scholarly journals Peptides-Based Vaccine MP3RT Induced Protective Immunity Against Mycobacterium Tuberculosis Infection in a Humanized Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Wenping Gong ◽  
Yan Liang ◽  
Jie Mi ◽  
Zaixing Jia ◽  
Yong Xue ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Lymphocytes ◽  
Binding Capacity ◽  
Protective Efficacy ◽  
Humanized Mice ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Beings ◽  
Wild Type ◽  
New Findings ◽  
Ifn Γ

BackgroundTuberculosis (TB) is still a global infectious disease that seriously threatens human beings. The only licensed TB vaccine Bacille Calmette-Guérin (BCG)’s protective efficacy varies significantly among populations and regions. It is very urgent to develop more effective vaccines.MethodsIn this study, eleven candidate proteins of Mycobacterium tuberculosis were selected to predict peptides with high-affinity binding capacity for the HLA-DRB1*01:01 molecule. The immunodominant peptides were identified with the enzyme-linked immunospot assay (ELISPOT) and linked in silico to result in a novel polypeptide vaccine in Escherichia coli cells. The vaccine’s protective efficacy was evaluated in humanized and wild-type C57BL/6 mice. The potential immune protective mechanisms were explored with Enzyme-linked Immunosorbent Assay (ELISA), flow cytometry, and ELISPOT.ResultsSix immunodominant peptides screened from 50 predicted peptides were used to construct a new polypeptide vaccine named MP3RT. After challenge with M. tuberculosis, the colony-forming units (CFUs), lung lesion area, and the number of inflammatory cells in humanized mice rather than wild-type mice vaccinated with MP3RT were significantly lower than these in mice immunized with PBS. The humanized mice vaccinated with MP3RT revealed significant increases in IFN-γ cytokine production, IFN-γ+ T lymphocytes, CD3+IFN-γ+ T lymphocytes, and the MP3RT-specific IgG antibody.ConclusionsTaken together, MP3RT is a promising peptides-based TB vaccine characterized by inducing high levels of IFN-γ and CD3+IFN-γ+ T lymphocytes in humanized mice. These new findings will lay a foundation for the development of peptides-based vaccines against TB.

scholarly journals Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from Mycobacterium tuberculosis Beijing/K Strain in Mice

2017 ◽  
Vol 24 (11) ◽  
Author(s):  
Ahreum Kim ◽  
Yun-Gyoung Hur ◽  
Sunwha Gu ◽  
Sang-Nae Cho
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
T Cell Epitopes ◽  
Content Type ◽  
Complete Form ◽  
Ifn Γ

ABSTRACT The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tuberculosis-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (P < 0.05) and recalled gamma interferon (IFN-γ), interleukin-2 (IL-2), IL-6, and IL-17 responses (P < 0.05 or P < 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log10 reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4+ T cells producing protective cytokines, such as IFN-γ and IL-17, in lungs and spleens (P < 0.01) and CD4+ multifunctional T cells producing IFN-γ, tumor necrosis factor alpha (TNF-α), and/or IL-17 (P < 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN-γ production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses in vivo, may be informative for vaccine development, particularly in regions where the M. tuberculosis Beijing/K-strain is frequently isolated from TB patients.

scholarly journals PERCENTAGE OF CD3+ T LYMPHOCYTES EXPRESSING IFN-γ AFTER CFP-10 STIMULATION (Persentase Limfosit T-CD3+ yang Mengekspresikan Interferon Gamma Setelah Stimulasi Antigen CFP-10)

2018 ◽  
Vol 23 (1) ◽  
pp. 31
Author(s):  
Yulia Nadar Indrasari ◽  
Betty Agustina Tambunan ◽  
Jusak Nugraha ◽  
Fransiska Sri Oetami
Keyword(s):  
Flow Cytometry ◽  
Mycobacterium Tuberculosis ◽  
T Lymphocytes ◽  
Interferon Gamma ◽  
Tuberculosis Antigen ◽  
Mycobacterium Tuberculosis Antigen ◽  
Ifn Γ

