scholarly journals Immune responses in mice induced by multi-epitope DNA vaccine and protein vaccine of Crimean-Congo Hemorrhagic Fever Virus

2019 ◽  
Author(s):  
Meilipaiti Yusufu ◽  
Alai Shalitanati ◽  
Huan Yu ◽  
Abulimiti Moming ◽  
Yijie Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Hemorrhagic Fever ◽  
Control Group ◽  
Protein Vaccine ◽  
Crimean Congo Hemorrhagic Fever ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Significant Difference ◽  
Double Copy

AbstractCrimean-Congo Hemorrhagic Fever (CCHF), caused by the CCHF virus (CCHFV), is a severe tick borne zoonosis widely distributed in over 30 countries and regions. Currently, there is no licensed vaccine available for CCHF in China. To evaluate the cellular and humoral immune responses induced by multi-epitope DNA and protein vaccine of CCHF in BALB/c mice, a multi-epitope gene (MEPX) segment with tandem including six highly conservative and immunedominant B cell epitopes was designed based on the analysis of hydrophilicity and antigenic determinant sites in amino acid sequences of nucleoprotein and glycoprotein from CCHFV strain YL04057. The single and double-copy multi-epitope gene (MEPX and MEPX2) were respectively cloned into the eukaryotic expression vector pVAX I to construct the recombinant (r) plasmid pVAX-MEPX and pVAX-MEPX2 as DNA vaccines. The results of immunofluorescence in vitro showed that the pVAX-MEPX and pVAX-MEPX2 could be expressed in 293T cells. The recombinant prokaryotic plasmid pET-32a-MEPX and pET-32a-MEPX2 constructed previously were transformed them into E. coli BL21 (DE3), and recombinant multi-epitope proteins (rMEPX and rMEPX2) were obtained and purificated by Nickel affinity chromatography. Western blot results showed that rMEPX and rMEPX2 had good antigenicity. BALB/c mice were immunized with DNA vaccine alone, protein vaccine alone, and DNA prime followed by recombinant protein boost immunization strategy, respectively. After three immunizations, MTT assay, cytokine content assay, and ELISA assay for antibody titers were used to evaluate the immune response. The proliferation of mouse specific T lymphocytes in the enhanced by pVAX-MEPX2 combined with rMEPX2 boosting group was significant, and the expression levels of serum IFN-γ and IL-4 in mice were as high as 118.67 pg/mL and 135.33 pg/mL with significant difference compared to the control group (p<0.01), and serum antibody titer could reach up to 4.1×105. Double-copy multi-epitope vaccines groups (pVAX-MEPX2+ rMEPX2) generated better cellular and humoral immune responses by DNA prime-protein vaccine boost combinatorial immunization. This result could lay the foundation for the development of CCHFV multi-epitope vaccine candidates.

scholarly journals Effect of nabumetone on humoral immune responses in mice

2020 ◽  
Vol 72 (3) ◽  
pp. 915-920
Author(s):  
Khalid Naveed ◽  
Aqeel Javeed ◽  
Muhammad Ashraf ◽  
Amjad Riaz ◽  
Aamir Ghafoor ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Immune Response ◽  
Immune Responses ◽  
Plaque Formation ◽  
Control Group ◽  
Treatment Groups ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Significant Difference ◽  
Mortality Ratio

ABSTRACT Nabumetone is used to reduce the pain and inflammation in rheumatoid arthritis. In the current study, immunomodulatory effect of Nabumetone is investigated in mice. The control group was administered normal saline orally as placebo. Nabumetone was administered orally via gavage in two treatment groups at 14mg/kg.b.w. doses and 28mg/kgb.w., respectively. Haemagglutination (HA) assay, Jerne hemolytic plaque and mice lethality assays were applied. In HA assay, the titer was significantly decreased in Nabumetone treatment groups (P< 0.001). In Jerne hemolytic plaque formation assay, there was a significant reduction (P< 0.001) in number of plaques in Nabumetone treated groups when compared with control. In mice lethality assay, there was a significant difference in mortality ratio of mice in control and Nabumetone treated groups (P< 0.001). Therefore, it is concluded that Nabumetone suppresses the humoral immune response in mice.

scholarly journals Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Cynthia Machín ◽  
Yolanda Corripio-Miyar ◽  
Julia N. Hernández ◽  
Tara Pérez-Hernández ◽  
Adam D. Hayward ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Anthelmintic Resistance ◽  
Gastrointestinal Nematodes ◽  
Control Group ◽  
Sheep Breeds ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Teladorsagia Circumcincta

AbstractDue to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.

scholarly journals Targeting with Bovine CD154 Enhances Humoral Immune Responses Induced by a DNA Vaccine in Sheep

2003 ◽  
Vol 170 (2) ◽  
pp. 989-996 ◽  
Author(s):  
Sharmila Manoj ◽  
Philip J. Griebel ◽  
Lorne A. Babiuk ◽  
Sylvia van Drunen Littel-van den Hurk
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses

scholarly journals Immunization with DNA Plasmids Coding for Crimean-Congo Hemorrhagic Fever Virus Capsid and Envelope Proteins and/or Virus-Like Particles Induces Protection and Survival in Challenged Mice

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Jorma Hinkula ◽  
Stéphanie Devignot ◽  
Sara Åkerström ◽  
Helen Karlberg ◽  
Eva Wattrang ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Neutralizing Antibodies ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Vaccine Candidates ◽  
Th1 Response ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus

