scholarly journals Clinical Studies of Vaccine Against Smallpox on the Base of Recombinant Vaccinia b7,5S2-S Strain under the Conditions of Double Oral Vaccination

2010 ◽  
pp. 51-55
Author(s):  
I. V. Plyasunov ◽  
A. A. Sergeev ◽  
L. N. Shishkina ◽  
Al. A. Sergeev ◽  
K. A. Titova ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Clinical Manifestation ◽  
Clinical Studies ◽  
Small Dose ◽  
Neutralizing Antibodies ◽  
Protective Level ◽  
Oral Vaccination

Volunteers who had been vaccinated against smallpox in their childhood were orally immunized with Revax-BT vaccine - initially with a small dose, then (in 7, 14, 30, 90 and 180 days) with a large one. Slight reactogenicity was observed after the first vaccination whereas revaccination induced no clinical manifestation. Double immunization with this preparation with 1-2 weeks interval proved to be the most effective method: the protective level of virus-neutralizing antibodies to vaccinia virus (VV) was formed in 90-100 % volunteers in a month after vaccination, and 6 months later this index decreased up to 70 %. The recombinant VV was not registered in the samples of blood, saliva and urine taken from the volunteers after double immunization.

scholarly journals Maternal transfer of neutralizing antibodies to B. burgdorferi OspA after oral vaccination of the rodent reservoir

Vaccine ◽  
2021 ◽  
Author(s):  
Kathryn Phillip ◽  
Nisha Nair ◽  
Kamalika Samanta ◽  
Jose F. Azevedo ◽  
Grant D. Brown ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Maternal Transfer ◽  
Oral Vaccination

scholarly journals 716 Cell-based virotherapy for targeting cancers

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A758-A758
Author(s):  
Duong Nguyen ◽  
Alberto Gomez ◽  
Forrest Neuharth ◽  
Ashley Alamillo ◽  
Thomas Herrmann ◽  
...  
Keyword(s):  
Stem Cells ◽  
Vaccinia Virus ◽  
Cancer Cells ◽  
Neutralizing Antibodies ◽  
Immune Cell ◽  
Human Cancer ◽  
Oncolytic Viruses ◽  
Oncolytic Virotherapy ◽  
Adaptive Immune ◽  
Immune Barriers

BackgroundOncolytic virotherapy has been recognized as a promising new therapy for cancer for decades but only few viruses have been approved worldwide. The therapeutic potential of oncolytic viruses can be severely restricted by innate and adaptive immune barriers making oncolytic virus clinically inefficient. To overcome this obstacle, we utilized adipose-derived stem cells (AD-MSC) loaded with tumor selective CAL1 oncolytic vaccinia virus to generate a new therapeutic agent called SNV1 (SuperNova-1).MethodsCAL1 vaccinia virus was tested for its ability to replicate and selectively kill various human cancer cell lines in vitro and in vivo. Additionally, CAL1 was loaded into adipose-derived mesenchymal stem cells to generate SuperNova1 (SNV1). Both CAL1 and SNV1 were tested for their ability to kill cancer cells in the presence of active complement and neutralizing antibodies in cell culture as well as in mice. Immune cell infiltration of the treated and untreated tumors was analyzed by flow cytometry.ResultsCAL1 showed preferential amplification and killed various tested human (PC3, FaDu, MDA-MB-231, RPMI) and mouse cancer cells (CT26, EMT6, TRAMP-C2, RM1). In animals, CAL1 caused tumor regression in PC3 and CT26 mouse models without signs of toxicity. SNV1 significantly enhanced protection of CAL1 virus from clearance by the immune system as compared to naked CAL1 virus, leading to higher therapeutic efficacy in animals. Five days after SNV1 administration, tumor infiltrating lymphocytes (TILs) from both treated and untreated tumors showed increased CD4 and CD8 T-cell infiltrations. Importantly, we documented a decreased frequency of Tregs, and improved effector to Treg ratios, which was associated with inhibition of tumor growth at the treated tumor site and also at distant untreated sites.ConclusionsCAL1 is potentially used as an oncolytic agent. In addition, SNV1 cell-based platform protects and potentiates oncolytic vaccinia virus by circumventing humoral innate and adaptive immune barriers, resulting in enhanced oncolytic virotherapy. Particularly, SNV1 provided instantly active viral particles for immediate infection and simultaneous release of therapeutic proteins in the injected tumors.

scholarly journals Persisting Humoral Antiviral Immunity within the Japanese Population after the Discontinuation in 1976 of Routine Smallpox Vaccinations

