terms of functional activity and antigenic potency. These data suggest that elicitation of a bactericidal and protective immune response to DbpA requires a properly folded conformation for the production of functional antibodies.

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