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Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV) Based Delivery System.

Banik S, Mansour AA, Suresh RV, Wykoff-Clary S, Malik M, McCormick AA, Bakshi CS - PLoS ONE (2015)

Bottom Line: Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens.This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis.Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America.

ABSTRACT
Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA), chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100) doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

No MeSH data available.


Related in: MedlinePlus

Vaccine Formulations.Two different vaccine formulations were used. In the first vaccine formulation all three recombinant proteins OmpA, DnaK and Tul4 were conjugated to a single TMV virion (TMV-monoconjugate vaccine). The second vaccine formulation contained each recombinant protein of F. tularensis conjugated individually to TMV and then mixed in equal concentrations to generate a TMV-multiconjugate vaccine.
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pone.0130858.g001: Vaccine Formulations.Two different vaccine formulations were used. In the first vaccine formulation all three recombinant proteins OmpA, DnaK and Tul4 were conjugated to a single TMV virion (TMV-monoconjugate vaccine). The second vaccine formulation contained each recombinant protein of F. tularensis conjugated individually to TMV and then mixed in equal concentrations to generate a TMV-multiconjugate vaccine.

Mentions: Two different vaccine formulations were used. In the first formulation, all three recombinant proteins OmpA, DnaK and Tul4 were conjugated to a single TMV virion. This vaccine formulation was designated as TMV-monoconjugate vaccine. Mice were immunized with 60μg of TMV monoconjugate vaccine (~30μg TMV and 30μg of recombinant proteins). In the second vaccine formulation, each individual protein was conjugated to the TMV individually (10μg TMV + 10μg recombinant protein) and then each of the three TMV-protein conjugates were mixed in equal concentrations [20μg x 3 = 60μg (30μg TMV + 30μg recombinant proteins)]. This formulation was designated as TMV-multiconjugate vaccine (Fig 1). Based on the amount of TMV that each of the vaccinated mouse received (30μg), mice inoculated with an 30μg of TMV served as controls.


Development of a Multivalent Subunit Vaccine against Tularemia Using Tobacco Mosaic Virus (TMV) Based Delivery System.

Banik S, Mansour AA, Suresh RV, Wykoff-Clary S, Malik M, McCormick AA, Bakshi CS - PLoS ONE (2015)

Vaccine Formulations.Two different vaccine formulations were used. In the first vaccine formulation all three recombinant proteins OmpA, DnaK and Tul4 were conjugated to a single TMV virion (TMV-monoconjugate vaccine). The second vaccine formulation contained each recombinant protein of F. tularensis conjugated individually to TMV and then mixed in equal concentrations to generate a TMV-multiconjugate vaccine.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476615&req=5

pone.0130858.g001: Vaccine Formulations.Two different vaccine formulations were used. In the first vaccine formulation all three recombinant proteins OmpA, DnaK and Tul4 were conjugated to a single TMV virion (TMV-monoconjugate vaccine). The second vaccine formulation contained each recombinant protein of F. tularensis conjugated individually to TMV and then mixed in equal concentrations to generate a TMV-multiconjugate vaccine.
Mentions: Two different vaccine formulations were used. In the first formulation, all three recombinant proteins OmpA, DnaK and Tul4 were conjugated to a single TMV virion. This vaccine formulation was designated as TMV-monoconjugate vaccine. Mice were immunized with 60μg of TMV monoconjugate vaccine (~30μg TMV and 30μg of recombinant proteins). In the second vaccine formulation, each individual protein was conjugated to the TMV individually (10μg TMV + 10μg recombinant protein) and then each of the three TMV-protein conjugates were mixed in equal concentrations [20μg x 3 = 60μg (30μg TMV + 30μg recombinant proteins)]. This formulation was designated as TMV-multiconjugate vaccine (Fig 1). Based on the amount of TMV that each of the vaccinated mouse received (30μg), mice inoculated with an 30μg of TMV served as controls.

Bottom Line: Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens.This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis.Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, New York, United States of America.

ABSTRACT
Francisella tularensis is a facultative intracellular pathogen, and is the causative agent of a fatal human disease known as tularemia. F. tularensis is classified as a Category A Biothreat agent by the CDC based on its use in bioweapon programs by several countries in the past and its potential to be used as an agent of bioterrorism. No licensed vaccine is currently available for prevention of tularemia. In this study, we used a novel approach for development of a multivalent subunit vaccine against tularemia by using an efficient tobacco mosaic virus (TMV) based delivery platform. The multivalent subunit vaccine was formulated to contain a combination of F. tularensis protective antigens: OmpA-like protein (OmpA), chaperone protein DnaK and lipoprotein Tul4 from the highly virulent F. tularensis SchuS4 strain. Two different vaccine formulations and immunization schedules were used. The immunized mice were challenged with lethal (10xLD100) doses of F. tularensis LVS on day 28 of the primary immunization and observed daily for morbidity and mortality. Results from this study demonstrate that TMV can be used as a carrier for effective delivery of multiple F. tularensis antigens. TMV-conjugate vaccine formulations are safe and multiple doses can be administered without causing any adverse reactions in immunized mice. Immunization with TMV-conjugated F. tularensis proteins induced a strong humoral immune response and protected mice against respiratory challenges with very high doses of F. tularensis LVS. This study provides a proof-of-concept that TMV can serve as a suitable platform for simultaneous delivery of multiple protective antigens of F. tularensis. Refinement of vaccine formulations coupled with TMV-targeting strategies developed in this study will provide a platform for development of an effective tularemia subunit vaccine as well as a vaccination approach that may broadly be applicable to many other bacterial pathogens.

No MeSH data available.


Related in: MedlinePlus