scholarly journals Immunization With a DNA Vaccine Encoding the Toxoplasma gondii’ s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuchao Zhu ◽  
Yanan Xu ◽  
Lu Hong ◽  
Chunxue Zhou ◽  
Jia Chen
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Survival Time ◽  
Protective Efficacy ◽  
Serum Antibody ◽  
Cyst Formation ◽  
Dna Immunization ◽  
Genotype I ◽  
Significant Difference ◽  
Cellular Immune

Toxoplasma gondii, an obligate intracellular protozoan parasite, can cause infect almost all warm-blooded animals and humans. To evaluate the immunogenicity and protective efficacy of T. gondii GRA39 (TgGRA39) in mice by using DNA immunization, we constructed a recombinant eukaryotic plasmid pVAX-TgGRA39. The specific immune responses in immunized mice were analyzed by serum antibody and cytokine measurements, lymphocyte proliferation assays and flow cytometry of T lymphocyte subclasses. Also, protective efficacy against acute and chronic T. gondii infection was assessed by observing the survival time after challenge with the highly virulent T. gondii RH strain (Genotype I) and counting the number of cyst-forming in brain at 4 weeks post-infection with the cyst-forming PRU strain of T. gondii (Genotype II), respectively. Our results showed that DNA immunization with pVAX-GRA39 via intramuscular injection three times, at 2-week intervals could elicit humoral and cellular immune response, indicated by enhanced levels of IgG and IgG2a antibodies (a slightly elevated IgG2a to IgG1 ratio), and increased levels of cytokines IFN-γ, IL-2, IL-12, IL-17A, IL-17F, IL-22 and IL-23 and percentages of CD3+ CD4+ CD8- and CD3+ CD8+ CD4– T cells, in contrast to non-immunized mice. The significant increase in the expression levels of IL-6, TGF-β1, IL-1β, and the transcription factor factors RORγt, RORα, and STAT3 involved in the activation and pathway of Th17 and Tc17 cells, were also observed. However, no significant difference was detected in level of IL-4 and IL-10 (p > 0.05). These effective immune responses had mounted protective immunity against T. gondii infection, with a prolonged survival time (16.80 ± 3.50 days) and reduced cyst numbers (44.5%) in comparison to the control mice. Our data indicated that pVAX-TgGRA39 could induce effective humoral, and Th1-type, Th17, and Tc17 cellular immune responses, and may represent a promising vaccine candidate against both acute and chronic T. gondii infection.

scholarly journals Protective Efficacy of an Inactive Vaccine Based on the LY02 Isolate against AcuteHaemophilus parasuisInfection in Piglets

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Xiao-Hua Li ◽  
Guo-Zhen Zhao ◽  
Long-Xin Qiu ◽  
Ai-Ling Dai ◽  
Wang-Wei Wu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Haemophilus Parasuis ◽  
Fujian Province ◽  
Cellular Immune Responses ◽  
Glässer’S Disease ◽  
Potential Vaccine ◽  
Cellular Immune ◽  
Glasser's Disease

Haemophilus parasuiscan cause Glässer’s disease characterized by fibrinous polyserositis, polyarthritis, and meningitis. The current prevention of Glässer’s disease is mainly based on the inactive vaccines; however, the protective efficacy usually fails in heterogeneous or homologous challenges. Here, the predominant lineage ofH. parasuis(LY02 strain) in Fujian province, China, characterized as serovar 5, was used to evaluate the protective immunity against acuteH. parasuisinfection in piglets after inactivation. Following challenging withH. parasuis,only mild lesions in the pigs immunized with the killed vaccine were observed, whereas the typical symptoms of Glässer’s disease presented in the nonimmunized piglets. A strong IgG immune response was induced by the inactive vaccine. CD4+and CD8+T lymphocyte levels were increased, indicating the potent cellular immune responses were elicited. The significantly high levels of IL-2, IL-4, TGF-β, and IFN-γin sera from pigs immunized with this killed vaccine suggested that the mixed Th1 and Th2 immune responses were induced, associated with the high protection againstH. parasuisinfection compared to the nonimmunized animals. This study indicated that the inactivated LY02 strain ofH. parasuiscould serve as a potential vaccine candidate to prevent the prevalence ofH. parasuisin Fujian province, China.