Tuberkulosis (TB) merupakan penyakit infeksi menular, disebabkan oleh Mycobacterium tuberculosis. Respons imun adaptif yangdiperantarai oleh limfosit T berperan sangat penting dalam menyingkirkan bakteri intraseluler. Hasilan sitokin IFN-γ merupakanmekanisme efektor utama dari limfosit T. Pengembangan vaksin yang efektif dalam melawan infeksi TB mempertimbangkan faktor yangmengatur hasilan IFN-γ. CFP-10 merupakan antigen yang disekresikan oleh Mycobacterium tuberculosis. Antigen ini dikenal sebagaikomponen vaksin potensial untuk TB. Tujuan penelitian ini adalah membandingkan respons imun seluler yaitu persentase limfosit T-CD3+yang mengekspresikan IFN-γ setelah dirangsang antigen CFP-10 di pasien TB paru kasus baru, TB laten dan orang sehat. Penelitianini menggunakan desain eksperimen murni di laboratorium secara in vitro pada kultur PBMC pasien TB paru kasus baru, TB latendan orang sehat. Subjek penelitian adalah 8 pasien TB paru kasus baru, 7 TB laten dan 7 orang sehat di RS Khusus Paru Surabaya.Pemeriksaan persentase limfosit T-CD3+ yang mengekspresikan IFN-γ dengan metode Flow cytometry (BD FACSCalibur). Hasil dianalisisdengan Kruskal-Wallis atau ANOVA satu arah. Rerata persentase limfosit T-CD3+ yang mengekspresikan IFN-γ di TB paru kasus barusetelah stimulasi antigen CFP-10 (4,36%) lebih tinggi daripada sebelum stimulasi (3,50%) (nilai P=0,015). Rerata persentase limfositT-CD3+ yang mengekspresikan IFN-γ di TB laten setelah stimulasi antigen CFP-10 (3,96%) lebih tinggi dibandingkan sebelum stimulasi(2,50%) tetapi tidak bermakna (nilai P=0,367). Rerata persentase limfosit T- CD3+ yang mengekspresikan IFN-γ di orang sehat setelahstimulasi (1,66%) lebih rendah daripada sebelum stimulasi (2,89%) tetapi tidak bermakna (nilai P=0,199). Perubahan persentaselimfosit T-CD3+ yang mengekspresikan IFN-γ setelah stimulasi antigen CFP-10 antarkelompok tidak berbeda bermakna (nilai P=0,143).Berdasarkan hasil telitian ini dapat disimpulkan bahwa terdapat peningkatan persentase limfosit T-CD3+ yang mengekspresikan IFN-γdi TB paru kasus baru setelah stimulasi antigen CFP-10. Hal ini menunjukkan limfosit T-CD3+ yang mengekspresikan IFN-γ berperandalam perlindungan terhadap infeksi TB paru.

scholarly journals Evaluation of a lateral flow assay for rapid and simple detection of IFN-γ for the diagnosis of Mycobacterium tuberculosis infection

2020 ◽  
Author(s):  
Jeong-Ran Kim ◽  
Hae Yeong Kang ◽  
Su-Bin Seong ◽  
Nari Kim ◽  
Tae Sun Shim ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lateral Flow ◽  
Lateral Flow Assay ◽  
Tuberculosis Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mycobacterium Tuberculosis Infection ◽  
Blood Samples ◽  
Simple Detection ◽  
Laboratory Workers ◽  
Ifn Γ

