Molecular Adjuvants Based on Nonpyrogenic Lipophilic Derivatives of norAbuMDP/GMDP Formulated in Nanoliposomes: Stimulation of Innate and Adaptive Immunity

Knotigová, Pavlína Turánek; Zyka, Daniel; Mašek, Josef; Ковальова, А. М.; Křupka, Michal; Bartheldyová, Eliška; Kulich, Pavel; Koudelka, Štěpán; Lukac, R; Kauerová, Zuzana; Vácek, A; Horynová, Milada; Kozubı́k, Alois; Miller, Andrew D.; Fekete, Ladislav; Kratochvílová, Irena; Ježek, Jan; Ledvina, M; Raška, Milan; Tuřánek, Jaroslav

doi:10.1007/s11095-014-1516-y

Cited by 19 publications

(18 citation statements)

References 42 publications

(46 reference statements)

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“…coli , a non-lipidated version of OspC was constructed by eliminating the signal sequence (amino acid residues 1–18) and a high yield of expression was achieved [ 13 – 15 ]. Nevertheless, non-lipidated OspC is only a weak immunogen, stressing the need for strong adjuvant co-administration [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

et al. 2016

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Lyme disease, Borrelia burgdorferi-caused infection, if not recognized and appropriately treated by antibiotics, may lead to chronic complications, thus stressing the need for protective vaccine development. The immune protection is mediated by phagocytic cells and by Borrelia-specific complement-activating antibodies, associated with the Th1 immune response. Surface antigen OspC is involved in Borrelia spreading through the host body. Previously we reported that recombinant histidine tagged (His-tag) OspC (rOspC) could be attached onto liposome surfaces by metallochelation. Here we report that levels of OspC-specific antibodies vary substantially depending upon whether rOspC possesses an N' or C' terminal His-tag. This is the case in mice immunized: (a) with rOspC proteoliposomes containing adjuvants MPLA or non-pyrogenic MDP analogue MT06; (b) with free rOspC and Montanide PET GEL A; (c) with free rOspC and alum; or (d) with adjuvant-free rOspC. Stronger responses are noted with all N'-terminal His-tag rOspC formulations. OspC-specific Th1-type antibodies predominate post-immunization with rOspC proteoliposomes formulated with MPLA or MT06 adjuvants. Further analyses confirmed that the structural features of soluble N' and C' terminal His-tag rOspC and respective rOspC proteoliposomes are similar including their thermal stabilities at physiological temperatures. On the other hand, a change in the position of the rOspC His-tag from N' to C' terminal appears to affect substantially the immunogenicity of rOspC arguably due to steric hindrance of OspC epitopes by the C' terminal His-tag itself and not due to differences in overall conformations induced by changes in the His-tag position in rOspC variants.

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Section: Introductionmentioning

confidence: 99%

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

et al. 2016

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“…Mašek et al ( 2011 ), incorporated rHSP90 into the surface of nickel chelating liposomes associated with norAbuMDP pyrogen adjuvant, a compound of lipophilic derivatives of muramyl dipeptide (MDP), for intradermal vaccination of BALB/c mice and observed comparable Th1 and Th2 response to Freund's complete adjuvant vaccine. Later, Knotigová et al ( 2015 ), evaluated the vaccine efficacy of rHSP90 in nickel-chelating liposomes associated with two pyrogen-free adjuvants (norAbuMDP and norAbuGMDPs) in ICR mice and rabbits, and showed stimulation of innate and adaptive immune response against the rHSP90-containing nano formulation.…”

Section: Current Scenario Of Nanotechnology In the Treatment And Vaccmentioning

confidence: 99%

Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections

Kischkel

Rossi

Santos

et al. 2020

Front. Cell. Infect. Microbiol.

