Early Pulmonary Cytokine and Chemokine Responses in Mice Immunized with Three Different Vaccines against Mycobacterium tuberculosis Determined by PCR Array

ABSTRACT In this study, the early pulmonary cytokine and chemokine responses in mice immunized with either BCG vaccine, a ΔsecA2 mutant of Mycobacterium tuberculosis, or a DNA vaccine expressing an ESAT6-antigen 85B fusion protein and then aerogenically challenged with a low dose of M. tuberculosis were evaluated by PCR array. The cellular immune responses at day 10 postchallenge were essentially equivalent in the lungs of mice immunized with either the highly immunogenic BCG vaccine or the ΔsecA2 M. tuberculosis mutant strain. Specifically, 12 immune biomolecules (including gamma interferon [IFN-γ], interleukin-21 [IL-21], IL-27, IL-17f, CXCL9, CXCL10, and CXCL11) were differentially regulated, relative to the levels for naïve controls, in the lungs of vaccinated mice at this time point. Although the vaccine-related immune responses evoked in mice immunized with the DNA vaccine were relatively limited at 10 days postinfection, upregulation of IFN-γ RNA synthesis as well as increased expression levels of CXCL9, CXCL10, and CXCL11 chemokines were detected.

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A DNA Vaccine-Encoded Nucleoprotein of Influenza Virus Fails To Induce Cellular Immune Responses in a Diabetic Mouse Model

Clinical and Vaccine Immunology ◽

10.1128/cvi.00445-09 ◽

2010 ◽

Vol 17 (4) ◽

pp. 683-687 ◽

Cited By ~ 5

Author(s):

Abbas Jamali ◽

Farzaneh Sabahi ◽

Taravat Bamdad ◽

Hamidreza Hashemi ◽

Fereidoun Mahboudi ◽

...

Keyword(s):

Influenza Virus ◽

Virus Infection ◽

Immune Responses ◽

Dna Vaccine ◽

Lymphocyte Proliferation ◽

Influenza Virus Infection ◽

Diabetic Mice ◽

Cellular Immune Responses ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Influenza virus infections cause yearly epidemics and are a major cause of lower respiratory tract illnesses in humans worldwide. Influenza virus has long been recognized to be associated with higher morbidity and mortality in diabetic patients. Vaccination is an effective tool to prevent influenza virus infection in this group of patients. Vaccines employing recombinant-DNA technologies are an alternative to inactivated virus and live attenuated virus vaccines. Internal highly conserved viral nucleoprotein (NP) can be delivered as a DNA vaccine to provide heterosubtypic immunity, offering resistance against various influenza virus strains. In this study, we investigated the efficacy of an NP DNA vaccine for induction of cell-mediated immune responses and protection against influenza virus infection in a mouse model of diabetes. Healthy and diabetic BALB/c mice were immunized on days 0, 14, and 28 by injection of NP DNA vaccine. Two weeks after the last immunization, the cellular immune response was evaluated by gamma interferon (IFN-γ), lymphocyte proliferation, and cytotoxicity assays. The mice were challenged with influenza virus, and the viral titers in the lungs were measured on day 4. Diabetic mice showed significantly smaller amounts of IFN-γ production, lymphocyte proliferation, and cytotoxicity responses than nondiabetic mice. Furthermore, higher titers of the influenza virus were detected after challenge in the lungs of the diabetic mice. The present data suggest that the NP DNA vaccine with the protocol of immunization described here is not able to induce efficient cellular immune responses against influenza virus infection in diabetic mice.

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Characterization of Human Cellular Immune Responses to Novel Mycobacterium tuberculosis Antigens Encoded by Genomic Regions Absent in Mycobacterium bovis BCG

Infection and Immunity ◽

10.1128/iai.00199-08 ◽

2008 ◽

Vol 76 (9) ◽

pp. 4190-4198 ◽

Cited By ~ 32

Author(s):

R. Al-Attiyah ◽

A. S. Mustafa

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Mycobacterium Bovis ◽

Healthy Subjects ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Necrosis Factor Alpha ◽

