LIVIVO - The Search Portal for Life Sciences

zur deutschen Oberfläche wechseln
Advanced search

Search results

Result 1 - 10 of total 49

Search options

  1. Article ; Online: Maintaining immunogenicity of blood stage and sexual stage subunit malaria vaccines when formulated in combination.

    Elizabeth M Parzych / Kazutoyo Miura / Carole A Long / James M Burns

    PLoS ONE, Vol 15, Iss 4, p e

    2020  Volume 0232355

    Abstract: BACKGROUND:Eradication of Plasmodium falciparum malaria will likely require a multivalent vaccine, but the development of a highly efficacious subunit-based formulation has been challenging. We previously showed that production and immunogenicity of two ... ...

    Abstract BACKGROUND:Eradication of Plasmodium falciparum malaria will likely require a multivalent vaccine, but the development of a highly efficacious subunit-based formulation has been challenging. We previously showed that production and immunogenicity of two leading vaccine targets, PfMSP119 (blood-stage) and Pfs25 (sexual stage), could be enhanced upon genetic fusion to merozoite surface protein 8 (PfMSP8). Here, we sought to optimize a Pfs25-based formulation for use in combination with rPfMSP1/8 with the goal of maintaining the immunogenicity of each subunit. METHODS:Comparative mouse studies were conducted to assess the effects of adjuvant selection (Alhydrogel vs. glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE)) and antigen dose (2.5 vs. 0.5 μg) on the induction of anti-Pfs25 immune responses. The antibody response (magnitude, IgG subclass profile, and transmission-reducing activity (TRA)) and cellular responses (proliferation, cytokine production) generated in response to each formulation were assessed. Similarly, immunogenicity of a bivalent vaccine containing rPfMSP1/8 and rPfs25/8 was evaluated. RESULTS:Alum-based formulations elicited strong and comparable humoral and cellular responses regardless of antigen form (unfused rPfs25 or chimeric rPfs25/8) or dose. In contrast, GLA-SE based formulations elicited differential responses as a function of both parameters, with 2.5 μg of rPfs25/8 inducing the highest titers of functional anti-Pfs25 antibodies. Based on these data, chimeric rPfs25/8 was selected and tested in a bivalent formulation with rPfMSP1/8. Strong antibody titers against Pfs25 and PfMSP119 domains were induced with GLA-SE based formulations, with no indication of antigenic competition. CONCLUSIONS:We were able to generate an immunogenic bivalent vaccine designed to target multiple parasite stages that could reduce both clinical disease and parasite transmission. The use of the same PfMSP8 carrier for two different vaccine components was effective in this bivalent formulation. As such, the ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  2. Article ; Online: A Plant-Produced in vivo deglycosylated full-length Pfs48/45 as a Transmission-Blocking Vaccine Candidate against malaria

    Tarlan Mamedov / Kader Cicek / Kazutoyo Miura / Burcu Gulec / Ersin Akinci / Gunay Mammadova / Gulnara Hasanova

    Scientific Reports, Vol 9, Iss 1, Pp 1-

    2019  Volume 12

    Abstract: Abstract Pfs48/45 is a leading antigen candidate for a transmission blocking (TB) vaccine. However, efforts to produce affordable, safe and correctly folded full-length Pfs48/45 using different protein expression systems have not produced an antigen with ...

    Abstract Abstract Pfs48/45 is a leading antigen candidate for a transmission blocking (TB) vaccine. However, efforts to produce affordable, safe and correctly folded full-length Pfs48/45 using different protein expression systems have not produced an antigen with satisfactory TB activity. Pfs48/45 has 16 cysteines involved in disulfide bond formation, and the correct formation is critical for proper folding and induction of TB antibodies. Moreover, Pfs48⁄45 is not a glycoprotein in the native hosts, but contains potential glycosylation sites, which are aberrantly glycosylated during expression in eukaryotic systems. Here, we demonstrate for the first time that full length, Endo H in vivo enzymatic deglycosylated Pfs48/45 antigen is produced at a high level in plants and is structurally stable at elevated temperatures. Sera from mice immunized with this antigen showed strong inhibition in SMFA. Thus, Endo H in vivo enzymatic deglycosylated Pfs48/45 is a promising candidate for the development of an affordable TB vaccine, which may have the potential to save millions.
    Keywords Medicine ; R ; Science ; Q
    Subject code 570
    Language English
    Publishing date 2019-07-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  3. Article ; Online: Evaluation and modeling of direct membrane-feeding assay with Plasmodium vivax to support development of transmission blocking vaccines

