Sizing the optimal dimensions of a vaccine delivery system: a particulate matter

Slütter, Bram; Jiskoot, Wim

doi:10.1517/17425247.2016.1121989

Cited by 45 publications

(38 citation statements)

References 18 publications

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“…It is unlikely that a stand-alone subunit or a combination of two subunits with adjuvant will be protective in humans. While a particle composed of MPL-AH and proteins was used for this study, either a better formulation or a unique particle may be required to maintain the antigen in lymph nodes to elicit memory (23,24). Nevertheless, the most important finding is that the vaccine formulation of S1S2 provided protection not only against the homologous S. Typhimurium but also against the heterologous S. Enteritidis.…”

Section: Discussionmentioning

confidence: 99%

Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes

et al. 2018

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Nontyphoidal serotypes (NTS) are the leading cause of hospitalization and death due to foodborne illnesses. NTS are the costliest of the foodborne pathogens and cause ∼$4 billion annually in health care costs. In Africa, new invasive NTS are the leading cause of bacteremia, especially in HIV-positive children and adults. Current vaccines against are not broadly protective and most are directed at the typhoid-causing serotypes, not the NTS. All strains require two type III secretion systems (T3SS) for virulence. The T3SS needle tip protein and the first translocator are localized to the T3SS needle tip and are required for pathogenesis of Collectively they are 95 to 98% conserved at the amino acid sequence level among all strains. The pathogenicity island 1 or 2 tip and first translocator proteins were genetically fused to produce the S1 and S2 fusion proteins, respectively, as potential vaccine candidates. S1 and S2 were then characterized using spectroscopic techniques to understand their structural and biophysical properties. Formulated at the proper pH, S1, S2, or S1 plus S2 (S1S2), admixed with adjuvant, was used to immunize mice followed by a lethal challenge with serotype Typhimurium or serotype Enteritidis. The S1S2 formulation provided the highest protective efficacy, thus demonstrating that an S1S2 subunit vaccine can provide broad, serotype-independent protection, possibly against all serotypes. Such a finding would be transformative in improving human health.

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Section: Discussionmentioning

confidence: 99%

Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes

et al. 2018

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“…Furthermore, non-proteinaceous subvisible particles with adsorbed protein can sometimes lead to enhanced immunogenicity, although not consistently for all types of particles and all proteins. It is worth noting that since particle size is recognized as a contributor to immune responses to vaccines 82–84 , it is reasonable to assume that size may also be an important attribute to consider in the context of immunogenicity of therapeutic protein aggregates and particles.…”

Section: Conclusion and Recommendationsmentioning

confidence: 99%

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Jiskoot

Kijanka

Randolph

et al. 2016

Journal of Pharmaceutical Sciences

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The success of clinical and commercial therapeutic proteins is rapidly increasing, but their potential immunogenicity is an ongoing concern. Most of the studies that have been conducted over the past few years to examine the importance of various product-related attributes (in particular several types of aggregates and particles) and treatment regimen (such as dose, dosing schedule and route of administration) in the development of unwanted immune responses have utilized one of a variety of mouse models. In this review we discuss the utility and drawbacks of different mouse models that have been used for this purpose. Moreover, we summarize the lessons these models have taught us and some of the challenges they present. Finally, we provide recommendations for future research utilizing mouse models to improve our understanding of critical factors that may contribute to protein immunogenicity.

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“…This suggests that the ideal encapsulating diameter for antibodies is in the micrometer range. Furthermore, it remains to be determined whether similar trends in particle diameters occur in larger animal models or humans and will require tight control over the distribution of particle diameters as well as the use of the most effective diameter characterization techniques 29 . There is also evidence that the surface chemistry of the particle can affect the rate of uptake by human dendritic cells in vitro 72 .…”

Section: Discussionmentioning

confidence: 99%

“…The diameter of nanoscale biodegradable particles is a key dosage form parameter 26–29 that potentially affects the magnitude of CD4 + and CD8 + T cells as well as Th1/Th2 memory subsets of CD4 + T cells generated by co-encapsulated immunostimulant/subunit vaccines after systemic immunization 30, 31 . It remains unclear, however, whether the diameter of co-encapsulating biodegradable particle affects the generation of mucosal and systemic memory T cells by co-encapsulated immunostimulants/subunit vaccines after mucosal immunization.…”

Section: Introductionmentioning

confidence: 99%

Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8⁺ T Cells in a Diameter-Dependent Manner

et al. 2017

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The diameter of biodegradable particles used to co-encapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8+ T cells generated by systemic immunization. Possible effects on the magnitude of CD8+ T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles. We then compared total magnitude, effector/central memory (CD127/KRLG1/CD62L), and IFN-γ/TNF-α/IL-2 secreting subsets of pp89-specific CD8+ T cells as well as protection of naïve female BALB/c mice against primary respiratory infection with MCMV 21 days after respiratory immunization. We found that decreasing the diameter of encapsulating particle from ~5.4 µm to ~350 nm: (i.) increased the magnitude of pp89-specific CD8+ T cells in the lungs and spleen (ii.) partially changed CD127/KLRG1 effector memory subsets in the lungs but not the spleen (iii.) changed CD127/KRLG1/CD62L effector/central memory subsets in the spleen (iv.) changed pp89-responsive IFN-γ/TNF-α/IL-2 secreting subsets in the lungs and spleen (v.) did not affect the extent to which encapsulation increased efficacy against primary MCMV respiratory infection over unencapsulated pp89-RR-EP67. Thus, although not observed under our current experimental conditions with MCMV, varying the diameter of nanoscale biodegradable particles may increase the efficacy of mucosal immunization with co-encapsulated immunostimulant/subunit vaccines against certain pathogens by selectively increasing memory subset(s) of CD8+ T cells that correlate the strongest with protection.

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Sizing the optimal dimensions of a vaccine delivery system: a particulate matter

Cited by 45 publications

References 18 publications

Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes

Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8⁺ T Cells in a Diameter-Dependent Manner

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Sizing the optimal dimensions of a vaccine delivery system: a particulate matter

Cited by 45 publications

References 18 publications

Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes

Characterization and Protective Efficacy of Type III Secretion Proteins as a Broadly Protective Subunit Vaccine against Salmonella enterica Serotypes

Mouse Models for Assessing Protein Immunogenicity: Lessons and Challenges

Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8+ T Cells in a Diameter-Dependent Manner

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Resources

About

Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8⁺ T Cells in a Diameter-Dependent Manner