Formulation and Immunogenicity of a Potential Multivalent Type III Secretion System-Based Protein Vaccine

Markham, Aaron P.; Barrett, Brooke S.; Esfandiary, Reza; Picking, Wendy L.; Picking, William D.; Joshi, Sangeeta B.; Middaugh, C. Russell

doi:10.1002/jps.22195

Cited by 16 publications

(7 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CT584 does not induce antibody responses in humans infected with C. trachomatis (Wang et al, 2010a). It will be interesting to see the efficacy of a multivalent vaccine based on tip proteins IpaD, BipD, SipD, LcrV, and PcrV, which is in the initial stages of development (Markham et al, 2010). For filamentous-tip protein family, anti-EspA antibodies inhibit cytoskeletal changes in host cells in vitro (La Ragione et al, 2006).…”

Section: Immunization and Therapeutics Targeting T3ssmentioning

confidence: 99%

Multi-Functional Characteristics of the Pseudomonas aeruginosa Type III Needle-Tip Protein, PcrV; Comparison to Orthologs in other Gram-negative Bacteria

Satō¹,

Frank²

2011

Front. Microbio.

View full text Add to dashboard Cite

Pseudomonas aeruginosa possesses a type III secretion system (T3SS) to intoxicate host cells and evade innate immunity. This virulence-related machinery consists of a molecular syringe and needle assembled on the bacterial surface, which allows delivery of T3 effector proteins into infected cells. To accomplish a one-step effector translocation, a tip protein is required at the top end of the T3 needle structure. Strains lacking expression of the functional tip protein fail to intoxicate host cells. P. aeruginosa encodes a T3S that is highly homologous to the proteins encoded by Yersinia spp. The needle-tip proteins of Yersinia, LcrV, and P. aeruginosa, PcrV, share 37% identity and 65% similarity. Other known tip proteins are AcrV (Aeromonas), IpaD (Shigella), SipD (Salmonella), BipD (Burkholderia), EspA (EPEC, EHEC), Bsp22 (Bordetella), with additional proteins identified from various Gram-negative species, such as Vibrio and Bordetella. The tip proteins can serve as a protective antigen or may be critical for sensing host cells and evading innate immune responses. Recognition of the host microenvironment transcriptionally activates synthesis of T3SS components. The machinery appears to be mechanically controlled by the assemblage of specific junctions within the apparatus. These junctions include the tip and base of the T3 apparatus, the needle proteins and components within the bacterial cytoplasm. The tip proteins likely have chaperone functions for translocon proteins, allowing the proper assembly of translocation channels in the host membrane and completing vectorial delivery of effector proteins into the host cytoplasm. Multi-functional features of the needle-tip proteins appear to be intricately controlled. In this review, we highlight the functional aspects and complex controls of T3 needle-tip proteins with particular emphasis on PcrV and LcrV.

show abstract

Section: Immunization and Therapeutics Targeting T3ssmentioning

confidence: 99%

Multi-Functional Characteristics of the Pseudomonas aeruginosa Type III Needle-Tip Protein, PcrV; Comparison to Orthologs in other Gram-negative Bacteria

Satō¹,

Frank²

2011

Front. Microbio.

View full text Add to dashboard Cite

show abstract

“…The presence and proper tip localization of IpaB, IpaC, and IpaD are required for invasion of epithelial cells. Several studies have reported the presence of antibodies against Ipa proteins in serum from infected individuals (5), in subjects immunized with live attenuated organisms during clinical trials (44,45), and following vaccination in animal models (30,49). The conserved nature of IpaB and IpaD among the shigellae and their critical role in pathogenesis make them ideal targets for vaccine development.…”

mentioning

confidence: 99%

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

et al. 2012

Self Cite

View full text Add to dashboard Cite

Shigella spp. are food-and waterborne pathogens that cause severe diarrheal and dysenteric disease associated with high morbidity and mortality. Individuals most often affected are children under 5 years of age in the developing world. The existence of multiple Shigella serotypes and the heterogenic distribution of pathogenic strains, as well as emerging antibiotic resistance, require the development of a broadly protective vaccine. All Shigella spp. utilize a type III secretion system (TTSS) to initiate infection. The type III secretion apparatus (TTSA) is the molecular needle and syringe that form the energized conduit between the bacterial cytoplasm and the host cell to transport effector proteins that manipulate cellular processes to benefit the pathogen. IpaB and IpaD form a tip complex atop the TTSA needle and are required for pathogenesis. Because they are common to all virulent Shigella spp., they are ideal candidate antigens for a subunit-based, broad-spectrum vaccine. We examined the immunogenicity and protective efficacy of IpaB and IpaD, alone or combined, coadministered with a double mutant heat-labile toxin (dmLT) from Escherichia coli, used as a mucosal adjuvant, in a mouse model of intranasal immunization and pulmonary challenge. Robust systemic and mucosal antibody-and T cell-mediated immunities were induced against both proteins, particularly IpaB. Mice immunized in the presence of dmLT with IpaB alone or IpaB combined with IpaD were fully protected against lethal pulmonary infection with Shigella flexneri and Shigella sonnei. We provide the first demonstration that the Shigella TTSAs IpaB and IpaD are promising antigens for the development of a cross-protective Shigella vaccine.

show abstract

“…More examples examining the chemical and physical characterization of proteinbased vaccines can be found from other previously published work, including studies of a 2-fl uorohistidine-labeled analogue of recombinant anthrax protective antigen , Clostridium diffi cile toxins and toxoids (Salnikova et al 2008a , b ), gram-negative bacterial type III secretion system-based protein vaccines Markham et al 2010 ), an aluminum salt-adjuvanted trivalent recombinant protein-based vaccine candidate against Streptococcus pneumonia , and a recombinant pneumolysin protein antigen as a pneumococcal vaccine candidate ).…”

Section: Protein-based Vaccinesmentioning

confidence: 99%

Subunit Vaccine Delivery

Foged¹,

Rades²,

Perrie³

et al. 2015

Advances in Delivery Science and Technology

View full text Add to dashboard Cite

Formulation and Immunogenicity of a Potential Multivalent Type III Secretion System-Based Protein Vaccine

Cited by 16 publications

References 52 publications

Multi-Functional Characteristics of the Pseudomonas aeruginosa Type III Needle-Tip Protein, PcrV; Comparison to Orthologs in other Gram-negative Bacteria

Multi-Functional Characteristics of the Pseudomonas aeruginosa Type III Needle-Tip Protein, PcrV; Comparison to Orthologs in other Gram-negative Bacteria

Broadly Protective Shigella Vaccine Based on Type III Secretion Apparatus Proteins

Subunit Vaccine Delivery

Contact Info

Product

Resources

About