    Kazutoyo Miura / Bruce J. Swihart / Michael P. Fay / Chalermpon Kumpitak / Kirakorn Kiattibutr / Jetsumon Sattabongkot / Carole A. Long

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Abstract Standard and direct membrane-feeding assays (SMFA and DMFA) are fundamental assays to evaluate efficacy of transmission-blocking intervention (TBI) candidates against Plasmodium falciparum and vivax. To compare different candidates precisely, it ...

    Abstract Abstract Standard and direct membrane-feeding assays (SMFA and DMFA) are fundamental assays to evaluate efficacy of transmission-blocking intervention (TBI) candidates against Plasmodium falciparum and vivax. To compare different candidates precisely, it is crucial to understand the error range of measured activity, usually expressed as percent inhibition in either oocyst intensity (% transmission reducing activity, %TRA), or in prevalence of infected mosquitoes (% transmission blocking activity, %TBA). To this end, mathematical models have been proposed for P. falciparum SMFA (PfSMFA), but such study for DMFA is limited. In this study, we analyzed P. vivax DMFA (PvDMFA) data from 22,236 mosquitoes tested from 96 independent assays. While the two assays are quite different, a zero-inflated negative binomial (ZINB) model could reasonably explain the PvDMFA results, as it has for PfSMFA. Our simulation studies based on the ZINB model revealed it is better to report %TRA values with a proper error range, rather than observed %TBA both in SMFA and DMFA. Furthermore, the simulations help in designing a better assay and aid in estimating an error range of a %TRA value when the uncertainty is not reported. This study strongly supports future TBI development by providing a rational method to compare different candidates.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  4. Article ; Online: A C-terminal Pfs48/45 malaria transmission-blocking vaccine candidate produced in the baculovirus expression system

    Shwu-Maan Lee / John M. Hickey / Kazutoyo Miura / Sangeeta B. Joshi / David B. Volkin / C. Richter King / Jordan L. Plieskatt

    Scientific Reports, Vol 10, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Abstract The Plasmodium falciparum gametocyte surface protein, Pfs48/45, is a potential target for malaria transmission-blocking vaccines. However, due to its size and complexity, expression of the full-length protein has been difficult, leading to focus ...

    Abstract Abstract The Plasmodium falciparum gametocyte surface protein, Pfs48/45, is a potential target for malaria transmission-blocking vaccines. However, due to its size and complexity, expression of the full-length protein has been difficult, leading to focus on the C-terminal six cysteine domain (6C) with the use of fusion proteins to facilitate expression and folding. In this study, we utilized the baculovirus system to evaluate the expression of three Pfs48/45 proteins including the full-length protein, the 6C domain fragment and the 6C domain mutant to prevent glycosylation. Expression of the recombinant Pfs48/45 proteins was conducted in super Sf9 cells combined with the use of tunicamycin to prevent N-glycosylation. The proteins were then evaluated as immunogens in mice to demonstrate the induction of functionally active polyclonal antibody responses as measured in the standard membrane feeding assay (SMFA). Only the 6C protein was found to exhibit significant transmission-reducing activity. Further characterization of the biologically active 6C protein demonstrated it was homogeneous in terms of size, charge, conformation, absence of glycosylation, and containing proper disulfide bond pairings. This study presents an alternative expression system, without the need of a fusion protein partner, for the Pfs48/45 6C protein fragment including further evaluation as a potential transmission-blocking vaccine candidate.
    Keywords Medicine ; R ; Science ; Q
    Subject code 500
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  5. Article ; Online: Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose

    Wei-Chiao Huang / Bingbing Deng / Moustafa T. Mabrouk / Amal Seffouh / Joaquin Ortega / Carole Long / Kazutoyo Miura / Yimin Wu / Jonathan F. Lovell

    Malaria Journal, Vol 19, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Abstract Background The Plasmodium falciparum sexual-stage surface proteins Pfs25 and Pfs230 are antigen candidates for a malaria transmission-blocking vaccine (TBV), and have been widely investigated as such. It is not clear whether simultaneously ... ...

    Abstract Abstract Background The Plasmodium falciparum sexual-stage surface proteins Pfs25 and Pfs230 are antigen candidates for a malaria transmission-blocking vaccine (TBV), and have been widely investigated as such. It is not clear whether simultaneously presenting these two antigens in a particulate vaccine would enhance the transmission reducing activity (TRA) of induced antibodies. To assess this, immunization was carried out with liposomes containing synthetic lipid adjuvant monophosphoryl lipid A (MPLA), and cobalt-porphyrin-phospholipid (CoPoP), which rapidly converts recombinant, his-tagged antigens into particles. Methods His-tagged, recombinant Pfs25 and Pfs230C1 were mixed with CoPoP liposomes to form a bivalent vaccine. Antigens were fluorescently labelled to infer duplex particleization serum-stability and binding kinetics using fluorescence resonance energy transfer. Mice and rabbits were immunized with individual or duplexed particleized Pfs25 and Pfs230C1, at fixed total antigen doses. The resulting antibody responses were assessed for magnitude and TRA. Results Pfs230C1 and Pfs25 rapidly bound CoPoP liposomes to form a serum-stable, bivalent particle vaccine. In mice, immunization with 5 ng of total antigen (individual antigen or duplexed) elicited functional antibodies against Pfs25 and Pfs230. Compared to immunization with the individual antigen, Pfs25 antibody production was moderately lower for the bivalent CoPoP vaccine, whereas Pfs230C1 antibody production was not impacted. All antibodies demonstrated at least 92% inhibition in oocyst density at 750 μg/mL purified mouse IgG in the standard membrane feeding assay (SMFA). At lower IgG concentrations, the bivalent vaccine did not improve TRA; antibodies induced by particleized Pfs25 alone showed stronger function in these conditions. In rabbits, immunization with a 20 µg total antigen dose with the duplexed antigens yielded similar antibody production against Pfs25 and Pfs230 compared to immunization with a 20 µg dose of individual antigens. ...
    Keywords Pfs25 ; Pfs230 ; Malaria ; Transmission-blocking vaccine ; Liposomes ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Subject code 630 ; 616
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  6. Article ; Online: Orientation of Antigen Display on Self-Assembling Protein Nanoparticles Influences Immunogenicity

    Cosette G. Schneider / Justin A. Taylor / Michael Q. Sibilo / Kazutoyo Miura / Katherine L. Mallory / Christopher Mann / Christopher Karch / Zoltan Beck / Gary R. Matyas / Carole A. Long / Elke Bergmann-Leitner / Peter Burkhard / Evelina Angov

    Vaccines, Vol 9, Iss 2, p

    2021  Volume 103

    Abstract: Self-assembling protein nanoparticles (SAPN) serve as a repetitive antigen delivery platform with high-density epitope display; however, antigen characteristics such as size and epitope presentation can influence the immunogenicity of the assembled ... ...