Cellular Immune Responses ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Comparative genomics has identified several regions of differences (RDs) between the infectious Mycobacterium tuberculosis and the vaccine strains of Mycobacterium bovis BCG. We aimed to evaluate the cellular immune responses induced by antigens encoded by genes predicted in 11 RDs. Synthetic peptides covering the sequences of RD1, RD4 to RD7, RD9 to RD13, and RD15 were tested for antigen-induced proliferation and secretion of Th1 cytokine, gamma interferon (IFN-γ), by peripheral blood mononuclear cells (PBMC) obtained from culture-proven pulmonary tuberculosis (TB) patients and M. bovis BCG-vaccinated healthy subjects. Among the peptide pools, RD1 induced the best responses in both donor groups and in both assays. In addition, testing of TB patients' PBMC for secretion of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin 6 [IL-6], IL-8, and IL-1β), Th1 cytokines (IFN-γ, IL-2, and TNF-β), and Th2 cytokines (IL-4, IL-5, and IL-10) showed differential effects of RD peptides in the secretion of IFN-γ and IL-10, with high IFN-γ/IL-10 ratios (32 to 5.0) in response to RD1, RD5, RD7, RD9, and RD10 and low IFN-γ/IL-10 ratios (<1.0) in response to RD12, RD13, and RD15. Peptide-mixing experiments with PBMC from healthy subjects showed that secretion of large quantities of IL-10 in response to RD12 and RD13 correlated with inhibition of Th1 responses induced by RD1 peptides. In conclusion, our results suggest that M. tuberculosis RDs can be divided into two major groups—one group that activates PBMC to preferentially secrete IFN-γ and another group that activates preferential secretion of IL-10—and that these two groups of RDs may have roles in protection against and pathogenesis of TB, respectively.

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A polyvalent influenza DNA vaccine applied by needle-free intradermal delivery induces cross-reactive humoral and cellular immune responses in pigs

Vaccine ◽

10.1016/j.vaccine.2016.05.030 ◽

2016 ◽

Vol 34 (32) ◽

pp. 3634-3640 ◽

Cited By ~ 8

Author(s):

Marie Borggren ◽

Jens Nielsen ◽

Ingrid Karlsson ◽

Tina S. Dalgaard ◽

Ramona Trebbien ◽

...

Keyword(s):

Immune Responses ◽

Dna Vaccine ◽

Cellular Immune Responses ◽

Intradermal Delivery ◽

Cellular Immune

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Cellular Immune Responses to Nine Mycobacterium tuberculosis Vaccine Candidates following Intranasal Vaccination

PLoS ONE ◽

10.1371/journal.pone.0022718 ◽

2011 ◽

Vol 6 (7) ◽

pp. e22718 ◽

Cited By ~ 22

Author(s):

Suraj B. Sable ◽

Mani Cheruvu ◽

Subhadra Nandakumar ◽

Sunita Sharma ◽

Kakali Bandyopadhyay ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Vaccine Candidates ◽

Cellular Immune Responses ◽

Cellular Immune

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Perinatal oral exposure to low doses of bisphenol A, S or F impairs gut barrier and immune functions in female offspring mice

10.21203/rs.2.17347/v1 ◽

2019 ◽

Author(s):

Yann Malaisé ◽

Corinne Lencina ◽

Christel Cartier ◽

Maïwenn Olier ◽

Sandrine Ménard ◽

...

Keyword(s):

Adverse Effects ◽

Immune Responses ◽

Bisphenol A ◽

Low Dose ◽

Intestinal Barrier ◽

Female Offspring ◽

Oral Exposure ◽

Gut Barrier ◽

Cellular Immune Responses ◽

Cellular Immune

Abstract Background Bisphenol A (BPA), one of the highest-volume chemicals produced worldwide, has been identified as an endocrine disruptor. Many peer-reviewing studies have reported adverse effects of low dose BPA exposure, particularly during perinatal period (gestation and/or lactation). We previously demonstrated that perinatal oral exposure to BPA (via gavage of mothers during gestation and lactation) has long-term consequences on immune response and intestinal barrier functions. Due to its adverse effects on several developmental and physiological processes, BPA was removed from consumer products and replaced by chemical substitutes such as BPS or BPF, that are structurally similar and not well studied compare to BPA. Here, we aimed to compare perinatal oral exposure to these bisphenols (BPs) at two doses (5 and 50 mg/kg body weight (BW)/day (d)) on gut barrier and immune system in female offspring mice at adulthood (Post Natal Day PND70). Methods Pregnant female mice were orally exposed to BPA, BPS or BPF at 5 or 50 μg/kg BW/d from 15th day of gravidity to weaning of pups at PostNatal Day (PND) 21. Gut barrier function and the humoral and cellular immune responses of adult offspring (PND70) were analysed at intestinal and systemic levels. Results In female offspring, perinatal oral BP exposure led to adverse effects on intestinal barrier and immune response that were dependant of the BP nature (A, S or F) and dose of exposure. Stronger impacts were observed with BPS at the dose of 5µg/kg BW/d on inflammatory markers in feces associated with an increase of anti-E. coli IgG, revealing a defect of gut barrier. BPA and BPF exposure induced prominent changes at low dose in offspring mice, in term of gut barrier functions and cellular immune responses, provoking an intestinal and systemic Th1/Th17 inflammation. Conclusion These findings provide, for the first time, a comparative study of long-time consequences of BPA, S and F perinatal exposure by oral route in offspring mice. This work warms that it is mandatory to consider immune markers and dose in risk assessment associated to new BPA’s alternatives. Keywords: Bisphenol A, Bisphenol S, Bisphenol F, Immune responses, Perinatal exposure, Intestine, Th1/Th17, immunoglobulin, cytokines