ABSTRACT Crimean-Congo hemorrhagic fever virus (CCHFV) is a bunyavirus causing severe hemorrhagic fever disease in humans, with high mortality rates. The requirement of a high-containment laboratory and the lack of an animal model hampered the study of the immune response and protection of vaccine candidates. Using the recently developed interferon alpha receptor knockout (IFNAR−/−) mouse model, which replicates human disease, we investigated the immunogenicity and protection of two novel CCHFV vaccine candidates: a DNA vaccine encoding a ubiquitin-linked version of CCHFV Gc, Gn, and N and one using transcriptionally competent virus-like particles (tc-VLPs). In contrast to most studies that focus on neutralizing antibodies, we measured both humoral and cellular immune responses. We demonstrated a clear and 100% efficient preventive immunity against lethal CCHFV challenge with the DNA vaccine. Interestingly, there was no correlation with the neutralizing antibody titers alone, which were higher in the tc-VLP-vaccinated mice. However, the animals with a lower neutralizing titer, but a dominant cell-mediated Th1 response and a balanced Th2 response, resisted the CCHFV challenge. Moreover, we found that in challenged mice with a Th1 response (immunized by DNA/DNA and boosted by tc-VLPs), the immune response changed to Th2 at day 9 postchallenge. In addition, we were able to identify new linear B-cell epitope regions that are highly conserved between CCHFV strains. Altogether, our results suggest that a predominantly Th1-type immune response provides the most efficient protective immunity against CCHFV challenge. However, we cannot exclude the importance of the neutralizing antibodies as the surviving immunized mice exhibited substantial amounts of them. IMPORTANCE Crimean-Congo hemorrhagic fever virus (CCHFV) is responsible for hemorrhagic diseases in humans, with a high mortality rate. There is no FDA-approved vaccine, and there are still gaps in our knowledge of the immune responses to infection. The recently developed mouse models mimic human CCHF disease and are useful to study the immunogenicity and the protection by vaccine candidates. Our study shows that mice vaccinated with a specific DNA vaccine were fully protected. Importantly, we show that neutralizing antibodies are not sufficient for protection against CCHFV challenge but that an extra Th1-specific cellular response is required. Moreover, we describe the identification of five conserved B-cell epitopes, of which only one was previously known, that could be of great importance for the development of diagnostics tools and the improvement of vaccine candidates.

Safety, tolerability and humoral immune responses after intramuscular administration of a malaria DNA vaccine to healthy adult volunteers

Vaccine ◽  
2000 ◽  
Vol 18 (18) ◽  
pp. 1893-1901 ◽  
Author(s):  
Thong P. Le ◽  
Kevin M. Coonan ◽  
Richard C. Hedstrom ◽  
Yupin Charoenvit ◽  
Martha Sedegah ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Vaccine ◽  
Healthy Adult ◽  
Intramuscular Administration ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Adult Volunteers

scholarly journals Overcoming Immunity to a Viral Vaccine by DNA Priming before Vector Boosting

2003 ◽  
Vol 77 (1) ◽  
pp. 799-803 ◽  
Author(s):  
Zhi-yong Yang ◽  
Linda S. Wyatt ◽  
Wing-pui Kong ◽  
Zoe Moodie ◽  
Bernard Moss ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Vectors ◽  
Ebola Virus ◽  
Viral Vector ◽  
Hemorrhagic Fever ◽  
Viral Immunity ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Viral Vaccine ◽  
Humoral Responses

ABSTRACT Replication-defective adenovirus (ADV) and poxvirus vectors have shown potential as vaccines for pathogens such as Ebola or human immunodeficiency virus in nonhuman primates, but prior immunity to the viral vector in humans may limit their clinical efficacy. To overcome this limitation, the effect of prior viral exposure on immune responses to Ebola virus glycoprotein (GP), shown previously to protect against lethal hemorrhagic fever in animals, was studied. Prior exposure to ADV substantially reduced the cellular and humoral immune responses to GP expressed by ADV, while exposure to vaccinia inhibited vaccine-induced cellular but not humoral responses to GP expressed by vaccinia. This inhibition was largely overcome by priming with a DNA expression vector before boosting with the viral vector. Though heterologous viral vectors for priming and boosting can also overcome this effect, the paucity of such clinical viral vectors may limit their use. In summary, it is possible to counteract prior viral immunity by priming with a nonviral, DNA vaccine.

scholarly journals Limited ability of humoral immune responses in control of viremia during infection with SIVsmmD215 strain

Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4250-4261 ◽  
Author(s):  
Thaidra Gaufin ◽  
Rajeev Gautam ◽  
Melissa Kasheta ◽  
Ruy Ribeiro ◽  
Erin Ribka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antibody Production ◽  
Neutralizing Antibody ◽  
Viral Loads ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Significant Difference ◽  
Anti Cd20 ◽  
And Control ◽  
The Impact

AbstractWe investigated the impact of rhesus macaque (RM) B-cell depletion before inoculation with the isolate SIVsmmD215. Seven RMs were treated every 3 weeks with 50 mg/kg of an anti-CD20 antibody (rituximab) starting 7 days before inoculation for 2 (n = 4) and 5 (n = 3) months. Four control animals received no antibody. Three animals were completely depleted of CD20+ B cells, but 4 were only partially depleted of CD20 cells in the LNs and intestine. The decrease in antibody production was consistent with the efficacy of tissue CD20 depletion. Seroconversion and neutralizing antibody production was significantly delayed in animals showing complete tissue CD20 depletion and remained at low titers in all CD20-depleted RMs. Surprisingly, there was no significant difference in acute or chronic viral loads between CD20-depleted and control animal groups. There was a tendency for lower viral set points in CD20-depleted animals. At 6 weeks after inoculation, cellular immune responses were significantly stronger in CD20-depleted animals than in controls. There was no significant difference in survival between CD20-depleted and control animals. Our data suggest that a deficiency of Ab responses did not markedly affect viral replication or disease progression and that they may be compensated by more robust cellular responses.

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