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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

Immunization Schedules I and II.(A) C57BL/6 mice were immunized intranasally (i.n.) either with TMV-monoconjugate (60 μg/mouse) or TMV-multiconjugate vaccine formulations (20 μg each of OmpA-TMV; DnaK-TMV and Tul4-TMV conjugates. Total 60 μg/mouse) and booster vaccinations were administered i.n. using dosages similar to those for primary immunization on days 7 and 14 of the post-primary immunization (Schedule I). (B) Alternatively, mice were administered TMV-multiconjugate vaccines with booster immunizations i.n. on day 5 and 14 and subcutaneously (s.c.) on days 7 and 14 post-primary immunization (Schedule II). The dosages used were similar to those described for TMV-multiconjugate vaccine in A. Mice inoculated with TMV (30 μg/mouse) in a manner similar to the vaccinated groups were kept as controls.
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pone.0130858.g002: Immunization Schedules I and II.(A) C57BL/6 mice were immunized intranasally (i.n.) either with TMV-monoconjugate (60 μg/mouse) or TMV-multiconjugate vaccine formulations (20 μg each of OmpA-TMV; DnaK-TMV and Tul4-TMV conjugates. Total 60 μg/mouse) and booster vaccinations were administered i.n. using dosages similar to those for primary immunization on days 7 and 14 of the post-primary immunization (Schedule I). (B) Alternatively, mice were administered TMV-multiconjugate vaccines with booster immunizations i.n. on day 5 and 14 and subcutaneously (s.c.) on days 7 and 14 post-primary immunization (Schedule II). The dosages used were similar to those described for TMV-multiconjugate vaccine in A. Mice inoculated with TMV (30 μg/mouse) in a manner similar to the vaccinated groups were kept as controls.

Mentions: Two different immunization schedules were used. In the first immunization schedule (Schedule I) C57BL/6 mice were immunized intranasally (i.n.) with 60μg of TMV monoconjugate or TMV-multiconjugate vaccine. Mice were immunized i.n. with 30μl (15μl/ nostril) volume of each of the vaccine formulation or the TMV controls. Booster vaccinations using dosages similar to the primary immunization were administered on days 7 and 14 after the primary immunization. Mice receiving 30μg of TMV alone and administered in a fashion similar to the vaccine groups were kept as controls (Fig 2A). Mice were monitored for any adverse reaction following each vaccine administration.


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)

Immunization Schedules I and II.(A) C57BL/6 mice were immunized intranasally (i.n.) either with TMV-monoconjugate (60 μg/mouse) or TMV-multiconjugate vaccine formulations (20 μg each of OmpA-TMV; DnaK-TMV and Tul4-TMV conjugates. Total 60 μg/mouse) and booster vaccinations were administered i.n. using dosages similar to those for primary immunization on days 7 and 14 of the post-primary immunization (Schedule I). (B) Alternatively, mice were administered TMV-multiconjugate vaccines with booster immunizations i.n. on day 5 and 14 and subcutaneously (s.c.) on days 7 and 14 post-primary immunization (Schedule II). The dosages used were similar to those described for TMV-multiconjugate vaccine in A. Mice inoculated with TMV (30 μg/mouse) in a manner similar to the vaccinated groups were kept as controls.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0130858.g002: Immunization Schedules I and II.(A) C57BL/6 mice were immunized intranasally (i.n.) either with TMV-monoconjugate (60 μg/mouse) or TMV-multiconjugate vaccine formulations (20 μg each of OmpA-TMV; DnaK-TMV and Tul4-TMV conjugates. Total 60 μg/mouse) and booster vaccinations were administered i.n. using dosages similar to those for primary immunization on days 7 and 14 of the post-primary immunization (Schedule I). (B) Alternatively, mice were administered TMV-multiconjugate vaccines with booster immunizations i.n. on day 5 and 14 and subcutaneously (s.c.) on days 7 and 14 post-primary immunization (Schedule II). The dosages used were similar to those described for TMV-multiconjugate vaccine in A. Mice inoculated with TMV (30 μg/mouse) in a manner similar to the vaccinated groups were kept as controls.
Mentions: Two different immunization schedules were used. In the first immunization schedule (Schedule I) C57BL/6 mice were immunized intranasally (i.n.) with 60μg of TMV monoconjugate or TMV-multiconjugate vaccine. Mice were immunized i.n. with 30μl (15μl/ nostril) volume of each of the vaccine formulation or the TMV controls. Booster vaccinations using dosages similar to the primary immunization were administered on days 7 and 14 after the primary immunization. Mice receiving 30μg of TMV alone and administered in a fashion similar to the vaccine groups were kept as controls (Fig 2A). Mice were monitored for any adverse reaction following each vaccine administration.

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