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The Mycobacterium tuberculosis Recombinant 27-Kilodalton Lipoprotein Induces a Strong Th1-Type Immune Response Deleterious to Protection

Infection and Immunity ◽

10.1128/iai.71.6.3146-3154.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3146-3154 ◽

Cited By ~ 55

Author(s):

Avi-Hai Hovav ◽

Jacob Mullerad ◽

Liuba Davidovitch ◽

Yolanta Fishman ◽

Fabiana Bigi ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Immune Responses ◽

Interleukin 10 ◽

Control Groups ◽

Cellular Immune Responses ◽

Protective Antigens ◽

Proliferation Response ◽

Cellular Immune ◽

Mycobacterial Antigens

ABSTRACT Th1 immune response is essential in the protection against mycobacterial intracellular pathogens. Lipoproteins trigger both humoral and cellular immune responses and may be candidate protective antigens. We studied in BALB/c mice the immunogenicity and the protection offered by the recombinant 27-kDa Mycobacterium tuberculosis lipoprotein and the corresponding DNA vaccine. Immunization with the 27-kDa antigen resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a with a typical Th1 profile and a strong delayed hypersensitivity response. A strong proliferation response was observed in splenocytes, and significant nitric oxide production and gamma interferon secretion but not interleukin 10 secretion were measured. Based on these criteria, the 27-kDa antigen induced a typical Th1-type immune response thought to be necessary for protection. Surprisingly, in 27-kDa-vaccinated mice (protein or DNA vaccines) challenged by M. tuberculosis H37Rv or BCG strains, there was a significant increase in the numbers of CFU in the spleen compared to that for control groups. Furthermore, the protection provided by BCG or other mycobacterial antigens was completely abolished once the 27-kDa antigen was added to the vaccine preparations. This study indicates that the 27-kDa antigen has an adverse effect on the protection afforded by recognized vaccines. We are currently studying how the 27-kDa antigen modulates the mouse immune response.

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Simultaneous Administration of Recombinant Measles Viruses Expressing Respiratory Syncytial Virus Fusion (F) and Nucleo (N) Proteins Induced Humoral and Cellular Immune Responses in Cotton Rats

Vaccines ◽

10.3390/vaccines7010027 ◽

2019 ◽

Vol 7 (1) ◽

pp. 27 ◽

Cited By ~ 2

Author(s):

Yoshiaki Yamaji ◽

Akihito Sawada ◽

Yosuke Yasui ◽

Takashi Ito ◽

Tetsuo Nakayama

Keyword(s):

Respiratory Syncytial Virus ◽

Immune Responses ◽

Neutralizing Antibodies ◽

Simultaneous Administration ◽

Cellular Immune Responses ◽

Immunization Group ◽

Cotton Rats ◽

Ifn Γ ◽

Syncytial Virus ◽

Cellular Immune

We previously reported that recombinant measles virus expressing the respiratory syncytial virus (RSV) fusion protein (F), MVAIK/RSV/F, induced neutralizing antibodies against RSV, and those expressing RSV-NP (MVAIK/RSV/NP) and M2-1 (MVAIK/RSV/M2-1) induced RSV-specific CD8+/IFN-γ+ cells, but not neutralizing antibodies. In the present study, MVAIK/RSV/F and MVAIK/RSV/NP were simultaneously administered to cotton rats and immune responses and protective effects were compared with MVAIK/RSV/F alone. Sufficient neutralizing antibodies against RSV and RSV-specific CD8+/IFN-γ+ cells were observed after re-immunization with simultaneous administration. After the RSV challenge, CD8+/IFN-γ+ increased in spleen cells obtained from the simultaneous immunization group in response to F and NP peptides. Higher numbers of CD8+/IFN-γ+ and CD4+/IFN-γ+ cells were detected in lung tissues from the simultaneous immunization group after the RSV challenge. No detectable RSV was recovered from lung homogenates in the immunized groups. Mild inflammatory reactions with the thickening of broncho-epithelial cells and the infiltration of inflammatory cells were observed in lung tissues obtained from cotton rats immunized with MVAIK/RSV/F alone after the RSV challenge. No inflammatory responses were observed after the RSV challenge in the simultaneous immunization groups. The present results indicate that combined administration with MVAIK/RSV/F and MVAIK/RSV/NP induces humoral and cellular immune responses and shows effective protection against RSV, suggesting the importance of cellular immunity.

