scholarly journals Preclinical studies of immunogenity, protectivity, and safety of the combined vector vaccine for prevention of the middle east respiratory syndrome

Acta Naturae ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 114-123
Author(s):  
Inna V. Dolzhikova ◽  
D. M. Grousova ◽  
O. V. Zubkova ◽  
A. I. Tukhvatulin ◽  
A. V. Kovyrshina ◽  
...  
Keyword(s):  
Immune Response ◽  
Middle East ◽  
Mortality Rate ◽  
Receptor Gene ◽  
Human Adenovirus ◽  
T Cell Response ◽  
Middle East Respiratory Syndrome ◽  
Vector Vaccine ◽  
Humoral Immune ◽  
Cellular Immune

The Middle East Respiratory Syndrome (MERS) is an acute inflammatory disease of the respiratory system caused by the MERS-CoV coronavirus. The mortality rate for MERS is about 34.5%. Due to its high mortality rate, the lack of therapeutic and prophylactic agents, and the continuing threat of the spread of MERS beyond its current confines, developing a vaccine is a pressing task, because vaccination would help limit the spread of MERS and reduce its death toll. We have developed a combined vector vaccine for the prevention of MERS based on recombinant human adenovirus serotypes 26 and 5. Studies of its immunogenicity have shown that vaccination of animals (mice and primates) induces a robust humoral immune response that lasts for at least six months. Studies of the cellular immune response in mice after vaccination showed the emergence of a specific CD4+ and CD8+ T cell response. A study of the vaccine protectivity conducted in a model of transgenic mice carrying the human DPP4 receptor gene showed that our vaccination protected 100% of the animals from the lethal infection caused by the MERS-CoV virus (MERS-CoV EMC/2012, 100LD50 per mouse). Studies of the safety and tolerability of the developed vaccine in rodents, rabbits, and primates showed a good safety profile and tolerance in animals; they revealed no contraindications for clinical testing.

scholarly journals Immunogenicity of Different Forms of Middle East Respiratory Syndrome S Glycoprotein

Acta Naturae ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 38-47 ◽  
Author(s):  
T. A. Ozharovskaia ◽  
O. V. Zubkova ◽  
I. V. Dolzhikova ◽  
A. S. Gromova ◽  
D. M. Grousova ◽  
...  
Keyword(s):  
Immune Response ◽  
Middle East ◽  
Neutralizing Antibodies ◽  
Transmembrane Domain ◽  
Middle East Respiratory Syndrome ◽  
Full Length ◽  
Acute Lower Respiratory Infection ◽  
Th2 Response ◽  
Humoral Immune ◽  
Immunodominant Antigen

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreaks. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~35.5%. Currently, there are no registered vaccines or means of therapeutic protection against MERS in the world. The MERS-CoV S glycoprotein plays the most important role in the viral life cycle (virus internalization). The S protein is an immunodominant antigen and the main target for neutralizing antibodies. In the present study, the immunogenicities of five different forms of the MERS-CoV S glycoprotein were compared: the full-length S glycoprotein, the full-length S glycoprotein with the transmembrane domain of the G glycoprotein of VSV (S-G), the receptor-binding domain (RBD) of the S glycoprotein, the membrane-fused RBD (the RBD fused with the transmembrane domain of the VSV G glycoprotein (RBD-G)), and the RBD fused with Fc of human IgG1 (RBD-Fc). Recombinant vectors based on human adenoviruses type 5 (rAd5) were used as delivery vehicles. Vaccination with all of the developed rAd5 vectors elicited a balanced Th1/Th2 response in mice. The most robust humoral immune response was induced after the animal had been vaccinated with the membrane-fused RBD (rAd5-RBD-G). Only immunization with membrane forms of the glycoprotein (rAd5-S, rAd5-S-G, and rAd5-RBD-G) elicited neutralizing antibodies among all vaccinated animals. The most significant cellular immune response was induced after vaccination of the animals with the full-length S (rAd5-S). These investigations suggest that the full-length S and the membrane form of the RBD (RBD-G) are the most promising vaccine candidates among all the studied forms of S glycoprotein.

scholarly journals Origins and pathogenesis of Middle East respiratory syndrome-associated coronavirus: recent advances

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1628 ◽  
Author(s):  
Stephen A. Goldstein ◽  
Susan R. Weiss
Keyword(s):  
Immune Response ◽  
Middle East ◽  
Animal Models ◽  
Case Fatality ◽  
Innate Immune ◽  
Middle East Respiratory Syndrome ◽  
Live Virus ◽  
Novel Proteins ◽  
Significant Research ◽  
African Bats