Abstract Background: Interferon-gamma (IFN-γ) release assays (IGRAs) are useful for the diagnosis of Mycobacterium tuberculosis infection. Current IGRAs use either enzyme-linked immunosorbent assay (ELISA) or enzyme-linked immunospot assay, which require complex procedures and techniques to determine IFN-γ secretion. We aimed to compare the usefulness of the easy-to-use lateral flow assay (LFA) with that of the QuantiFERON-TB Gold In-Tube (QFT-GIT) or QuantiFERON-TB Gold Plus (QFT-plus) ELISAs for detecting IFN-γ, produced by the blood T cells stimulated by tuberculosis (TB) antigen. Methods: Following informed consent, 176 participants, including health care workers such as TB laboratory workers and radiologists, were enrolled for the study from June 2017 to June 2018. Blood samples were collected and tested using QFT-GIT and QFT-plus. The secreted IFN-γ was quantified by LFA, which took approximately 15 min, and ELISA, which took approximately 3 h. Results: A total of 176 blood samples were screened. The positive rates of QFT-GIT and QFT-plus were 34.1% and 37.5%, respectively. Overall agreement between QFT-GIT and QFT-plus was 93.1% ( κ = 0.86). The positive rates of LFA with QFT-GIT tube and QFT-plus tube were 25.6% and 31.3%, respectively, overall agreement of LFA being 90.3% ( κ = 0.78) and 89.2% ( κ = 0.77), respectively, compared to the QFT-GIT and QFT-plus ELISA. Conclusion: The ability of LFA to measure IFN-γ was similar to that of ELISA. The current findings suggested that the new LFA could be more conveniently utilized for diagnosing TB infection.

scholarly journals Fusion Cytokines IL-7-Linker-IL-15 Promote Mycobacterium Tuberculosis Subunit Vaccine to Induce Central Memory like T Cell-Mediated Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 715
Author(s):  
Chunxiang Bai ◽  
Lijun Zhou ◽  
Junxia Tang ◽  
Juanjuan He ◽  
Jiangyuan Han ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Central Memory ◽  
Control Group ◽  
Cell Mediated Immunity ◽  
Protein Subunit ◽  
Subunit Vaccines ◽  
Ifn Γ

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is among the most serious infectious diseases worldwide. Adjuvanted protein subunit vaccines have been demonstrated as a kind of promising novel vaccine. This study proposed to investigate whether cytokines interliukine-7 (IL-7) and interliukine-15 (IL-15) help TB subunit vaccines induce long-term cell-mediated immune responses, which are required for vaccination against TB. In this study, mice were immunized with the M. tuberculosis protein subunit vaccines combined with adnovirus-mediated cytokines IL-7, IL-15, IL-7-IL-15, and IL-7-Linker-IL-15 at 0, 2, and 4 weeks, respectively. Twenty weeks after the last immunization, the long-term immune responses, especially the central memory-like T cells (TCM like cell)-mediated immune responses, were determined with the methods of cultured IFN-γ-ELISPOT, expanded secondary immune responses, cell proliferation, and protective efficacy against Mycobacterium bovis Bacilli Calmette-Guerin (BCG) challenge, etc. The results showed that the group of vaccine + rAd-IL-7-Linker-IL-15 induced a stronger long-term antigen-specific TCM like cells-mediated immune responses and had higher protective efficacy against BCG challenge than the vaccine + rAd-vector control group, the vaccine + rAd-IL-7 and the vaccine + rAd-IL-15 groups. This study indicated that rAd-IL-7-Linker-IL-15 improved the TB subunit vaccine’s efficacy by augmenting TCM like cells and provided long-term protective efficacy against Mycobacteria.

scholarly journals Role of Interferon-Gamma (Ifn-γ) in Immune Response Regulation in Hiv-1 and Hiv-1 + Mycobacterium Tuberculosis (Tb) Infected Patients / Interferona-gamma (Ifn-γ) Loma Imūnās Atbildes Regulēšanā Pacientiem Ar HIV-1 un HIV-1 + mycobacterium Tuberculosis

2016 ◽  
Vol 70 (4) ◽  
pp. 211-214
Author(s):  
Inga Januškevica ◽  
Baiba Rozentāle ◽  
Elvīra Hagina ◽  
Jeīena Eglīte ◽  
Tatjana Kolupajeva ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Viral Load ◽  
University Hospital ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Ifn Γ ◽  
Cd4 Cell ◽  
Hiv 1

