scholarly journals Highly Immunogenic and Protective Recombinant Vaccine Candidate Expressed in Transgenic Plants

2005 ◽  
Vol 73 (9) ◽  
pp. 5915-5922 ◽  
Author(s):  
Daniel Chargelegue ◽  
Pascal M. W. Drake ◽  
Patricia Obregon ◽  
Alessandra Prada ◽  
Neil Fairweather ◽  
...  
Keyword(s):  
Immune Complex ◽  
Tetanus Toxin ◽  
Vaccine Development ◽  
Expression Ratio ◽  
Lethal Challenge ◽  
Alternative Technologies ◽  
Antibody Titers ◽  
Genetic Fusion ◽  
Antigen Presenting ◽  
Immune Complex Formation

ABSTRACT Vaccine development has been hampered by difficulties in developing new and safe adjuvants, so alternative technologies that offer new avenues forward are urgently needed. The goal of this study was to express a monoclonal recombinant immune complex in a transgenic plant. A recombinant protein consisting of a tetanus toxin C fragment-specific monoclonal antibody fused with the tetanus toxin C fragment was designed and expressed. Immune complex formation occurred between individual fusion proteins to form immune complex-like aggregates that bound C1q and FcγRIIa receptor and could be targeted to antigen-presenting cells. Unlike antigen alone, the recombinant immune fusion complexes were highly immunogenic in mice and did not require coadministration of an adjuvant (when injected subcutaneously). Indeed, these complexes elicited antibody titers that were more than 10,000 times higher than those observed in animals immunized with the antigen alone. Furthermore, animals immunized with only 1 μg of recombinant immune complex without adjuvant were fully protected against lethal challenge. This the first report on the use of a genetic fusion between antigen and antibody to ensure an optimal expression ratio between the two moieties and to obtain fully functional recombinant immune complexes as a new vaccine model.

scholarly journals Novel Modified Vaccinia Virus Ankara Vector Expressing Anti-apoptotic GeneB13RDelays Apoptosis and Enhances Humoral Responses

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Lynette S. Chea ◽  
Linda S. Wyatt ◽  
Sailaja Gangadhara ◽  
Bernard Moss ◽  
Rama R. Amara
Keyword(s):  
Vaccinia Virus ◽  
Vaccine Development ◽  
Modified Vaccinia Virus Ankara ◽  
Immunodeficiency Virus ◽  
Antibody Titers ◽  
Infected Cells ◽  
Induced Apoptosis ◽  
Humoral Responses ◽  
Antigen Presenting

ABSTRACTModified vaccinia virus Ankara (MVA), an attenuated poxvirus, has been developed as a potential vaccine vector for use against cancer and multiple infectious diseases, including human immunodeficiency virus (HIV). MVA is highly immunogenic and elicits strong cellular and humoral responses in preclinical models and humans. However, there is potential to further enhance the immunogenicity of MVA, as MVA-infected cells undergo rapid apoptosis, leading to faster clearance of recombinant antigens and potentially blunting a greater response. Here, we generated MVA-B13Rby replacing the fragmented181R/182Rgenes of MVA with a functional anti-apoptotic gene,B13R, and confirmed its anti-apoptotic function against chemically induced apoptosisin vitro. In addition, MVA-B13Rshowed a significant delay in induction of apoptosis in muscle cells derived from mice and humans, as well as in plasmacytoid dendritic cells (pDCs) and CD141+DCs from rhesus macaques, compared to the induction of apoptosis in MVA-infected cells. MVA-B13Rexpressing simian immunodeficiency virus (SIV) Gag and Pol and HIV envelope (SHIV) (MVA-B13R/SHIV) produced higher levels of envelope in the supernatants than MVA/SHIV-infected DF-1 cellsin vitro. Immunization of BALB/c mice showed induction of higher levels of envelope-specific antibody-secreting cells and memory B cells, higher IgG antibody titers, and better persistence of antibody titers with MVA-B13R/SHIV than with MVA/SHIV. Gene set enrichment analysis of draining lymph node cells from day 1 after immunization showed negative enrichment for interferon responses in MVA-B13R/SHIV-immunized mice compared to the responses in MVA/SHIV-immunized mice. Taken together, these results demonstrate that restoringB13Rfunctionality in MVA significantly delays MVA-induced apoptosis in muscle and antigen-presenting cellsin vitroand augments vaccine-induced humoral immunity in mice.IMPORTANCEMVA is an attractive viral vector for vaccine development due to its safety and immunogenicity in multiple species and humans even under conditions of immunodeficiency. Here, to further improve the immunogenicity of MVA, we developed a novel vector, MVA-B13R, by replacing the fragmented anti-apoptotic genes181R/182Rwith a functional version derived from vaccinia virus,B13R. Our results show that MVA-B13Rsignificantly delays apoptosis in antigen-presenting cells and muscle cellsin vitroand augments vaccine-induced humoral immunity in mice, leading to the development of a novel vector for vaccine development against infectious diseases and cancer.

