scholarly journals Liposome-Mediated Delivery of MERS Antigen Induces Potent Humoral and Cell-Mediated Immune Response in Mice

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 403
Author(s):  
Masood Alam Khan ◽  
Ajamaluddin Malik ◽  
Mohammad A. Alzohairy ◽  
Abdulmohsen M. Alruwetei ◽  
Bader Y. Alhatlani ◽  
...  
Keyword(s):  
Immune Responses ◽  
Alanine Transaminase ◽  
Aspartate Transaminase ◽  
Carrier System ◽  
Cell Mediated Immune Response ◽  
Incomplete Freund’S Adjuvant ◽  
Ifn Γ ◽  
Specific Stimulation ◽  
Vaccine Carrier ◽  
Stimulation Of

The advancements in the field of nanotechnology have provided a great platform for the development of effective antiviral vaccines. Liposome-mediated delivery of antigens has been shown to induce the antigen-specific stimulation of the humoral and cell-mediated immune responses. Here, we prepared dried, reconstituted vesicles (DRVs) from DPPC liposomes and used them as the vaccine carrier system for the Middle East respiratory syndrome coronavirus papain-like protease (DRVs-MERS-CoV PLpro). MERS-CoV PLpro emulsified in the Incomplete Freund’s Adjuvant (IFA-MERS-CoV PLpro) was used as a control. Immunization of mice with DRVs-MERS-CoV PLpro did not induce any notable toxicity, as revealed by the levels of the serum alanine transaminase (ALT), aspartate transaminase (AST), blood urea nitrogen (BUN) and lactate dehydrogenase (LDH) in the blood of immunized mice. Immunization with DRVs-MERS-CoV PLpro induced greater antigen-specific antibody titer and switching of IgG1 isotyping to IgG2a as compared to immunization with IFA-MERS-CoV PLpro. Moreover, splenocytes from mice immunized with DRVs-MERS-CoV PLpro exhibited greater proliferation in response to antigen stimulation. Moreover, splenocytes from DRVs-MERS-CoV PLpro-immunized mice secreted significantly higher IFN-γ as compared to splenocytes from IFA-MERS-CoV PLpro mice. In summary, DRVs-MERS-CoV PLpro may prove to be an effective prophylactic formulation to prevent MERS-CoV infection.

scholarly journals Immune Responses Following BCG Immunization of Infants in Uganda and United Kingdom Are Similar for Purified Protein Derivative but Differ for Secretory Proteins of Mycobacterium tuberculosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrice A. Mawa ◽  
Mateusz Hasso-Agopsowicz ◽  
Lawrence Lubyayi ◽  
Grace Nabakooza ◽  
Marjorie Nakibuule ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
United Kingdom ◽  
Immune Responses ◽  
Secretory Proteins ◽  
Birth Cohorts ◽  
Bcg Vaccination ◽  
Ifn Γ ◽  
The Uk ◽  
Mycobacterial Antigens ◽  
Stimulation Of

Introduction: The immunogenicity of BCG vaccination in infants differs between populations. We hypothesized that prenatal exposure to mycobacterial antigens might explain the differences in immune responses to BCG seen in other studies of infants in Africa and the United Kingdom (UK) and we explored this in birth cohorts in Uganda and the UK.Materials and Methods: Blood samples were obtained from BCG-immunized infants of mothers with (n = 110) and without (n = 121) latent Mycobacterium tuberculosis infection (LTBI) in Uganda and BCG-immunized infants of mothers without LTBI (n = 25) in the UK at 10 and 52 weeks after birth. Cytokine and chemokine responses to PPD were measured to assess responses to BCG immunization, and to ESAT6/CFP10 to assess exposure to or infection with M. tuberculosis or non-tuberculous mycobacteria (NTM) in 6-day whole blood culture supernatants by a 17-plex Luminex assay. Median responses were compared between Ugandan infants (together, and separated by maternal LTBI status) and UK infants.Results: The IFN-γ response to BCG vaccination was similar between Ugandan and UK infants at 10 and 52 weeks. At week 52, TNF production was marginally higher in Ugandan infants, but after adjusting for multiple comparisons this difference was not significant. At weeks 10 and 52, stimulation of blood with ESAT6/CFP10 produced significantly higher IFN-γ, TNF, IL-12p40, IL-1α, IL-1β, IL-1Ra, IP-10, MIP-1α, MIP-1β, and GM-CSF in Ugandan compared to UK infants. Stimulation of blood with ESAT6/CFP10 produced significantly higher amounts of IL-8 (p = 0.0001), IL-10 (p = 0.0022), and IL-13 (p = 0.0020) in the UK than in Ugandan infants of mothers without LTBI at week 10, but not at week 52.Conclusions: Immune responses to mycobacterial antigens following BCG immunization are similar for PPD, but differ for ESAT6/CFP10, between infants in Uganda and the UK. Neither maternal LTBI nor infant exposure to or infection with mycobacteria impacts the response to BCG. The observed global differences in immune response to BCG immunization are likely to be due to other causes.

