Yersinia pestis Vaccines

Creative Biolabs is a world leader in the field of bacterial vaccine development. With our extensive experience and advanced platform, we are therefore confident in offering the best services for vaccine development against disease caused by Yersinia pestis and guarantee the finest results for our customers all over the world.

Plague can be a life-threatening disease including three main forms, pneumonic, septicemic, and bubonic plagues, caused by Yersinia pestis (Y. pestis) which is a Gram-negative facultative anaerobic bacterium in the family of Enterobacteriaceae. Its characteristic features include non-motile, stick-shaped and negative for urease, lactose fermentation, and indole. It is one of several bacterial pathogens considered to be a potential agent of bioterrorism. Y. pestis mainly infects rats and other rodents and fleas are the prime vectors carrying the bacteria from one species to another. The bacterium infects to human can occur from eating infected animals such as squirrels and they can transmit it to another person via aerosol droplets.

Fig.2 Y. pestis surface components
targeted for vaccine design.

Subunit Plague Vaccines

The two well-characterized Y. pestis antigens, capsular subunit protein F1 and the low-calcium response V antigen (LcrV) were proven to be a safe and effective plague vaccine in eliciting protection against plague in different animal models. The recombinant F1 antigen is extracted from the plague bacterium and the recombinant V antigen is a fusion of LcrV of Y. pseudotuberculosis with the IgG-binding domain of staphylococcal protein A. These two antigens were combined together to provide stronger protection than that elicited with each antigen alone. Moreover, analysis of sera for the IgG subclasses revealed the prevalence of IgG1 over IgG2a directed against both F1 and LcrV. F1 is the structural unit of the capsular layer. V forms a pore at the tip of the injectisome needle and facilitates translocation of Yersinia outer proteins (Yops) into the host cell. F1 and V are two principal targets for the plague subunit vaccines.

Plague DNA Vaccines

Recently, it was proved that Y. pestis antigens were expressed with the signal sequence of human tissue plasminogen activator that can improve the secretion of soluble proteins. Therefore, this well-developed system for DNA vaccination with LcrV allowed elicitation of a significant antibody response and provided protection against intranasal challenge with Y. pestis. In addition, this system can improve LcrV DNA vaccine by enhancing its performance with the help of the F1-YscF construct. This perspective technology must be optimized to allow its use in vaccination against plague.

Virally Vectored Live Plague Vaccines

There is a replication-deficient adenovirus (Ad) gene-transfer vector encoding V antigen and it is demonstrated that a single injection of the recombinant virus elicits strong anti-LcrV serum antibody responses, LcrV-specific CD4⁺ and CD8⁺ responses, and protective immunity against an intranasal Y. pestis challenge. Fusion of F1 or LcrV to the adenovirus capsid protein can elicit strong humoral immunity in mice immunized intramuscularly, with greater efficacy than the injection of adjuvanted purified V or F1.

Live Bacterially Vectored Plague Vaccines

Another bacterium is the commensal, non-pathogenic Lactococcus lactis that has been used to deliver LcrV with some success. Using live attenuated Salmonella to deliver Y. pestis antigens has received considerable attention as vectors for the delivery of a variety of heterologous vaccine antigens. After delivery by the oral route, the bacteria enter the intestinal sub-epithelium via M-cells and are trafficked through mesenteric lymph nodes to fixed macrophages in the spleen and liver. This colonization pathway results in the induction of mucosal and systemic immune responses.

Combination Vaccine

There is a combination vaccine which simultaneously protects animals against the challenges with Y. pestis and the lethal toxin of B. anthracis, demonstrating that a single biodefense vaccine can protect against a bioterror attack with weaponized B. anthracis and/or Y. pestis. This bivalent anthrax-plague vaccine is a strong candidate for stockpiling as part of national preparedness against two of the deadliest bioterror threats.

Creative Biolabs is a highly proactive, robust and diversified company with a strong, scientifically-proven background of bacterial vaccine development. We have experts who are able to help you with the vaccine development against brucellosis caused by Y. pestis. If you are interested in our services, please contact us for more details.

Reference

1. Pan Tao. (2017). “A bivalent Anthrax-Plague vaccine that can protect against two tier-1 bioterror pathogens, Bacillus anthracis and Yersinia pestis.” Front. Immuno. 8, 1-10.

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