2005 ◽  
Vol 12 (4) ◽  
pp. 520-524 ◽  
Author(s):  
Shuji Hatakeyama ◽  
Kyoji Moriya ◽  
Masayuki Saijo ◽  
Yuji Morisawa ◽  
Ichiro Kurane ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Japanese Population ◽  
Neutralizing Antibodies ◽  
Antiviral Immunity ◽  
Smallpox Vaccination ◽  
Considerable Proportion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Immunoglobulin ◽  
Specific Igg ◽  
Induced Immunity

ABSTRACT Concerns have arisen recently about the possible use of smallpox for a bioterrorism attack. Routine smallpox vaccination was discontinued in Japan in 1976; however, it is uncertain exactly how long vaccination-induced immunity lasts. We sought to evaluate the seroprevalence and intensity of anti-smallpox immunity among representatives of the present Japanese population. The subjects included 876 individuals who were born between 1937 and 1982. Vaccinia virus-specific immunoglobulin G (IgG) levels were measured by enzyme-linked immunosorbent assay (ELISA), and 152 of 876 samples were also tested for the presence of neutralizing antibodies. Of the subjects who were born before 1962, between 1962 and 1968, and between 1969 and 1975, 98.6, 98.6, and 66.0%, respectively, still retained the vaccinia virus-specific IgG with ELISA values for optical density at 405 nm (OD405) of ≥0.10. The corresponding figures for retained IgGs with OD405 values of ≥0.30 were 91.0, 90.3, and 58.2%, respectively. Neutralizing antibodies were also maintained. The sera with OD405 values of ≥0.30 showed 89% sensitivity and a 93% positive predictive value for detection of neutralizing antibodies (≥4). Thus, approximately 80% of persons born before 1969 and 50% of those born between 1969 and 1975 were also found to have maintained neutralizing antibodies against smallpox. A considerable proportion of the previous vaccinated individuals still retain significant levels of antiviral immunity. This long-lasting immunity may provide some protective benefits in the case of reemergence of smallpox, and the disease may not spread as widely and fatally as generally expected.

scholarly journals Neutralization Assay Using a Modified Vaccinia Virus Ankara Vector Expressing the Green Fluorescent Protein Is a High-Throughput Method To Monitor the Humoral Immune Response against Vaccinia Virus

2004 ◽  
Vol 11 (2) ◽  
pp. 406-410 ◽  
Author(s):  
Antonio Cosma ◽  
Silja Bühler ◽  
Rashmi Nagaraj ◽  
Caroline Staib ◽  
Anna-Lena Hammarin ◽  
...  
Keyword(s):  
Immune Response ◽  
Green Fluorescent Protein ◽  
Vaccinia Virus ◽  
High Throughput ◽  
Neutralizing Antibodies ◽  
Fluorescent Protein ◽  
Safety Concern ◽  
Neutralization Assay ◽  
Modified Vaccinia Virus Ankara ◽  
Green Fluorescent

ABSTRACT Vaccination against smallpox is again considered in order to face a possible bioterrorist threat, but the nature and the level of the immune response needed to protect a person from smallpox after vaccination are not totally understood. Therefore, simple, rapid, and accurate assays to evaluate the immune response to vaccinia virus need to be developed. Neutralization assays are usually considered good predictors of vaccine efficacy and more informative with regard to protection than binding assays. Currently, the presence of neutralizing antibodies to vaccinia virus is measured using a plaque reduction neutralization test, but this method is time-consuming and labor-intensive and has a subjective readout. Here, we describe an innovative neutralization assay based on a modified vaccinia virus Ankara (MVA) vector expressing the green fluorescent protein (MVA-gfp). This MVA-gfp neutralization assay is rapid and sensitive and has a high-throughput potential. Thus, it is suitable to monitor the immune response and eventually the efficacy of a large campaign of vaccination against smallpox and to study the vector-specific immune response in clinical trials that use genetically engineered vaccinia viruses. Most importantly, application of the highly attenuated MVA eliminates the safety concern in using the replication-competent vaccinia virus in the standard clinical laboratory.

