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https://www.readbyqxmd.com/read/28808204/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#1
Nyamongo Onkoba, Ruth M Mumo, Horace Ochanda, Charles Omwandho, Hastings S Ozwara, Thomas G Egwang
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone...
July 13, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28768668/a-combination-of-recombinant-bcg-expressing-pneumococcal-proteins-induces-cellular-and-humoral-immune-responses-and-protects-against-pneumococcal-colonization-and-sepsis
#2
Cibelly Goulart, Dunia Rodriguez, Alex I Kanno, Thiago Rojas Converso, Ying-Jie Lu, Richard Malley, Luciana C Leite
Pneumococcal diseases remain a substantial cause of mortality in young children in developing countries. The development of potentially serotype-transcending vaccines has been extensively studied; ideally such a vaccine should include antigens that are able to induce protection against colonization (likely mediated by IL-17A) and protection against invasive disease (likely mediated by antibody). The use of strong adjuvants or alternative delivery systems that are able to improve the immunological response of recombinant proteins has been proposed, but poses potential safety and practical concerns in children...
August 2, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28728855/tissue-plasminogen-activator-tpa-signal-sequence-enhances-immunogenicity-of-mva-based-vaccine-against-tuberculosis
#3
Yiming Kou, Yongqing Xu, Zhilei Zhao, Jie Liu, Yang Wu, Qingrui You, Linli Wang, Feng Gao, Linjun Cai, Chunlai Jiang
Tuberculosis (TB) remains a serious health problem worldwide, and the only available vaccine, bacillus Calmette-Guérin (BCG), has shown highly variable efficacy in adults against TB. New vaccines are urgently needed, and the modified vaccinia virus Ankara (MVA)-based vaccine has emerged as one of the most promising candidates based on many preclinical and early clinical studies over the past few years. However, the maximum tolerable dose and strength of induced immune responses have limited the protective effect of MVA-based prophylactic vaccines...
July 17, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28711483/a-multistage-subunit-vaccine-effectively-protects-mice-against-primary-progressive-tuberculosis-latency-and-reactivation
#4
Jilei Ma, Xindong Teng, Xiaochun Wang, Xionglin Fan, Yaqi Wu, Maopeng Tian, Zijie Zhou, Longmeng Li
Adult tuberculosis (TB) is the main cause of TB epidemic and death. The infection results mainly by endogenous reactivation of latent TB infection and secondarily transmitted by exogenous infection. There is no vaccine for adult TB. To this end, we first chose antigens from a potential antigenic reservoir. The antigens strongly recognized T cells from latent and active TB infections that responded to antigens expressed by Mycobacterium tuberculosis cultured under different metabolic states. Fusions of single-stage polyprotein CTT3H, two-stage polyprotein A1D4, and multistage CMFO were constructed...
August 2017: EBioMedicine
https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#5
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28546518/safety-immunogenicity-and-cross-species-protection-of-a-plasmid-dna-encoding-plasmodium-falciparum-sera5-polypeptide-microbial-epitopes-and-chemokine-genes-in-mice-and-olive-baboons
#6
Nyamongo Onkoba, Ruth M Mumo, Horace Ochanda, Charles Omwandho, Hastings S Ozwara, Thomas G Egwang
Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of strain-transcending malarial vaccines. The present study sought to determine safety, immunogenicity and cross-species efficacy ofPlasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of Bacille-Calmette Guerin (BCG), tetanus toxoid (TT) and a chemokine gene. Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups. The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5+ BCG+ TT alone, or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone...