Middle East respiratory syndrome-associated coronavirus (MERS-CoV) has been a significant research focus since its discovery in 2012. Since 2012, 2,040 cases and 712 deaths have been recorded (as of August 11, 2017), representing a strikingly high case fatality rate of 36%. Over the last several years, MERS-CoV research has progressed in several parallel and complementary directions. This review will focus on three particular areas: the origins and evolution of MERS-CoV, the challenges and achievements in the development of MERS-CoV animal models, and our understanding of how novel proteins unique to MERS-CoV counter the host immune response. The origins of MERS-CoV, likely in African bats, are increasingly clear, although important questions remain about the establishment of dromedary camels as a reservoir seeding human outbreaks. Likewise, there have been important advances in the development of animal models, and both non-human primate and mouse models that seem to recapitulate human disease are now available. How MERS-CoV evades and inhibits the host innate immune response remains less clear. Although several studies have identified MERS-CoV proteins as innate immune antagonists, little of this work has been conducted using live virus under conditions of actual infection, but rather with ectopically expressed proteins. Accordingly, considerable space remains for major contributions to understanding unique ways in which MERS-CoV interacts with and modulates the host response. Collectively, these areas have seen significant advances over the last several years but continue to offer exciting opportunities for discovery.

scholarly journals EFFECT OF BACILLUS OF CALMETTE-GUÉRIN, AVRIDINE AND Propionibacterium acnes AS IMMUNOMODULATORS ON RABIES IN MICE

1999 ◽  
Vol 41 (2) ◽  
pp. 107-114 ◽  
Author(s):  
J. MEGID ◽  
M.T.S. PERAÇOLI ◽  
P.R. CURI ◽  
C.R. ZANETTI ◽  
W.H. CABRERA ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Cellular Immune Response ◽  
Propionibacterium Acnes ◽  
Inoculation Test ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cellular Immune

The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment. Lower levels of interferon-<FONT FACE="Symbol">g</font> (IFN-<FONT FACE="Symbol">g</font>) were found in infected mice. The intra-pad inoculation test (IPI) was not effective to detect cellular immune response, contrary to the results found in MIF reaction. The survival of mice did not present correlation with the levels of antirabies serum neutralizing (SN) antibodies titers, IFN-<FONT FACE="Symbol">g</font> concentration and MIF response.

scholarly journals Vaccination of Mice with a Novel Trypsin from Trichinella spiralis Elicits the Immune Protection against Larval Challenge

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 437 ◽  
Author(s):  
Yao Zhang ◽  
Jie Zeng ◽  
Yan Yan Song ◽  
Shao Rong Long ◽  
Ruo Dan Liu ◽  
...  
Keyword(s):  
Immune Response ◽  
Trichinella Spiralis ◽  
Biological Properties ◽  
Target Antigen ◽  
Immune Protection ◽  
Humoral Immune ◽  
Meat Safety ◽  
Muscle Larvae ◽  
Candidate Target ◽  
Cellular Immune

Trichinella spiralis is a major foodborne parasite and has a serious threat to meat safety. Development of anti-Trichinella vaccines is prospective to eliminate Trichinella infection in food animal. The aim of this study was to assess the biological properties of a novel T. spiralis trypsin (TsT) and its elicited immune protection against larval challenge. The cDNA sequence of TsT gene was cloned and expressed. Western blotting showed rTsT was identified by infection serum and anti-TsT serum. RT-PCR results revealed that TsT gene was transcribed at diverse T. spiralis lifecycle stages. The IIFT results showed that natural TsT was principally expressed at epicuticle of 5-6 day adult worms, indicating that TsT is a worm somatic antigen and adult-stage specific surface antigen. Vaccination of mice with rTsT triggered an evident humoral immune response (high levels of serum IgG, IgG1/IgG2a, and enteral sIgA), and it also induced the systemic and enteral local cellular immune response, demonstrated by an significantly elevation of cytokines IFN-γ and IL-4. The mice vaccinated with rTsT exhibited a 33.17% reduction of enteral adult worms and a 37.80% reduction of muscle larvae after larval challenge. The results showed that TsT might be considered as a candidate target antigen for anti-T. spiralis vaccines.

scholarly journals Humoral and Cellular Immune Response to RNA Immunization with Flavivirus Replicons Derived from Tick-Borne Encephalitis Virus

2005 ◽  
Vol 79 (24) ◽  
pp. 15107-15113 ◽  
Author(s):  
Judith H. Aberle ◽  
Stephan W. Aberle ◽  
Regina M. Kofler ◽  
Christian W. Mandl
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Cell Response ◽  
Cellular Immune Response ◽  
T Cell Response ◽  
The Self ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Cellular Immune ◽  
Rna Vaccine