Abstract The aim of this research was to investigate the role of IFN-γ in interaction between IL-10, IL-18, IL-1b, CD4 cell counts and HIV-1 RNA viral load in the development of HIV-1 in patients co-infected with Mycobacterium tuberculosis (TB). The study was conducted by Rīga East Clinical University Hospital with data from the HIV-1 register, in collaboration with the RSU Joint Laboratory of Clinical Immunology and Immunogenetics. 200 HIV-1 infected patients and 184 HIV-1 with TB co-infection patients divided in four groups were included in the study. IFN-γ, IL-10, IL-18, IL-1b levels were measured in serum with commercially enzyme-linked immunosorbent assay (ELISA Vector-Best Corporation, Novosibirsk, Russia). CD4 cell counts were measured by flow Partec IVD cytometry (USA). HIV-1 RNA quantification was performed using the COBAS AmpliPrep/COBAS Taqman HIV-1 Test (Germany). All groups were compared with each another. IFN-γ production was significantly lower, and IL-10 and CD4 cell counts were significantly higher, in HIV-1 patients without TB compared with the other groups. The group with HIV-1 and TB had significantly elevated IL-18 production. HIV patients with primary TB had significantly elevated IFN-γ production and HIV-1 RNA viral load and significantly lower IL-10 production.

Tryptophan Metabolites Analogue, N-(3,4-dimethoxycinnamonyl) Anthranilic Acid, Ameliorates Acute Graft-Versus-Host Disease Through Inhibiting Th1 Responses

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5421-5421
Author(s):  
Jinhuan Xu ◽  
Yicheng Zhang
Keyword(s):  
T Lymphocytes ◽  
Graft Versus Host Disease ◽  
Anthranilic Acid ◽  
Allogeneic Bone Marrow Transplantation ◽  
Enzyme Linked Immunosorbent Assay ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Ifn Γ ◽  
Acute Graft

Abstract Local catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is considered an important mechanism of regulating T cell immunity. N-(3,4-dimethoxycinnamonyl) anthranilic acid (3,4-DAA) is an active synthetic anthranilic acid derivative which was proved to be effective to treat type±helper T lymphocytes (Th1) mediated autoimmune diseases such as multiple sclerosis. In this report, we investigated the effects of 3,4-DAA on the acute graft versus host disease (aGVHD) following allogeneic bone marrow transplantation (allo-BMT) and its potential mechanism of action. we established a murine aGVHD model, 3,4-DAA was injected intraperitoneally at 200 mg/kg/day per mouse immediately after allo-BMT or at the onset of aGVHD for 14 consecutive days; the signs of aGVHD and the survival were recorded periodically; the histological changes of target organs were evaluated with hematoxylin-eosin staining; the IDO activity and cytokine levels in plasma were measured by reverse-phase high-performance liquid chromatography (HPLC) and enzyme linked immunosorbent assay (ELISA), respectively. We revealed that administration of 3,4-DAA after allo-BMT significantly reduced the severity and the histological score of aGVHD; The survival for mice receiving 3,4-DAA prophylaxis and treatment were prolonged in comparison to the vehicle control mice. The plasma levels of IFN-γ, TNF-α, IL-12 and IL-2 in 3,4-DAA treatment group were found to be decreased, while the IDO activity, the IL-10, IL-5 and IL-4 levels elevated in these mice. In consistent with the in vivo results, 3,4-DAA also inhibited IFN-γ and IL-2 production of spleen T lymphocytes in vitro. Our findings suggest that 3,4-DAA can diminish the murine experimental aGVHD through inhibition of Th1 response; this property makes it a potential alternative agent for prevention and treatment of GVHD in the clinic. Disclosures: No relevant conflicts of interest to declare.

Aspirin Blocks Orthodontic Relapse via Inhibition of CD4+ T Lymphocytes

2017 ◽  
Vol 96 (5) ◽  
pp. 586-594 ◽  
Author(s):  
Y. Liu ◽  
T. Zhang ◽  
C. Zhang ◽  
S.S. Jin ◽  
R.L. Yang ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Relapse Rate ◽  
Immune Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Th1 Cells ◽  
Tnf Α ◽  
Inflammatory Drugs ◽  
Ifn Γ ◽  
Anti Inflammatory