April 6, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28498853/safety-and-immunogenicity-of-an-inactivated-whole-cell-tuberculosis-vaccine-booster-in-adults-primed-with-bcg-a-randomized-controlled-trial-of-dar-901
#7
C Fordham von Reyn, Timothy Lahey, Robert D Arbeit, Bernard Landry, Leway Kailani, Lisa V Adams, Brenda C Haynes, Todd Mackenzie, Wendy Wieland-Alter, Ruth I Connor, Sue Tvaroha, David A Hokey, Ann M Ginsberg, Richard Waddell
BACKGROUND: Development of a tuberculosis vaccine to boost BCG is a major international health priority. SRL172, an inactivated whole cell booster derived from a non-tuberculous mycobacterium, is the only new vaccine against tuberculosis to have demonstrated efficacy in a Phase 3 trial. In the present study we sought to determine if a three-dose series of DAR-901 manufactured from the SRL172 master cell bank by a new, scalable method was safe and immunogenic. METHODS: We performed a single site, randomized, double-blind, controlled, Phase 1 dose escalation trial of DAR-901 at Dartmouth-Hitchcock Medical Center in the United States...
2017: PloS One
https://www.readbyqxmd.com/read/28476627/-the-impact-of-mycobacterium-tuberculosis-immune-evasion-on-protective-immunity-implications-for-tb-vaccine-design-meeting-report
#8
Cesar Boggiano, Katrin Eichelberg, Lakshmi Ramachandra, Jaqueline Shea, Lalita Ramakrishnan, Samuel Behar, Joel D Ernst, Steven A Porcelli, Markus Maeurer, Hardy Kornfeld
Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB...
June 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28453555/multi-subunit-bcg-booster-vaccine-gamtbvac-assessment-of-immunogenicity-and-protective-efficacy-in-murine-and-guinea-pig-tb-models
#9
A P Tkachuk, V A Gushchin, V D Potapov, A V Demidenko, V G Lunin, A L Gintsburg
New innovative vaccines are highly needed to combat the global threat posed by tuberculosis. Efficient components-antigens and adjuvants-are crucial for development of modern recombinant TB vaccines. This study describes a new vaccine (GamTBvac) consisting of two mycobacterial antigen fusions (Ag85A and ESAT6-CFP10)-with dextran-binding domain immobilized on dextran and mixed with an adjuvant consisting of DEAE-dextran core, and with CpG oligodeoxynucleotides (TLR9 agonists). GamTBvac and its components were assessed for immunogenicity and protective efficacy in GamTBvac-prime/boost and BCG-prime/ GamTBvac-boost in murine and guinea pig TB models...
2017: PloS One
https://www.readbyqxmd.com/read/28426273/preclinical-development-of-bcg-hiva-2auxo-int-harboring-an-integrative-expression-vector-for-a-hiv-tb-pediatric-vaccine-enhancement-of-stability-and-specific-hiv-1-t-cell-immunity
#10
Aakash Mahant, Narcís Saubi, Yoshiki Eto, Núria Guitart, Josep Ma Gatell, Tomáš Hanke, Joan Joseph
One of the critical issues that should be addressed in the development of a BCG-based HIV vaccine is genetic plasmid stability. Therefore, to address this issue we have considered using integrative vectors and the auxotrophic mutant of BCG complemented with a plasmid carrying a wild-type complementing gene. In this study, we have constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HIVA(int), expressing the HIV-1 clade A immunogen HIVA. This shuttle vector uses an antibiotic resistance-free mechanism for plasmid selection and maintenance...
August 3, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28342639/sendai-virus-mucosal-vaccination-establishes-lung-resident-memory-cd8%C3%A2-t-cell-immunity-and-boosts-bcg-primed-protection-against-tb-in-mice
#11
Zhidong Hu, Ka-Wing Wong, Hui-Min Zhao, Han-Li Wen, Ping Ji, Hui Ma, Kang Wu, Shui-Hua Lu, Feng Li, Zhong-Ming Li, Tsugumine Shu, Jian-Qing Xu, Douglas B Lowrie, Xiao-Yong Fan
Accumulating evidence has shown the protective role of CD8(+) T cells in vaccine-induced immunity against Mycobacterium tuberculosis (Mtb) despite controversy over their role in natural immunity. However, the current vaccine BCG is unable to induce sufficient CD8(+) T cell responses, especially in the lung. Sendai virus, a respiratory RNA virus, is here engineered firstly as a novel recombinant anti-TB vaccine (SeV85AB) that encodes Mtb immuno-dominant antigens, Ag85A and Ag85B. A single mucosal vaccination elicited potent antigen-specific T cell responses and a degree of protection against Mtb challenge similar to the effect of BCG in mice...