Tandem antioxidant enzymes confer synergistic protective responses in experimental filariasis

2013 ◽  
Vol 88 (4) ◽  
pp. 402-410 ◽  
Author(s):  
P.R. Prince ◽  
J. Madhumathi ◽  
G. Anugraha ◽  
P.J. Jeyaprita ◽  
M.V.R. Reddy ◽  
...  
Keyword(s):  
Immune Responses ◽  
Redox Regulation ◽  
Protective Efficacy ◽  
Wuchereria Bancrofti ◽  
Parasite Clearance ◽  
Cross Reactivity ◽  
Host Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Helminth Parasites ◽  
Cellular Immune

AbstractHelminth parasites use antioxidant defence strategies for survival during oxidative stress due to free radicals in the host. Accordingly, tissue-dwelling filarial parasites counteract host responses by releasing a number of antioxidants. Targeting these redox regulation proteins together, would facilitate effective parasite clearance. Here, we report the combined effect of protective immune responses trigged by recombinant Wuchereria bancrofti thioredoxin (WbTRX) and thioredoxin peroxidase (WbTPX) in an experimental filarial model. The expression of WbTRX and WbTPX in different stages of the parasite and their cross-reactivity were analysed by enzyme-linked immunosorbent assay (ELISA). The immunogenicity of recombinant proteins and their protective efficacy were studied in animal models when immunized in single or cocktail mode. The antigens showed cross-reactive epitopes and induced high humoral and cellular immune responses in mice. Further, parasite challenge against Brugia malayi L3 larvae in Mastomyscoucha conferred significant protection of 57% and 62% against WbTRX and WbTPX respectively. The efficacy of L3 clearance was significantly higher (71%) (P <  0.001) when the antigens were immunized together, showing a synergistic effect in multiple-mode vaccination. Hence, the study suggests WbTRX and WbTPX to be attractive vaccine candidates when immunized together and provides a tandem block for parasite elimination in the control of lymphatic filariasis.

scholarly journals Enhanced cellular immunity and systemic control of SHIV infection by combined parenteral and mucosal administration of a DNA prime MVA boost vaccine regimen

2004 ◽  
Vol 85 (8) ◽  
pp. 2407-2419 ◽  
Author(s):  
B. Mäkitalo ◽  
P. Lundholm ◽  
J. Hinkula ◽  
C. Nilsson ◽  
K. Karlén ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Protective Efficacy ◽  
Viral Rna ◽  
Post Challenge ◽  
Cellular Immune Responses ◽  
Immunodeficiency Virus ◽  
Cellular Immune ◽  
Hiv 1 ◽  
Rna Levels

The immunogenicity and protective efficacy of a DNA and recombinant modified vaccinia Ankara (MVA) vaccine administered by two different routes were investigated. DNA expressing HIV-1 IIIB env, gag, RT, rev, tat and nef, and MVA expressing HIV-1 IIIB nef, tat and rev and simian immunodeficiency virus (SIV) macJ5 gag/pol and vaccinia HIV-1 env, were used as immunogens. Four cynomolgus macaques received DNA intramuscularly (i.m.) at month 0 and intrarectally (i.r.) and intra-orally (i.o.) at 2 months, followed by MVA i.m. at 4 months and i.r. and i.o. at 8 months. Another group of four monkeys received the same immunogens but only i.m.. Overall, stronger cellular immune responses measured by ELISPOT and T-cell proliferation assay were detected in the group primed i.m. and boosted mucosally. Following homologous intravenous simian-human immunodeficiency virus (SHIV) challenge, one of eight vaccinated animals was completely protected. This monkey, immunized i.m. and i.r.+i.o., exhibited the highest levels of HIV Env, Nef and Tat antibodies, high HIV Tat cytotoxic T-lymphocyte activity and T-lymphocyte proliferative responses to HIV Env. Four weeks post-challenge none of the monkeys immunized i.m. and i.r.+i.o., and only two out of four animals immunized i.m., demonstrated detectable plasma viral RNA levels. In contrast, all eight control animals had demonstrable plasma viral RNA levels 4 weeks post-challenge. Thus, stronger cellular immune responses and reduction of challenge virus burden were demonstrated in animals immunized i.m. as well as mucosally, compared with animals immunized i.m. only. The breadth and magnitude of the induced immune responses correlated with protective efficacy.