Lactococcus lactis: high-level expression of tetanus toxin fragment C and protection against lethal challenge

1993 ◽  
Vol 8 (6) ◽  
pp. 1155-1162 ◽  
Author(s):  
Jeremy M. Wells ◽  
Peter W. Wilson ◽  
Pamela M. Norton ◽  
Michael J. Gasson ◽  
Richard W. F. Le Page
Keyword(s):  
Lactococcus Lactis ◽  
Tetanus Toxin ◽  
High Level Expression ◽  
Lethal Challenge ◽  
High Level

Effects of Immune Complex Formation and Complement Activation on Circulating Platelets in the Primate

1999 ◽  
Vol 91 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Daniel J. Birmingham ◽  
Lee A. Hebert ◽  
Xiao-Ping Shen ◽  
Paul Higgins ◽  
C.Grace Yeh ◽  
...  
Keyword(s):  
Complex Formation ◽  
Immune Complex ◽  
Complement Activation ◽  
Immune Complex Formation

scholarly journals Towards Quantitative and Standardized Serological and Neutralization Assays for COVID-19

2021 ◽  
Vol 22 (5) ◽  
pp. 2723
Author(s):  
Linhua Tian ◽  
Elzafir B. Elsheikh ◽  
Paul N. Patrone ◽  
Anthony J. Kearsley ◽  
Adolfas K. Gaigalas ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Epidemiologic Studies ◽  
Cross Reactivity ◽  
Receptor Binding Domain ◽  
Proof Of Concept ◽  
Reference Standard ◽  
Improve Measurement ◽  
Antibody Titers

Quantitative and robust serology assays are critical measurements underpinning global COVID-19 response to diagnostic, surveillance, and vaccine development. Here, we report a proof-of-concept approach for the development of quantitative, multiplexed flow cytometry-based serological and neutralization assays. The serology assays test the IgG and IgM against both the full-length spike antigens and the receptor binding domain (RBD) of the spike antigen. Benchmarking against an RBD-specific SARS-CoV IgG reference standard, the anti-SARS-CoV-2 RBD antibody titer was quantified in the range of 37.6 µg/mL to 31.0 ng/mL. The quantitative assays are highly specific with no correlative cross-reactivity with the spike proteins of MERS, SARS1, OC43 and HKU1 viruses. We further demonstrated good correlation between anti-RBD antibody titers and neutralizing antibody titers. The suite of serology and neutralization assays help to improve measurement confidence and are complementary and foundational for clinical and epidemiologic studies.

Antiapoptotic activity maintenance of Brain Derived Neurotrophic Factor and the C fragment of the tetanus toxin genetic fusion protein

2008 ◽  
Vol 3 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Jesús Ciriza ◽  
Marcos García-Ojeda ◽  
Inmaculada Martín-Burriel ◽  
Cendra Agulhon ◽  
Francisco Miana-Mena ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Neurotrophic Factor ◽  
Tetanus Toxin ◽  
Brain Derived Neurotrophic Factor ◽  
Trophic Factors ◽  
Low Concentrations ◽  
Neuro2a Cells ◽  
Genetic Fusion ◽  
The Brain ◽  
Lateral Sclerosis

AbstractNeurotrophic factors have been widely suggested as a treatment for multiple diseases including motorneuron pathologies, like Amyotrophic Lateral Sclerosis. However, clinical trials in which growth factors have been systematically administered to Amyotrophic Lateral Sclerosis patients have not been effective, owing in part to the short half-life of these factors and their low concentrations at target sites. A possible strategy is the use of the atoxic C fragment of the tetanus toxin as a neurotrophic factor carrier to the motorneurons. The activity of trophic factors should be tested because their genetic fusion to proteins could alter their folding and conformation, thus undermining their neuroprotective properties. For this purpose, in this paper we explored the Brain Derived Neurotrophic Factor (BDNF) activity maintenance after genetic fusion with the C fragment of the tetanus toxin. We demonstrated that BDNF fused with the C fragment of the tetanus toxin induces the neuronal survival Akt kinase pathway in mouse cortical culture neurons and maintains its antiapoptotic neuronal activity in Neuro2A cells.

scholarly journals Enhancing Protective Efficacy of Poultry Vaccines through Targeted Delivery of Antigens to Antigen-Presenting Cells

Vaccines ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 75 ◽  
Author(s):  
Angita Shrestha ◽  
Jean-Remy Sadeyen ◽  
Munir Iqbal
Keyword(s):  
B Cells ◽  
Avian Influenza ◽  
Targeted Delivery ◽  
Vaccine Development ◽  
Antigen Presenting Cells ◽  
Influenza Viruses ◽  
Effective Vaccine ◽  
Capture Process ◽  
Selective Delivery ◽  
Antigen Presenting

Avian viral diseases including avian influenza, Marek’s disease and Newcastle disease are detrimental to economies around the world that depend on the poultry trade. A significant zoonotic threat is also posed by avian influenza viruses. Vaccination is an important and widely used method for controlling these poultry diseases. However, the current vaccines do not provide full protection or sterile immunity. Hence, there is a need to develop improved vaccines. The major aim of developing improved vaccines is to induce strong and specific humoral and cellular immunity in vaccinated animals. One strategy used to enhance the immunogenicity of vaccines is the selective delivery of protective antigens to antigen-presenting cells (APCs) including dendritic cells, macrophages and B cells. APCs have a central role in the initiation and maintenance of immune responses through their ability to capture, process and present antigens to T and B cells. Vaccine technology that selectively targets APCs has been achieved by coupling antigens to monoclonal antibodies or ligands that are targeted by APCs. The aim of this review is to discuss existing strategies of selective delivery of antigens to APCs for effective vaccine development in poultry.

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