Novel Catanionic Surfactant Vesicle Vaccines Protect against Francisella tularensis LVS and Confer Significant Partial Protection against F. tularensis Schu S4 Strain

Richard, Katharina; Mann, Barbara J.; Stocker, Lenea; Barry, Eileen M.; Qin, Aiping; Cole, Leah E.; Hurley, Matthew T.; Ernst, Robert K.; Michalek, Suzanne M.; Stein, Daniel C.; DeShong, Philip; Vogel, Stefanie N.

doi:10.1128/cvi.00738-13

Cited by 24 publications

(35 citation statements)

References 77 publications

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“…We previously showed that F. tularensis antigens detected by LVS-V-or Schu S4-V immune sera in Western blot analyses are highly conserved across the major evolutionary clades of F. tularensis strains (25). We next asked whether the addition of MPL adjuvant enhanced the detection of either the same or additional F. tularensis antigens.…”

Section: Immunization Of Mice With Lvs-v Elicits Serummentioning

confidence: 99%

“…While immunization with LVS-V protected fully and was associated with high serum titers of IgG, significant partial protection was gained through immune stimulation with the empty V, despite an absence of IgG and cytokine production. This suggested that the V possess intrinsic innate immune stimulatory activity (25). To determine the efficacy of LVS-V nanoparticles to protect against respiratory tularemia, which has a more severe clinical presentation, we tested this vaccine in an i.n.…”

Section: Immunization Of Mice With Lvs-v Elicits Serummentioning

confidence: 99%

“…with ϳ5,000 CFU of F. tularensis LVS. Clinical symptoms and survival were monitored for 2 weeks after the live challenge, as described previously (25). While the majority of naive control mice succumbed to tularemia within 6 to 8 days following challenge, all LVS-V-immunized mice (with or without MPL) survived challenge with minimal weight loss and only mild clinical symptoms (score of 1 [see Materials and Methods for a description of the clinical scores]) (Fig.…”

Section: Immunization Of Mice With Lvs-v Elicits Serummentioning

confidence: 99%

“…), resulted in a significant delay in time to death compared to that of unimmunized mice, with ϳ25% survivors in mice challenged i.n. with F. tularensis (25). Anti-LVS-V and anti-Schu S4-V antisera cross-reacted with the other strain in Western blot analysis, as well as with clinical isolates spanning all major clades of F. tularensis (25).…”

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confidence: 99%

“…These can be "functionalized" by incorporation of lipid-conjugated molecules (23,24) or bacterial lysates (25). Thus, V represent a potentially effective vehicle for vaccine delivery, with significant advantages over those composed of phospholipids or nonionic surfactants, liposomes and niosomes, e.g., low cost, ease of formation, and high stability (22,26).…”

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confidence: 99%

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Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

Richard

Mann

Qin

et al. 2017

Clin Vaccine Immunol

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Francisella tularensis, a bacterial biothreat agent, has no approved vaccine in the United States. Previously, we showed that incorporating lysates from partially attenuated F. tularensis LVS or fully virulent F. tularensis Schu S4 strains into catanionic surfactant vesicle (V) nanoparticles (LVS-V and Schu S4-V, respectively) protected fully against F. tularensis LVS intraperitoneal (i.p.) challenge in mice. However, we achieved only partial protection against F. tularensis Schu S4 intranasal (i.n.) challenge, even when employing heterologous prime-boost immunization strategies. We now extend these findings to show that both LVS-V and Schu S4-V immunization (i.p./i.p.) elicited similarly high titers of anti-F. tularensis IgG and that the titers could be further increased by adding monophosphoryl lipid A (MPL), a nontoxic Toll-like receptor 4 (TLR4) adjuvant that is included in several U.S. FDA-approved vaccines. LVS-VϩMPL immune sera also detected more F. tularensis antigens than LVS-V immune sera and, after passive transfer to naive mice, significantly delayed the time to death against F. tularensis Schu S4 subcutaneous (s.c.) but not i.n. challenge. Active immunization with LVS-VϩMPL (i.p./i.p.) also increased the frequency of gamma interferon (IFN-␥)-secreting activated helper T cells, IFN-␥ production, and the ability of splenocytes to control intramacrophage F. tularensis LVS replication ex vivo. Active LVS-VϩMPL immunization via heterologous routes (i.p./i.n.) significantly elevated IgA and IgG levels in bronchoalveolar lavage fluid and significantly enhanced protection against i.n. F. tularensis Schu S4 challenge (to ϳ60%). These data represent a significant step in the development of a subunit vaccine against the highly virulent type A strains.KEYWORDS Francisella tularensis, LVS, Schu S4, catanionic surfactant, immunization, mice, monophosphoryl lipid A, nanoparticle, subunit vaccine, tularemia F rancisella tularensis, the causative agent of tularemia, is a Gram-negative coccobacillus. The infectious dose for F. tularensis can be extremely small (Ͻ10 organisms), depending on the strain and route of infection (1-3). Type A strains, such as F. tularensis Schu S4, are associated with high mortality and morbidity in mammals (1-3). F. tularensis is an excellent model organism for immune-evasive pathogens because of its broad host range, including rodents, and because of its rapid progression through the stages of infection. Clinical presentation of tularemia depends on the route of infection,