ABSTRACT A new vaccination principle against flaviviruses, based on a tick-borne encephalitis virus (TBEV) self-replicating noninfectious RNA vaccine that produces subviral particles, has recently been introduced (R. M. Kofler, J. H. Aberle, S. W. Aberle, S. L. Allison, F. X. Heinz, and C. W. Mandl, Proc. Natl. Acad. Sci. USA 7:1951-1956, 2004). In this study, we evaluated the potential of the self-replicating RNA vaccine in mice in comparison to those of live, attenuated vaccines and a formalin-inactivated whole-virus vaccine (ImmunInject). For this purpose, mice were immunized using gene gun-mediated application of the RNA vaccine and tested for CD8+ T-cell responses, long-term duration, neutralizing capacity, and isotype profile of specific antibodies and protection against lethal virus challenge. We demonstrate that the self-replicating RNA vaccine induced a broad-based, humoral and cellular (Th1 and CD8+ T-cell response) immune response comparable to that induced by live vaccines and that it protected mice from challenge. Even a single immunization with 1 μg of the replicon induced a long-lasting antibody response, characterized by high neutralizing antibody titers, which were sustained for at least 1 year. Nevertheless, it was possible to boost this response further by a second injection with the RNA vaccine, even in the presence of a concomitant CD8+ T-cell response. In this way it was possible to induce a balanced humoral and cellular immune response, similar to infection-induced immunity but without the safety hazards of infectious agents. The results also demonstrate the value of TBEV replicon RNA for inducing protective long-lasting antiviral responses.

scholarly journals Engineering a Replication-Competent, Propagation-Defective Middle East Respiratory Syndrome Coronavirus as a Vaccine Candidate

mBio ◽  
2013 ◽  
Vol 4 (5) ◽  
Author(s):  
Fernando Almazán ◽  
Marta L. DeDiego ◽  
Isabel Sola ◽  
Sonia Zuñiga ◽  
Jose L. Nieto-Torres ◽  
...  
Keyword(s):  
Middle East ◽  
Mortality Rate ◽  
Bacterial Artificial Chromosome ◽  
Cdna Clone ◽  
Reverse Genetics ◽  
Infectious Virus ◽  
Vaccine Candidate ◽  
Artificial Chromosome ◽  
Middle East Respiratory Syndrome ◽  
E Protein

ABSTRACTMiddle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus infecting humans that is associated with acute pneumonia, occasional renal failure, and a high mortality rate and is considered a threat to public health. The construction of a full-length infectious cDNA clone of the MERS-CoV genome in a bacterial artificial chromosome is reported here, providing a reverse genetics system to study the molecular biology of the virus and to develop attenuated viruses as vaccine candidates. Following transfection with the cDNA clone, infectious virus was rescued in both Vero A66 and Huh-7 cells. Recombinant MERS-CoVs (rMERS-CoVs) lacking the accessory genes 3, 4a, 4b, and 5 were successfully rescued from cDNA clones with these genes deleted. The mutant viruses presented growth kinetics similar to those of the wild-type virus, indicating that accessory genes were not essential for MERS-CoV replication in cell cultures. In contrast, an engineered mutant virus lacking the structural E protein (rMERS-CoV-ΔE) was not successfully rescued, since viral infectivity was lost at early passages. Interestingly, the rMERS-CoV-ΔE genome replicated after cDNA clone was transfected into cells. The infectious virus was rescued and propagated in cells expressing the E protein intrans, indicating that this virus was replication competent and propagation defective. Therefore, the rMERS-CoV-ΔE mutant virus is potentially a safe and promising vaccine candidate to prevent MERS-CoV infection.IMPORTANCESince the emergence of MERS-CoV in the Arabian Peninsula during the summer of 2012, it has already spread to 10 different countries, infecting around 94 persons and showing a mortality rate higher than 50%. This article describes the development of the first reverse genetics system for MERS-CoV, based on the construction of an infectious cDNA clone inserted into a bacterial artificial chromosome. Using this system, a collection of rMERS-CoV deletion mutants has been generated. Interestingly, one of the mutants with the E gene deleted was a replication-competent, propagation-defective virus that could only be grown in the laboratory by providing E protein intrans, whereas it would only survive a single virus infection cyclein vivo. This virus constitutes a vaccine candidate that may represent a balance between safety and efficacy for the induction of mucosal immunity, which is needed to prevent MERS-CoV infection.