Low Immunogenicity to Romiplostim in Clinical Studies with ITP Subjects.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3425-3425 ◽  
Author(s):  
Vibha Jawa ◽  
Martha Hokom ◽  
Jenny Hu ◽  
Yao Zhuang ◽  
Dietmar Berger ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Neutralizing Antibodies ◽  
Single Chain ◽  
Serum Samples ◽  
Binding Domains ◽  
C Terminus ◽  
Before And After ◽  
Immunogenicity Assessment ◽  
Covalently Linked

Abstract Romiplostim, a member of the thrombopoietin (TPO) mimetic class, is an Fc-peptide fusion protein (peptibody) that activates intracellular transcriptional pathways leading to increased platelet production via the TPO receptor (also known as cMpl). The peptibody molecule contains two identical single-chain subunits each consisting of human immunoglobulin IgG1 Fc domain, covalently linked at the C-terminus to a peptide containing two TPO receptor-binding domains. Due to the general concern regarding the immunogenic potential for all therapeutic proteins and the specific concern for monitoring antibodies capable of neutralizing thrombopoietin (TPO), an extensive immunogenicity assessment program was developed to support romiplostim. Romiplostim has been engineered to have no amino acid sequence homology to endogenous TPO. A low theoretical risk of developing conformational antibodies that cross-react against TPO exists. This risk was addressed by using an immunogenicity assessment strategy that relied upon a surface plasmon resonance based biosensor immunoassay using the Biacore 3000 capable of simultaneously monitoring antibodies that bind to romiplostim, TPO, or the active peptide portion of romiplostim (TMP). Samples that tested positive for binding antibodies in the Biacore immunoassay were then tested in the definitive functional biological assay to identify any antibodies capable of neutralizing the biological effect of romiplostim or TPO. Serum samples from 236 actively treated subjects were obtained both before and after exposure to romiplostim and were tested for romiplostim and TPO antibodies. In baseline samples, seventeen subjects (7.1%) tested romiplostim antibody positive and 12 subjects (5.1%) tested TPO antibody positive for pre-existing binding antibodies. After romiplostim exposure, twenty-five out of 236 (10.5%) subjects with ITP developed binding antibodies against romiplostim (inclusive of antibodies to both peptide and the whole molecule) and 12 out of 236 (5.1%) subjects with ITP developed binding antibodies against TPO. The antibodies that developed against romiplostim did not cross react with TPO and the antibodies that developed against TPO did not cross react with romiplostim. The incidence of anti-romiplostim neutralizing antibodies among 236 subjects with ITP who were treated with romiplostim across 10 clinical studies was 0.4% (1 out of 236). No cases of anti-TPO neutralizing antibodies were detected in romiplostim treated samples. In conclusion, after thorough immunogenicity assessment of all subjects treated with romiplostim using sensitive methods to detect binding and neutralizing antibodies, only one subject was found positive for the presence of antibodies capable of neutralizing romiplostim that was negative at the time of follow up 4 months later. As expected, none of the subjects treated were positive for antibodies capable of neutralizing TPO. No clinical sequelae were observed in association to the presence of antibodies.

Singularities of haemorrhagic syndrome in children with native and acquired deficiencies of von Willebrand factor

2013 ◽  
Vol 4 (1) ◽  
pp. 78-85
Author(s):  
Kseniya Ivanovna Pshenichnaya ◽  
Yegor Viktorovich Lyugayev ◽  
Olga Georgiyevna Golovina
Keyword(s):  
Clinical Manifestation ◽  
Von Willebrand Factor ◽  
Clinical Studies ◽  
Clinical Manifestations ◽  
Underlying Disease ◽  
Von Willebrand Disease ◽  
Acquired Von Willebrand Syndrome ◽  
Different Types ◽  
Von Willebrand ◽  
Willebrand Factor

Deficiencies of content in blood and activity of von Willebrand factor can be inborn or acquired with diseases of different nature. Acquired deficiencies of von Willebrand factor or acquired von Willebrand syndrome in children have been described in several clinical studies. This research paper contains data on clinical manifestation and dynamics of haemorrhagic syndrome in 30 children between 13 months and 18 years of age with acquired von Willebrand factor, suffering from different types of pathology. Similarly, clinical manifestations and dynamics of angiostaxis have been studied in 33 children with von Willebrand disease. It has been determined that clinical manifestations of microcirculatory angiostaxis are the same for children from both groups; however, children with acquired von Willebrand syndrome showed dominating limited numbers of haemorrhagical symptoms that were shorter in duration and less intense. Besides, hematomic component of haemorrhagic syndrome was absent. Eventually, accompanied by positive dynamic of the underlying disease, relapses of haemorrhagic syndrome cease, which does not happen in case of the patients with von Willebrand disease.

scholarly journals Conformational States of a Soluble, Uncleaved HIV-1 Envelope Trimer