    Abstract Self-assembling protein nanoparticles (SAPN) serve as a repetitive antigen delivery platform with high-density epitope display; however, antigen characteristics such as size and epitope presentation can influence the immunogenicity of the assembled particle and are aspects to consider for a rationally designed effective vaccine. Here, we characterize the folding and immunogenicity of heterogeneous antigen display by integrating (a) dual-stage antigen SAPN presenting the P. falciparum ( Pf ) merozoite surface protein 1 subunit, PfMSP1 19 , and Pf cell-traversal protein for ookinetes and sporozoites, PfCelTOS, in addition to (b) a homogenous antigen SAPN displaying two copies of PfCelTOS. Mice and rabbits were utilized to evaluate antigen-specific humoral and cellular induction as well as functional antibodies via growth inhibition of the blood-stage parasite. We demonstrate that antigen orientation and folding influence the elicited immune response, and when appropriately designed, SAPN can serve as an adaptable platform for an effective multi-antigen display.
    Keywords self-assembling protein nanoparticles ; PfCelTOS ; PfMSP1 19 ; vaccine ; multi-stage ; display ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  7. Article ; Online: Interim analysis from a phase 2 randomized trial of EuCorVac-19

    Jonathan F. Lovell / Yeong Ok Baik / Seuk Keun Choi / Chankyu Lee / Jeong-Yoon Lee / Kazutoyo Miura / Wei-Chiao Huang / Young-Shin Park / Sun-Je Woo / Sang Hwan Seo / Jae-Ouk Kim / Manki Song / Chung-Jong Kim / Jae-Ki Choi / Jieun Kim / Eun Ju Choo / Jung-Hyun Choi

    BMC Medicine, Vol 20, Iss 1, Pp 1-

    a recombinant protein SARS-CoV-2 RBD nanoliposome vaccine

    2022  Volume 11

    Abstract: Abstract Background Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on ... ...

    Abstract Abstract Background Numerous vaccine strategies are being advanced to control SARS-CoV-2, the cause of the COVID-19 pandemic. EuCorVac-19 (ECV19) is a recombinant protein nanoparticle vaccine that displays the SARS-CoV-2 receptor-binding domain (RBD) on immunogenic nanoliposomes. Methods Initial study of a phase 2 randomized, observer-blind, placebo-controlled trial to assess the immunogenicity, safety, and tolerance of ECV19 was carried out between July and October 2021. Two hundred twenty-nine participants were enrolled at 5 hospital sites in South Korea. Healthy adults aged 19–75 without prior known exposure to COVID-19 were vaccinated intramuscularly on day 0 and day 21. Of the participants who received two vaccine doses according to protocol, 100 received high-dose ECV19 (20 μg RBD), 96 received low-dose ECV19 (10 μg RBD), and 27 received placebo. Local and systemic adverse events were monitored. Serum was assessed on days 0, 21, and 42 for immunogenicity analysis by ELISA and neutralizing antibody response by focus reduction neutralization test (FRNT). Results Low-grade injection site tenderness and pain were observed in most participants. Solicited systemic adverse events were less frequent, and mostly involved low-grade fatigue/malaise, myalgia, and headache. No clinical laboratory abnormalities were observed. Adverse events did not increase with the second injection and no serious adverse events were solicited by ECV19. On day 42, Spike IgG geometric mean ELISA titers were 0.8, 211, and 590 Spike binding antibody units (BAU/mL) for placebo, low-dose and high-dose ECV19, respectively (p < 0.001 between groups). Neutralizing antibodies levels of the low-dose and high-dose ECV19 groups had FRNT50 geometric mean values of 129 and 316, respectively. Boosting responses and dose responses were observed. Antibodies against the RBD correlated with antibodies against the Spike and with virus neutralization. Conclusions ECV19 was generally well-tolerated and induced antibodies in a dose-dependent manner that ...
    Keywords COVID-19 ; SARS-CoV-2 ; RBD ; Vaccine ; Liposome ; Adjuvant ; Medicine ; R
    Subject code 630
    Language English
    Publishing date 2022-11-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  8. Article ; Online: Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages

    Wei-Chiao Huang / Moustafa T. Mabrouk / Luwen Zhou / Minami Baba / Mayumi Tachibana / Motomi Torii / Eizo Takashima / Emily Locke / Jordan Plieskatt / C. Richter King / Camila H. Coelho / Patrick E. Duffy / Carole Long / Takafumi Tsuboi / Kazutoyo Miura / Yimin Wu / Tomoko Ishino / Jonathan F. Lovell

    Communications Biology, Vol 5, Iss 1, Pp 1-

    2022  Volume 13

    Abstract: Co-display of two P. falciparum malaria vaccine antigens (Pfs230D1+ and CSP) on the surface of immunogenic liposomes results in functional immune responses upon immunization of mice and rabbits. Combining both antigens produces immune responses that both ...