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Strong HCV NS3- and NS4A-specific cellular immune responses induced in mice and Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine

Vaccine ◽

10.1016/j.vaccine.2008.07.052 ◽

2008 ◽

Vol 26 (49) ◽

pp. 6225-6231 ◽

Cited By ~ 28

Author(s):

Krystle A. Lang ◽

Jian Yan ◽

Ruxandra Draghia-Akli ◽

Amir Khan ◽

David B. Weiner

Keyword(s):

Immune Responses ◽

Dna Vaccine ◽

Rhesus Macaques ◽

Hcv Genotype ◽

Cellular Immune Responses ◽

Genotype 1A ◽

Cellular Immune

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Augmented humoral and cellular immune responses of a hepatitis B DNA vaccine encoding HBsAg by protein boosting

Vaccine ◽

10.1016/j.vaccine.2004.10.013 ◽

2005 ◽

Vol 23 (14) ◽

pp. 1649-1656 ◽

Cited By ~ 19

Author(s):

He Xiao-wen ◽

Sun Shu-han ◽

Hu Zhen-lin ◽

Li Jun ◽

Jiang Lei ◽

...

Keyword(s):

Hepatitis B ◽

Immune Responses ◽

Dna Vaccine ◽

Cellular Immune Responses ◽

Cellular Immune

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Humoral and Cellular Immune Responses to Trypanosoma cruzi-Derived Paraflagellar Rod Proteins in Patients with Chagas' Disease

Infection and Immunity ◽

10.1128/iai.71.6.3165-3171.2003 ◽

2003 ◽

Vol 71 (6) ◽

pp. 3165-3171 ◽

Cited By ~ 34

Author(s):

Vladimir Michailowsky ◽

Keith Luhrs ◽

Manoel Otávio C. Rocha ◽

David Fouts ◽

Ricardo T. Gazzinelli ◽

...

Keyword(s):

Trypanosoma Cruzi ◽

Immune Responses ◽

Chagas Disease ◽

Mononuclear Cells ◽

Clinical Symptoms ◽

Cellular Responses ◽

Peripheral Blood Mononuclear ◽

Cellular Immune Responses ◽

Ifn Γ ◽

Cellular Immune

ABSTRACT Sera and peripheral blood mononuclear cells (PBMC) from patients displaying different clinical symptoms as well as from normal uninfected individuals (NI) were used to evaluate the humoral and cellular responses of Chagas' disease patients to Trypanosoma cruzi-derived paraflagellar rod proteins (PFR). Our results show that sera from both asymptomatic Chagas' disease patients (ACP) and cardiac Chagas' disease patients (CCP) have higher levels of antibodies to PFR than sera from NI. Immunoglobulin G1 (IgG1) and IgG3 were the main Ig isotypes that recognized PFR. We also tested three recombinant forms of PFR, named rPAR-1, rPAR-2, and rPAR-3, by Western blot analysis. Sera from seven out of eight patients with Chagas' disease recognized one of the three rPAR forms. Sera from 75, 50, and 37.5% of Chagas' disease patients tested recognized rPAR-3, rPAR-2, and rPAR-1, respectively. PFR induced proliferation of 100 and 70% of PBMC from ACP and CCP, respectively. Further, stimulation of cells from Chagas' disease patients with PFR enhanced the frequencies of both small and large CD4+ CD25+ and CD4+ CD69+ lymphocytes, as well as that of small CD8+ CD25+ lymphocytes. Finally, we evaluated the ability of PFR to elicit the production of gamma interferon (IFN-γ) by PBMC from patients with Chagas' disease. Fifty percent of the PBMC from ACP as well as CCP produced IFN-γ upon stimulation with PFR. PFR enhanced the percentages of IFN-γ-producing cells in both CD3+ and CD3− populations. Within the T-cell population, large CD4+ T lymphocytes were the main source of IFN-γ.

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