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Treatment modalities for systemic mycoses are still limited. Currently, the main antifungal therapeutics include polyenes, azoles, and echinocandins. However, even in the setting of appropriate administration of antifungals, mortality rates remain unacceptably high. Moreover, antifungal therapy is expensive, treatment periods can range from weeks to years, and toxicity is also a serious concern. In recent years, the increased number of immunocompromised individuals has contributed to the high global incidence of systemic fungal infections. Given the high morbidity and mortality rates, the complexity of treatment strategies, drug toxicity, and the worldwide burden of disease, there is a need for new and efficient therapeutic means to combat invasive mycoses. One promising avenue that is actively being pursued is nanotechnology, to develop new antifungal therapies and efficient vaccines, since it allows for a targeted delivery of drugs and antigens, which can reduce toxicity and treatment costs. The goal of this review is to discuss studies using nanoparticles to develop new therapeutic options, including vaccination methods, to combat systemic mycoses caused by Candida sp., Cryptococcus sp., Paracoccidioides sp., Histoplasma sp., Coccidioides sp., and Aspergillus sp., in addition to providing important information on the use of different types of nanoparticles, nanocarriers and their corresponding mechanisms of action.

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“…Further studies investigated zwitterionic and cationic liposomes utilizing ribosomes and recombinant Hsp90 protein as antigens from C. albicans [ 108 – 110 ]. Eckstein et al prepared anionic DMPC:DMPG liposomes co-lyophilized with RNA obtained from cell lysates of C. albicans cultures or by lipid film formation.…”

Section: Liposomal-based Vaccines In Fungal Infection Treatmentmentioning

confidence: 99%

“…T H 1 and T H 2 immune responses were induced after intradermal mice vaccination in comparable levels to the Freund’s complete adjuvant vaccine. Following the previous report, Knotigová et al employed nickel-chelating liposomes with different MDP-derivatives (norAbuMDP/GMDPs) and tested their adjuvant vaccine potential [ 110 ]. Also, Hsp90 from C. albicans was employed as the model antigen.…”

Section: Liposomal-based Vaccines In Fungal Infection Treatmentmentioning

confidence: 99%

Liposomal vaccine formulations as prophylactic agents: design considerations for modern vaccines

Serrano

Burkhart

2017

J Nanobiotechnol

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Vaccinology is one of the most important cornerstones in modern medicine, providing better quality of life. The human immune system is composed of innate and adaptive immune processes that interplay when infection occurs. Innate immunity relies on pathogen-associated molecular patterns which are recognized by pathogen recognition receptors localized in antigen presenting cells. After antigen processing and presentation, CD4+ T cell polarization occurs, further leading to B cell and CD8+ activation and humoral and cell-mediated adaptive immune responses. Liposomes are being employed as vaccine technologies and their design is of importance to ensure proper immune responses. Physicochemical parameters like liposome size, charge, lamellarity and bilayer fluidity must be completely understood to ensure optimal vaccine stability and efficacy. Liposomal vaccines can be developed to target specific immune cell types for the induction of certain immune responses. In this review, we will present promising liposomal vaccine approaches for the treatment of important viral, bacterial, fungal and parasitic infections (including tuberculosis, TB). Cationic liposomes are the most studied liposome types due to their enhanced interaction with the negatively charged immune cells. Thus, a special section on the cationic lipid dimethyldioctadecylammonium and TB is also presented.

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Molecular Adjuvants Based on Nonpyrogenic Lipophilic Derivatives of norAbuMDP/GMDP Formulated in Nanoliposomes: Stimulation of Innate and Adaptive Immunity

Abstract: Liposomal formulations of new lipophilic derivatives of norAbuMDP/GMDP proved themselves as promising adjuvants for recombinant vaccines as well as immunomodulators for stimulation of innate immunity and bone-marrow recovery after chemo/radio therapy of cancer.

Cited by 19 publications

References 42 publications

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

The Position of His-Tag in Recombinant OspC and Application of Various Adjuvants Affects the Intensity and Quality of Specific Antibody Response after Immunization of Experimental Mice

Therapies and Vaccines Based on Nanoparticles for the Treatment of Systemic Fungal Infections

Liposomal vaccine formulations as prophylactic agents: design considerations for modern vaccines

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