    Abstract Co-display of two P. falciparum malaria vaccine antigens (Pfs230D1+ and CSP) on the surface of immunogenic liposomes results in functional immune responses upon immunization of mice and rabbits. Combining both antigens produces immune responses that both block transmission and prevent infection.
    Keywords Biology (General) ; QH301-705.5
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  9. Article ; Online: Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine

    Carolyn M. Nielsen / Jordan R. Barrett / Christine Davis / Jonathan K. Fallon / Cyndi Goh / Ashlin R. Michell / Catherine Griffin / Andrew Kwok / Carolin Loos / Samuel Darko / Farida Laboune / Mehmet Tekman / Ababacar Diouf / Kazutoyo Miura / Joseph R. Francica / Amy Ransier / Carole A. Long / Sarah E. Silk / Ruth O. Payne /
    Angela M. Minassian / Douglas A. Lauffenburger / Robert A. Seder / Daniel C. Douek / Galit Alter / Simon J. Draper

    JCI Insight, Vol 8, Iss

    2023  Volume 2

    Abstract: Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01B-adjuvanted RH5.1 malaria antigen — ...

    Abstract Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) — using AS01B-adjuvanted RH5.1 malaria antigen — substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.
    Keywords Immunology ; Vaccines ; Medicine ; R
    Subject code 571
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher American Society for Clinical investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

  10. Article ; Online: Harmonization study between three laboratories for expression of malaria vaccine clinical trial IgG antibody ELISA data in µg/mL

    Geneviève M. Labbé / Kazutoyo Miura / Sarah E. Silk / Wenjuan Gu / James E. Moon / Jing Jin / Ruth O. Payne / Michael P. Fay / Sheetij Dutta / Carole A. Long / Simon J. Draper

    Malaria Journal, Vol 18, Iss 1, Pp 1-

    2019  Volume 9

    Abstract: Abstract Background The ability to report vaccine-induced IgG responses in terms of µg/mL, as opposed arbitrary units (AU), enables a more informed interpretation of the magnitude of the immune response, and better comparison between vaccines targeting ... ...

    Abstract Abstract Background The ability to report vaccine-induced IgG responses in terms of µg/mL, as opposed arbitrary units (AU), enables a more informed interpretation of the magnitude of the immune response, and better comparison between vaccines targeting different antigens. However, these interpretations rely on the accuracy of the methodology, which is used to generate ELISA data in µg/mL. In a previous clinical trial of a vaccine targeting the apical membrane antigen 1 (AMA1) from Plasmodium falciparum, three laboratories (Oxford, NIH and WRAIR) reported ELISA data in µg/mL that were correlated but not concordant. This current study sought to harmonize the methodology used to generate a conversion factor (CF) for ELISA analysis of human anti-AMA1 IgG responses across the three laboratories. Methods Purified IgG was distributed to the three laboratories and, following a set protocol provided by NIH, AMA1-specific human IgG was affinity purified. A new “harmonized CF” was generated by each laboratory using their in-house ELISA, and the original clinical trial ELISA data were re-analysed accordingly. Results Statistical analysis showed that the data remained highly correlated across all three laboratories, although only Oxford and NIH were able to harmonize their CF for ELISA and generate concordant data. Conclusions This study enabled two out of the three laboratories to harmonize their µg/mL readouts for the human anti-AMA1 IgG ELISA, but results reported from WRAIR are ~ twofold higher. Given the need to validate such information for each species and antigen of interest, it is important to bear in mind these likely differences when interpreting µg/mL ELISA data in the future.
    Keywords Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Language English
    Publishing date 2019-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

    Kategorien

To top