scholarly journals Pathological changes inducing by S.aureus in immunodeficiency mice immunized with Soluble Culture Filtrate S.aureus Antigens (SCFAgs)

2013 ◽  
Vol 12 (1) ◽  
pp. 71
Author(s):  
H. H. K. AL-Byattee
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Culture Filtrate ◽  
Post Inoculation ◽  
Bacterial Isolation ◽  
Positive Group ◽  
Treatment Groups ◽  
Humoral Immune ◽  
Sterile Normal Saline ◽  
Cellular Immune

In order to determine the influence of Soluble Culture Filtrate S.aureus Antigens (SCFAgs)on S.aureus infection in Mitomicin c immunosupression mice, seventy four white mice, both sex,7-8 weeks age were divided randomly into five groups.1st group(n=16 ) was immunized with 0.4ml of S.aureus CFSAgs (concentration of protein( 4.2mg/ml) ,i/p two doses, 2 weeks intervals. 2nd group(n=16) was injected with mitomycine C ,(1mg/kg B.W) I/p three time /week for 4 weeks. 3ed group (n=16) was immunized with CFSAgs as 1st group and treated with mitomycin as 2nd group. 4th group(n=10) was inoculated with (0.4ml) I/P with1X109 CFU/ML of viable virulent. S.aureus and was served as control positive group. 5th group (n=16) was inoculated with 0.5ml sterile normal saline. Cellular and humoral immune response were recorded at 28-30 day post immunization, skin test and passive heam agglutination test respectively, then all animals of immunized and treatment groups were challenge with S,aureus as control positive group. The results explained that animals treatment with MMC were died during (18) hrs post inoculation with virulent viable S.aureus with very heavy bacterial isolation, animal of control positive group were died at( 24)hrs post infection with heavy bacterial isolation The results revealed that immunization with CFSAgs elicited both humoral and cellular immune responses, the level values of both arms of immune response were lower animal treatment with MMC, Severe pathological lesions were seen in examined organs of control positive group but these lesions are more extensive in animal treatment with MMC. The main lesions in examined organs of these animals are suppurative inflammation ,congestion ,apoptosis and necrosis.. We conclusion that MMC induce immunosuppression condition and immunization with CFSAgs can improve the immune responses in the animals that are suffering from immunosuppression.

scholarly journals Preserved T-cell Response in anti-CD20 Treated Multiple Sclerosis Patients Following SARS-CoV-2 Vaccination

2021 ◽  
Author(s):  
Simon Faissner ◽  
Neele Heitmann ◽  
Ricarda Rohling ◽  
Ulas Ceylan ◽  
Marielena Bongert ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Immune Response ◽  
T Cell ◽  
B Cell ◽  
T Cell Response ◽  
Th2 Cells ◽  
Multiple Sclerosis Patients ◽  
Cellular Immune ◽  
Cell Repopulation

Abstract The SARS-CoV-2 pandemic has tremendous implications for the management of patients with autoimmune conditions such as multiple sclerosis (MS) under immune therapies targeting CD20+ B cells (aCD20). We here investigated humoral and cellular immune responses, including neutralization against SARS-CoV-2 WT and delta variant and T cell responses of aCD20-treated MS patients following SARS-CoV-2 vaccination compared to healthy controls. aCD20-treated MS patients had lower anti-SARS-CoV-2-Spike titers, which correlated with B-cell repopulation. Sera of aCD20 treated patients had reduced capacity to neutralize WT and delta pseudoviruses in vitro. On the contrary, aCD20 treated patients elicited higher frequencies of CD3+ T cells, Th1 cells, Th2 cells, Tc1 cells and CD8+IFN-γ+IL-2+ cells. In summary, aCD20 treated patients have a reduced humoral immune response, depending on B cell repopulation, in accordance with a shift of cellular immune response to a stronger Th1, Th2 and Tc1 phenotype, suggesting strong cellular protection against SARS-CoV-2.

scholarly journals Enhancement of the Local CD8+ T-Cellular Immune Response to Mycobacterium tuberculosis in BCG-Primed Mice after Intranasal Administration of Influenza Vector Vaccine Carrying TB10.4 and HspX Antigens

Vaccines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1273
Author(s):  
Kirill Vasilyev ◽  
Anna-Polina Shurygina ◽  
Natalia Zabolotnykh ◽  
Mariia Sergeeva ◽  
Ekaterina Romanovskaya-Romanko ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Cellular Immune Response ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Adaptive Immune Response ◽  
Reading Frame ◽  
Vector Vaccine ◽  
Specific Effector ◽  
Cellular Immune

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.

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