May 3, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28329234/revaccination-of-guinea-pigs-with-the-live-attenuated-mycobacterium-tuberculosis-vaccine-mtbvac-improves-bcg-s-protection-against-tuberculosis
#12
Simon Clark, Faye Lanni, Dessislava Marinova, Emma Rayner, Carlos Martin, Ann Williams
Background: The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. Methods: In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared...
January 25, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28314076/lactococcus-lactis-carrying-a-dna-vaccine-coding-for-the-esat-6-antigen-increases-il-17-cytokine-secretion-and-boosts-the-bcg-vaccine-immune-response
#13
V B Pereira, V P da Cunha, T M Preisser, B M Souza, M Z Turk, C P De Castro, M S P Azevedo, A Miyoshi
AIMS: A regimen utilizing Bacille Calmette-Guerin (BCG) and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis fibronectin-binding protein A (FnBPA+) (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In this study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice...
March 17, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28293387/cfp10-mfc%C3%AE-2-as-a-novel-tuberculosis-vaccine-candidate-increases-immune-response-in-mouse
#14
Ali Asghar Baghani, Saman Soleimanpour, Hadi Farsiani, Arman Mosavat, Masoud Yousefi, Zahra Meshkat, Seyed Abdolrahim Rezaee, Saeid Amel Jamehdar, Mohammad Reza Akbari Eydgahi, Hamid Sadeghian, Kiarash Ghazvini
OBJECTIVES: Despite treatment with antibiotics and vaccination with BCG, tuberculosis (TB) is still considered as one of the most important public health problems in the world. Therefore, designing and producing a more effective vaccine against TB seems urgently. In this study, immunogenicity of a fusion protein which consisting or comprising CFP-10 from Mycobacterium tuberculosis and the Fc-domain of mouse IgG2a was evaluated as a novel subunit vaccine candidate against TB. MATERIALS AND METHODS: The genetic constructs were cloned in pPICZαA expression vector and recombinant vectors (pPICZαA-CFP-10: Fcγ2a and pPICZαA-CFP-10:His) were transformed into Pichia pastoris...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28278263/heterologous-prime-boost-vaccination-with-dna-and-mva-vaccines-expressing-hiv-1-subtype-c-mosaic-gag-virus-like-particles-is-highly-immunogenic-in-mice
#15
Ros Chapman, Tsungai Ivai Jongwe, Nicola Douglass, Gerald Chege, Anna-Lise Williamson
In an effort to make affordable vaccines suitable for the regions most affected by HIV-1, we have constructed stable vaccines that express an HIV-1 subtype C mosaic Gag immunogen (BCG-GagM, MVA-GagM and DNA-GagM). Mosaic immunogens have been designed to address the tremendous diversity of this virus. Here we have shown that GagM buds from cells infected and transfected with MVA-GagM and DNA-GagM respectively and forms virus-like particles. Previously we showed that a BCG-GagM prime MVA-GagM boost generated strong cellular immune responses in mice...
2017: PloS One
https://www.readbyqxmd.com/read/28242071/recombinant-bcg-expressing-a-pspa-pdt-fusion-protein-protects-mice-against-pneumococcal-lethal-challenge-in-a-prime-boost-strategy
#16
Cibelly Goulart, Dunia Rodriguez, Alex I Kanno, Ying-Jie Lu, Richard Malley, Luciana C C Leite
Pneumococcal proteins have been evaluated as genetically-conserved potential vaccine candidates. We have previously demonstrated that a fragment of PspA in fusion with PdT (rPspA-PdT) induced protective immune responses in mice. However, purified proteins have shown poor immunogenicity and often require the combination with strong adjuvants and booster doses. Here, we investigated the use of a Bacillus Calmette-Guérin (BCG) strain, a well-established prophylactic vaccine for tuberculosis with known adjuvant properties, for delivery of the PspA-PdT fusion protein...