scholarly journals Ad26.COV2.S or BNT162b2 Boosting of BNT162b2 Vaccinated Individuals

2021 ◽  
Author(s):  
C. Sabrina Tan ◽  
Ai-ris Y. Collier ◽  
Jinyan Liu ◽  
Jingyou Yu ◽  
Huahua Wan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Efficacy ◽  
Cellular Immune Responses ◽  
Antibody Titers ◽  
Cellular Immune

ABSTRACTPrevious studies have reported that a third dose of the BNT162b2 (Pfizer) COVID-19 vaccine increased antibody titers and protective efficacy. Here we compare humoral and cellular immune responses in 65 individuals who were vaccinated with the BNT162b2 vaccine and were boosted after at least 6 months with either Ad26.COV2.S (Johnson & Johnson; N=41) or BNT162b2 (Pfizer; N=24).

scholarly journals Differential Effects of Prior Exposure to Environmental Mycobacteria on Vaccination with Mycobacterium bovis BCG or a Recombinant BCG Strain Expressing RD1 Antigens

2005 ◽  
Vol 73 (4) ◽  
pp. 2190-2196 ◽  
Author(s):  
Caroline Demangel ◽  
Thierry Garnier ◽  
Ida Rosenkrands ◽  
Stewart T. Cole
Keyword(s):  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Protective Efficacy ◽  
In Silico Analysis ◽  
Inhibitory Effect ◽  
Protective Antigens ◽  
Environmental Mycobacteria ◽  
Cellular Immune ◽  
The Impact ◽  
Recombinant Bcg

ABSTRACT In silico analysis reveals that most protective antigens expressed by the antituberculous vaccine Mycobacterium bovis BCG (BCG) are conserved in M. avium, supporting the hypothesis that exposure to environmental mycobacteria generates cross-reactive immune responses blocking BCG activity. We investigated the impact of sensitization with M. avium, M. scrofulaceum, or M. vaccae on the protective efficacy of a recombinant BCG strain expressing RD1 antigens (BCG::RD1), using a mouse model of experimental tuberculosis (TB). No evidence that the RD1-encoded antigens ESAT-6, CFP-10, and PPE68 were expressed by these environmental strains could be demonstrated by Western blot analysis. Mice sensitized with each of these strains did not prime cellular immune responses cross-reacting with the immunodominant ESAT-6. Importantly, clearance of BCG::RD1 from the lungs and spleens of mice exposed to each of the environmental strains before vaccination was minimal compared to that of BCG. In mice sensitized with M. avium, increased persistence of BCG::RD1 correlated with stronger antimycobacterial gamma interferon responses and enhanced protection against aerosol infection with M. tuberculosis, compared to BCG. In contrast, animals exposed to M. scrofulaceum or M. vaccae prior to vaccination with BCG or BCG::RD1 were better protected against TB than were the unsensitized controls. Our results suggest that the inhibitory effect of environmental mycobacteria on the protective efficacy of BCG depends critically on the extent of cross-recognition of antigens shared with the vaccine. In hosts sensitized with M. avium, potent immunogenicity of ESAT-6 and increased persistence of BCG::RD1 may allow this recombinant vaccine to overcome preexisting antimycobacterial responses.

scholarly journals Cellular Immune Responses to Recombinant Mycobacterium bovis BCG Constructs Expressing Major Antigens of Region of Difference 1 of Mycobacterium tuberculosis