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Section: Immunization Of Mice With Lvs-v Elicits Serummentioning

confidence: 99%

Section: Immunization Of Mice With Lvs-v Elicits Serummentioning

confidence: 99%

Section: Immunization Of Mice With Lvs-v Elicits Serummentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

Richard

Mann

Qin

et al. 2017

Clin Vaccine Immunol

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Catanionic Surfactant Vesicles as a New Platform for Probing Glycan–Protein Interactions

Mahle

Dashaputre

DeShong

et al. 2018

Adv Funct Materials

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Glycomics lags substantially behind proteomics and genomics in its ability to decipher and synthesize complex glycans. The slow progress in deciphering glycan interactions at a molecular level is in large part due to the absence of a functional system to express, on a large scale, carbohydrates of known structure, in the context of a biologically relevant assay system. Here we describe the characterization of a glycan-functionalized catanionic surfactant vesicles (CVs) as a platform for glycan synthesis, and to demonstrate that the resulting glycan-functionalized CVs can serve as a scaffold for the interrogation of protein-glycan interactions. We demonstrate that N. gonorrhoeae lipooligosaccharide (LOS) glycosyltransferase LgtE, an enzyme that catalyzes the addition of galactose onto a terminal glucose found on LOS can be used to biochemically modify LOS or glucose functionalized CVs. CVs were characterized by differential lectin binding using flow cytometry. LgtE activity was measured on whole cells and LOS functionalized vesicles and found to have approximately the same biochemical properties. We further demonstrate that CVs can be ink-jet printed. This paper presents proof-of-concept that glycan-functionalized catanionic vesicles can be used to create a high-specificity and high-throughput glycan array that will allow for the investigation of a variety of protein-glycan interactions.

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Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

Fan

Moon

2016

WIREs Nanomed Nanobiotechnol

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Bioterrorism agents that can be easily transmitted with high mortality rates and cause debilitating diseases pose major threats to national security and public health. The recent Ebola virus outbreak in West Africa and ongoing Zika virus outbreak in Brazil, now spreading throughout Latin America, are case examples of emerging infectious pathogens that have incited widespread fear and economic and social disruption on a global scale. Prophylactic vaccines would provide effective countermeasures against infectious pathogens and biological warfare agents. However, traditional approaches relying on attenuated or inactivated vaccines have been hampered by their unacceptable levels of reactogenicity and safety issues, whereas subunit antigen-based vaccines suffer from suboptimal immunogenicity and efficacy. In contrast, particulate vaccine delivery systems offer key advantages, including efficient and stable delivery of subunit antigens, co-delivery of adjuvant molecules to bolster immune responses, low reactogenicity due to the use of biocompatible biomaterials, and robust efficiency to elicit humoral and cellular immunity in systemic and mucosal tissues. Thus, vaccine nanoparticles and microparticles are promising platforms for clinical development of biodefense vaccines. In this review, we summarize the current status of research efforts to develop particulate vaccine delivery systems against bioterrorism agents and emerging infectious pathogens.

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Novel Catanionic Surfactant Vesicle Vaccines Protect against Francisella tularensis LVS and Confer Significant Partial Protection against F. tularensis Schu S4 Strain

Cited by 24 publications

References 77 publications

Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

Monophosphoryl Lipid A Enhances Efficacy of a Francisella tularensis LVS-Catanionic Nanoparticle Subunit Vaccine against F. tularensis Schu S4 Challenge by Augmenting both Humoral and Cellular Immunity

Catanionic Surfactant Vesicles as a New Platform for Probing Glycan–Protein Interactions

Particulate delivery systems for vaccination against bioterrorism agents and emerging infectious pathogens

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