March 23, 2017: Vaccine
https://www.readbyqxmd.com/read/28161464/mycobacterium-tuberculosis-proteins-involved-in-cell-wall-lipid-biosynthesis-improve-bcg-vaccine-efficacy-in-a-murine-tb-model
#17
REVIEW
Martin Rao, Nathalie Cadieux, Megan Fitzpatrick, Steven Reed, Sergei Arsenian, Davide Valentini, Shreemanta Parida, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
OBJECTIVES: Advances in tuberculosis (TB) vaccine development are urgently required to enhance global disease management. We evaluated the potential of Mycobacterium tuberculosis (M. tb)-derived protein antigens Rv0447c, Rv2957 and Rv2958c to boost BCG vaccine efficacy in the presence or absence of glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) adjuvant. METHODS: Mice received the BCG vaccine, followed by Rv0447c, Rv2957 and Rv2958c protein boosting with or without GLA-SE adjuvant 3 and 6 weeks later...
March 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28123491/ag85b-synergizes-with-esat-6-to-induce-efficient-and-long-term-immunity-of-c57bl-6-mice-primed-with-recombinant-bacille-calmette-guerin
#18
Wei Liu, Ying Xu, Jingran Yan, Hongbo Shen, Enzhuo Yang, Honghai Wang
The latest probable scenario in vaccination strategies is to prime one live attenuated vaccine candidate followed by boost dose of second vaccine candidate. In the present study, we primed the mice with a recombinant Bacille Calmette-Guerin (BCG) comprising Ag85B and ESAT-6 followed by boost doses of Ag85B, ESAT-6 and Ag85B-ESAT-6 fusion protein in the DDA adjuvant, separately. After boost doses of 8 and 12 weeks, the levels of antigen-stimulated T cells secreting interferon (IFN)-γ, the content of the IFN-γ, tumor necrosis factor-α and interleukin-4 in the splenocytes in vitro culture supernatant, the antigen-specific immunoglobulin (Ig)G titer from mouse serum, IgG subclass and the population of antigen-specific CD4(+) and CD8(+) T cells were detected...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28087924/clinical-testing-of-tuberculosis-vaccine-candidates
#19
Mark Hatherill, Dereck Tait, Helen McShane
It is almost 100 years since the development of bacille Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis (TB). While BCG does confer consistent protection against disseminated disease, there is an urgent need for a more effective vaccine against pulmonary disease. There are several indications for such an improved vaccine, including prevention of infection, prevention of disease, and a therapeutic vaccine to prevent recurrent disease. The two main approaches to TB vaccine development are developing an improved whole mycobacterial priming agent to replace BCG and/or developing a subunit booster vaccine to be administered after a BCG or BCG replacement priming vaccination...
October 2016: Microbiology Spectrum
https://www.readbyqxmd.com/read/28011813/does-oral-polio-vaccine-have-non-specific-effects-on-all-cause-mortality-natural-experiments-within-a-randomised-controlled-trial-of-early-measles-vaccine
#20
Peter Aaby, Andreas Andersen, Cesário L Martins, Ane B Fisker, Amabelia Rodrigues, Hilton C Whittle, Christine S Benn
BACKGROUND: BCG and measles vaccine (MV) may have beneficial non-specific effects (NSEs). If an unplanned intervention with a vaccine (a natural experiment) modifies the estimated effect in a randomised controlled trial (RCT), this suggests NSEs. We used this approach to test NSEs of triple oral polio vaccine (OPV). METHODS: During an RCT of 2 doses of MV at 4.5 and 9 months versus 1 dose of MV at 9 months of age, we experienced 2 natural experiments with OPV...
December 23, 2016: BMJ Open
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