2013 ◽  
Vol 20 (8) ◽  
pp. 1230-1237 ◽  
Author(s):  
Kholoud Shaban ◽  
Hanady A. Amoudy ◽  
Abu S. Mustafa
Keyword(s):  
Immune Responses ◽  
Mycobacterium Bovis ◽  
Protective Efficacy ◽  
Spleen Cells ◽  
T Helper 1 ◽  
Th1 Cell ◽  
Content Type ◽  
Cellular Immune Responses ◽  
Ifn Γ ◽  
Cellular Immune

ABSTRACTBesides being the most widely used vaccine directed against tuberculosis (TB) worldwide,Mycobacterium bovisBCG is also the most controversial vaccine in current use. Its protective efficacy varies widely in different parts of the world. One approach to improving the current BCG vaccine might be to produce recombinant BCG strains that express major antigens encoded by genes that are present in theM. tuberculosis-specific region of difference 1 (RD1), such aspe35,cfp10, andesat6. In this study,pe35,cfp10, andesat6genes were cloned into shuttle plasmid pDE22 to generate the recombinant plasmids PDE22-PE35, PDE22-CFP10, and PDE22-ESAT6, which were electroporated into BCG to generate recombinant BCGs (rBCGs). The cellular immune responses (antigen-induced proliferation and secretion of selected T helper 1 [Th1], Th2, and anti-inflammatory cytokines, i.e., gamma interferon [IFN-γ], interleukin 5 [IL-5], and IL-10, respectively) that are specific to the proteins of cloned genes were studied by using spleen cells from mice immunized with native BCGs and rBCGs and synthetic peptides covering the protein sequence of the cloned genes. The results showed that the spleen cells did not secrete IL-5, whereas IL-10 was secreted in response to peptides of all three proteins from mice immunized with rBCGs only, suggesting expression of the cloned genes andin vivopriming of spleen cells to the expressed proteins. However, in Th1 cell assays that correlate with protective cellular immune responses, i.e., antigen-induced proliferation and IFN-γ secretion, only mice immunized with rBCG-pDE22-PE35 yielded positive responses to the peptides of PE35. These results suggest that rBCG-PDE22-PE35 is the only one of the three vaccines used in this work that is worthy of consideration as a new vaccine candidate against TB.

scholarly journals Enhanced Effect of DNA Immunization plusIn VivoElectroporation with a Combination of Hepatitis B Virus Core-PreS1 and S-PreS1 Plasmids

2011 ◽  
Vol 18 (11) ◽  
pp. 1789-1795 ◽  
Author(s):  
Hong Chen ◽  
Bo Wen ◽  
Yao Deng ◽  
Wen Wang ◽  
Xiao Yin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Therapeutic Vaccine ◽  
Intradermal Injection ◽  
Hbv Dna ◽  
Dna Immunization ◽  
Virus Core ◽  
Specific Cellular Immune Response ◽  
T Cell Immune Responses ◽  
Cellular Immune ◽  
Antibody Levels

ABSTRACTTo develop a novel, effective HBV therapeutic vaccine, we constructed two HBV DNA immunogens that contained PreS1, HBSS1, and HBCS1. Several delivery methods, such as intramuscular (i.m.) injection, intramuscular injection plus electroporation (i.m.-EP), and intradermal injection plus electroporation (i.d.-EP) were used in a murine model to analyze and compare the immune responses that were induced by the DNA immunogens. We found that i.d.-EP accelerated specific antibody seroconversion and produced high antibody (anti-PreS1, anti-S, and anti-C antibody) titers after HBSS1 and HBCS1 immunization. Combining the HBSS1 and HBCS1 DNA immunogens with i.d.-EP produced the strongest multiantigen (PreS1, S, and C)-specific cellular immune response and the highest specific PreS1 antibody levels. The results indicated that DNA immunization using HBSS1 and HBCS1 might be an ideal candidate, with its ability to elicit robust B and T cell immune responses against multiantigen when combined with optimized delivery technology. The present study provides a basis for the design and rational application of a novel HBV DNA vaccine.

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