Immunologic response plays an important role in orthodontic tooth movement (OTM) and relapse. Nonsteroidal anti-inflammatory drugs, such as aspirin, affect immune cells and clinical orthodontic treatment. However, the mechanisms by which nonsteroidal anti-inflammatory drugs regulate immune cells to affect orthodontic relapse are unclear. In this study, male Sprague-Dawley rats were grouped as relapse and relapse + aspirin for 10 d after 14 d of OTM. Silicone impressions of the rats’ maxillary dentitions were obtained to record the distance of OTM at the indicated time point. CD4+ T lymphocytes in spleen were examined by flow cytometry. Serum levels of type 1 T-helper (Th1) cell–associated cytokines tumor necrosis factor α (TNF-α), and interferon γ (IFN-γ) were determined through enzyme-linked immunosorbent assay. The effects of aspirin on CD4+ T and Th1 cells were also analyzed in vitro. Aspirin treatment significantly reduced the relapse rate. More interestingly, injection of CD25 neutralizing antibody basiliximab or TNF-α inhibitor etanercept can significantly reduce the relapse rate as well. Correspondingly, aspirin treatment significantly accelerated the decrease of orthodontic force–induced secretion of TNF-α and IFN-γ in serum and the expression of TNF-α and IFN-γ in periodontal ligament during relapse. Furthermore, aspirin treatment in vitro significantly repressed the differentiation of CD4+ T and Th1 cells. Overall, results indicated that aspirin treatment can block orthodontic relapse by regulating Th1 cells.

scholarly journals Respiratory Tract Infection with Mycoplasma pneumoniae in Interleukin-12 Knockout Mice Results in Improved Bacterial Clearance and Reduced Pulmonary Inflammation

2006 ◽  
Vol 75 (1) ◽  
pp. 236-242 ◽  
Author(s):  
C. M. Salvatore ◽  
M. Fonseca-Aten ◽  
K. Katz-Gaynor ◽  
A. M. Gomez ◽  
A. Mejias ◽  
...  
Keyword(s):  
Respiratory Disease ◽  
Mycoplasma Pneumoniae ◽  
Pulmonary Inflammation ◽  
Airway Hyperreactivity ◽  
Interleukin 12 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Ifn Γ

ABSTRACT Mycoplasma pneumoniae is a leading cause of pneumonia and is associated with asthma. Evidence links M. pneumoniae respiratory disease severity with interleukin-12 (IL-12) concentration in respiratory secretions. We evaluated the microbiologic, inflammatory, and pulmonary function indices of M. pneumoniae pneumonia in IL-12 (p35) knockout (KO) mice and wild-type (WT) mice to determine the role of IL-12 in M. pneumoniae respiratory disease. Eight-week-old wild-type BALB/c mice and 8-week-old IL-12 (p35) KO BALB/c mice were inoculated once intranasally with 107 CFU of M. pneumoniae. Mice were evaluated at days 2, 4, and 7 after inoculation. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic scores (HPS), BAL cytokine concentrations determined by enzyme-linked immunosorbent assay (tumor necrosis factor alpha [TNF-α], gamma interferon [IFN-γ], IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor) and plethysmography, before and after methacholine, to assess airway obstruction (AO) and airway hyperreactivity (AHR). IL-12 (p35) KO mice infected with M. pneumoniae were found to have significantly lower BAL M. pneumoniae concentrations compared with M. pneumoniae-infected WT mice. Lung HPS and the parenchymal pneumonia subscores (neutrophilic alveolar infiltrate), as well as AO, were significantly lower in infected KO mice. No difference was found for AHR. Infected KO mice had significantly lower BAL concentrations of IFN-γ than WT mice; a trend toward lower BAL concentrations was observed for IL-10 (P = 0.065) and TNF-α (P = 0.078). No differences were found for IL-1β, IL-2, IL-4, IL-5, or IL-6. The lack of IL-12 in experimental M. pneumoniae pneumonia was associated with less severe pulmonary disease and more rapid microbiologic and histologic resolution.

scholarly journals Response of human intestinal lamina propria T lymphocytes to interleukin 12: additive effects of interleukin 15 and 7

Gut ◽  
1998 ◽  
Vol 43 (5) ◽  
pp. 620-628 ◽  
Author(s):  
G Monteleone ◽  
T Parrello ◽  
F Luzza ◽  
F Pallone
Keyword(s):  
T Lymphocytes ◽  
Lamina Propria ◽  
Intestinal Inflammation ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Subunit Mrna ◽  
Mucosal Response ◽  
Interleukin 15 ◽  
Ifn Γ