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Yuhang Liu ◽  
Junhua Pan ◽  
Yongfei Cai ◽  
Nikolaus Grigorieff ◽  
Stephen C. Harrison ◽  
...  
Keyword(s):  
Viral Entry ◽  
Clinical Studies ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Recombinant Form ◽  
Soluble Form ◽  
Compact Structure ◽  
Antigenic Properties ◽  
Hiv 1 ◽  
Gp140 Trimer

ABSTRACT The HIV-1 envelope spike [Env; trimeric (gp160)3 cleaved to (gp120/gp41)3] induces membrane fusion, leading to viral entry. It is also the viral component targeted by neutralizing antibodies. Vaccine development requires production, in quantities suitable for clinical studies, of a recombinant form that resembles functional Env. HIV-1 gp140 trimers—the uncleaved ectodomains of (gp160)3—from a few selected viral isolates adopt a compact conformation with many antigenic properties of native Env spikes. One is currently being evaluated in a clinical trial. We report here low-resolution (20 Å) electron cryomicroscopy (cryoEM) structures of this gp140 trimer, which adopts two principal conformations, one closed and the other slightly open. The former is indistinguishable at this resolution from those adopted by a stabilized, cleaved trimer (SOSIP) or by a membrane-bound Env trimer with a truncated cytoplasmic tail (EnvΔCT). The latter conformation is closer to a partially open Env trimer than to the fully open conformation induced by CD4. These results show that a stable, uncleaved HIV-1 gp140 trimer has a compact structure close to that of native Env. IMPORTANCE Development of any HIV vaccine with a protein component (for either priming or boosting) requires production of a recombinant form to mimic the trimeric, functional HIV-1 envelope spike in quantities suitable for clinical studies. Our understanding of the envelope structure has depended in part on a cleaved, soluble trimer, known as SOSIP.664, stabilized by several modifications, including an engineered disulfide. This construct, which is difficult to produce in large quantities, has yet to induce better antibody responses than those to other envelope-based immunogens, even in animal models. The uncleaved ectodomain of the envelope protein, called gp140, has also been made as a soluble form to mimic the native Env present on the virion surface. Most HIV-1 gp140 preparations are not stable, however, and have an inhomogeneous conformation. The results presented here show that gp140 preparations from suitable isolates can adopt a compact, native-like structure, supporting its use as a vaccine candidate.

scholarly journals Potent and Broadly Reactive HIV-2 Neutralizing Antibodies Elicited by a Vaccinia Virus Vector Prime-C2V3C3 Polypeptide Boost Immunization Strategy

2010 ◽  
Vol 84 (23) ◽  
pp. 12429-12436 ◽  
Author(s):  
José Maria Marcelino ◽  
Pedro Borrego ◽  
Cheila Rocha ◽  
Helena Barroso ◽  
Alexandre Quintas ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Neutralizing Antibodies ◽  
Virus Vector ◽  
Recombinant Polypeptide ◽  
Immunization Strategy ◽  
Loop Sequence ◽  
Immunodeficiency Virus ◽  
Boost Immunization ◽  
Vaccinia Virus Vector

ABSTRACT Human immunodeficiency virus type 2 (HIV-2) infection affects about 1 to 2 million individuals, the majority living in West Africa, Europe, and India. As for HIV-1, new strategies for the prevention of HIV-2 infection are needed. Our aim was to produce new vaccine immunogens that elicit the production of broadly reactive HIV-2 neutralizing antibodies (NAbs). Native and truncated envelope proteins from the reference HIV-2ALI isolate were expressed in vaccinia virus or in bacteria. This source isolate was used due to its unique phenotype combining CD4 independence and CCR5 usage. NAbs were not elicited in BALB/c mice by single immunization with a truncated and fully glycosylated envelope gp125 (gp125t) or a recombinant polypeptide comprising the C2, V3, and C3 envelope regions (rpC2-C3). A strong and broad NAb response was, however, elicited in mice primed with gp125t expressed in vaccinia virus and boosted with rpC2-C3. Serum from these animals potently neutralized (median 50% neutralizing titer, 3,200) six of six highly divergent primary HIV-2 isolates. Coreceptor usage and the V3 sequence of NAb-sensitive isolates were similar to that of the vaccinating immunogen (HIV-2ALI). In contrast, NAbs were not reactive on three X4 isolates that displayed major changes in V3 loop sequence and structure. Collectively, our findings demonstrate that broadly reactive HIV-2 NAbs can be elicited by using a vaccinia virus vector-prime/rpC2-C3-boost immunization strategy and suggest a potential relationship between escape to neutralization and cell tropism.

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