Background/Aim—Interleukin (IL) 12 is involved in the mucosal response during intestinal inflammation but its role is not fully understood. The response of human lamina propria T lymphocytes (T-LPL) to IL-12 in terms of interferon γ (IFN-γ) release and proliferation was investigated, exploring whether IL-15 and IL-7 cooperate with IL-12. The role of accessory molecules (CD2 and CD28) was also investigated.Methods—Unstimulated and phytohaemagglutinin preactivated T-LPL cultures were incubated with or without the initial addition of cytokines, anti-CD2 or anti-CD28 antibodies. IFN-γ mRNA was detected by reverse transcriptase polymerase chain reaction, and protein secretion was measured by enzyme linked immunosorbent assay (ELISA).Results—IFN-γ mRNA was induced in T-LPLs by IL-12 and IL-15 but not IL-7, whereas IFN-γ was measured only in IL-12 stimulated T-LPL cultures. IL-12 induced IFN-γ release was not abrogated by neutralising anti-IL-2 antibody or by cyclosporin A. IL-12 synergised with either anti-CD2 or anti-CD28 antibodies in inducing IFN-γ synthesis. In preactivated T-LPLs, IL-7 enhanced IFN-γ release induced by both IL-12 and anti-CD2, whereas IL-15 potentiated only IL-12 induced IFN-γ synthesis. IL-12 did not induce proliferation of either unstimulated or preactivated T-LPLs and it did not enhance the CD2/CD28 stimulated T-LPL proliferative response. No transcript for IL-12 receptor β1 subunit was detected in freshly isolated and activated T-LPLs whereas the β2subunit mRNA was consistently found in T-LPL samples.Conclusions—IL-12 induces human T-LPLs to produce and release IFN-γ, and IL-15 and IL-7 cooperate with IL-12 in expanding the IFN-γ mucosal response.

scholarly journals Gamma Interferon and Monophosphoryl Lipid A-Trehalose Dicorynomycolate Are Efficient Adjuvants for Mycobacterium tuberculosis Multivalent Acellular Vaccine

2005 ◽  
Vol 73 (1) ◽  
pp. 250-257 ◽  
Author(s):  
Avi-Hai Hovav ◽  
Yolanta Fishman ◽  
Herve Bercovier
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Lipid A ◽  
Protective Efficacy ◽  
Gamma Interferon ◽  
No Production ◽  
Adjuvant Effect ◽  
Recombinant Antigens ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid ◽  
Ifn Γ

ABSTRACT In this study, we examined the immunogenicity and protective efficacy of six immunodominant Mycobacterium tuberculosis recombinant antigens (85B, 38kDa, ESAT-6, CFP21, Mtb8.4, and 16kDa) in a multivalent vaccine preparation (6Ag). Gamma interferon (IFN-γ) and monophosphoryl lipid A-trehalose dicorynomycolate (Ribi) adjuvant systems were used separately or in combination for immunization with the recombinant antigens. Our results demonstrate that immunization of mice with Ribi emulsified antigens in the presence of IFN-γ (Ribi+6Ag+IFN-γ) resulted after challenge with a virulent M. tuberculosis strain in a significant reduction in the CFU counts that was comparable to that achieved with the BCG vaccine (∼0.9-log protection). Antigen-specific immunoglobulin G (IgG) titers in the Ribi+6Ag+IFN-γ-immunized mice were lower than in mice immunized with Ribi+6Ag and were oriented toward a Th1-type response, as confirmed by elevated IgG2a levels. In addition, splenocyte proliferation, IFN-γ secretion, and NO production were significantly higher in splenocytes derived from Ribi+6Ag+IFN-γ-immunized mice, whereas IL-10 secretion was decreased. These findings confirm the induction of a strong cellular immunity in the vaccinated mice that correlates well with their enhanced resistance to M. tuberculosis. The adjuvant effect of IFN-γ was dose dependent. A dose of 5 μg of IFN-γ per mouse per immunization gave optimal protection, whereas lower or higher amounts (0.5 or 50 μg/ mouse) of IFN-γ failed to enhance protection.

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