scholarly journals CpG Oligodeoxynucleotides Act as Adjuvants that Switch on T Helper 1 (Th1) Immunity

1997 ◽  
Vol 186 (10) ◽  
pp. 1623-1631 ◽  
Author(s):  
Rose S. Chu ◽  
Oleg S. Targoni ◽  
Arthur M. Krieg ◽  
Paul V. Lehmann ◽  
Clifford V. Harding
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cpg Odn ◽  
T Helper ◽  
T Helper 1 ◽  
Cpg Oligodeoxynucleotides ◽  
Cytokine Pattern ◽  
Incomplete Freund’S Adjuvant ◽  
Ifn Γ ◽  
Hen Egg

Synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG ODN) induce macrophages to secrete IL-12, which induces interferon (IFN)-γ secretion by natural killer (NK) cells. Since these cytokines can induce T helper 1 (Th1) differentiation, we examined the effects of coadministered CpG ODN on the differentiation of Th responses to hen egg lysozyme (HEL). In both BALB/c (Th2-biased) and B10.D2 (Th1-biased) mice, immunization with HEL in incomplete Freund's adjuvant (IFA) resulted in Th2-dominated immune responses characterized by HEL-specific secretion of IL-5 but not IFN-γ. In contrast, immunization with IFA-HEL plus CpG ODN switched the immune response to a Th1-dominated cytokine pattern, with high levels of HEL-specific IFN-γ secretion and decreased HEL-specific IL-5 production. IFA-HEL plus CpG ODN also induced anti-HEL IgG2a (a Th1-associated isotype), which was not induced by IFA-HEL alone. Control non–CpG ODN did not induce IFN-γ or IgG2a, excepting lesser increases in B10.D2 (Th1-biased) mice. Thus, CpG ODN provide a signal to switch on Th1-dominated responses to coadministered antigen and are potential adjuvants for human vaccines to elicit protective Th1 immunity.

VIP balances innate and adaptive immune responses induced by specific stimulation of TLR2 and TLR4

Peptides ◽  
2008 ◽  
Vol 29 (6) ◽  
pp. 948-956 ◽  
Author(s):  
Alicia Arranz ◽  
Yasmina Juarranz ◽  
Javier Leceta ◽  
Rosa P. Gomariz ◽  
Carmen Martínez
Keyword(s):  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Specific Stimulation ◽  
Stimulation Of

scholarly journals Cytokines in Mycoplasma hyorhinis-Induced Arthritis in Pigs Bred Selectively for High and Low Immune Responses

2000 ◽  
Vol 68 (3) ◽  
pp. 1150-1155 ◽  
Author(s):  
N. R. Jayagopala Reddy ◽  
Bruce N. Wilkie ◽  
Peter Borgs ◽  
Bonnie A. Mallard
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Cytokine Response ◽  
Mycoplasma Hyorhinis ◽  
Necrosis Factor Alpha ◽  
Susceptibility To Infection ◽  
Cell Mediated Immune Response ◽  
Tnf Α ◽  
Yorkshire Pigs ◽  
Ifn Γ

ABSTRACT Yorkshire pigs were bred selectively for high and low immune responses (H and L pigs, respectively) based on multiple antibody (Ab) and cell-mediated immune response traits. In a previous experiment, generation 4 (G4) pigs of each line were infected with Mycoplasma hyorhinis. High responders had a more rapid and higher Ab response and less polyserositis, but arthritis was more severe in H pigs than in L pigs. To test the hypothesis that line differences were attributable to differential expression of cytokines, M. hyorhinis infection was induced in pigs of G8. Arthritis was more severe clinically (P, ≤0.05) and postmortem (P, ≤0.001) when M. hyorhinis CFU were more numerous in synovial fluid (SF) of H pigs than of L pigs (P, ≤0.03). In H pigs but not L pigs, CFU and lesion scores were correlated positively. In H pigs, infection increased the frequency of expression of mRNAs for interleukin-8 (IL-8), IL-10, and tumor necrosis factor alpha (TNF-α) in mononuclear cells from synovial membranes (SM). In L pigs, IL-1α, IL-6, IL-10, and TNF-α mRNAs were increased in frequency of expression. The quantity of the cytokine message for IL-6 was increased in infected H pigs. For L pigs, infection increased the cytokine message for IL-1α, IL-6, IL-10, and TNF-α. IL-6 in SM and gamma interferon (IFN-γ) in SF were produced at a higher copy number in H pigs than in L pigs after infection. For H pigs, there were no positive rank correlations between lesion or CFU scores and cytokines. For L pigs, IL-1α, IL-8, IL-10, and TNF-α in SM correlated with CFU, while IL-6, TNF-β, and IFN-γ in SF correlated with CFU. Lesion score in L pigs correlated with IL-1α in SF. While these results indicate that H and L pigs differ in the cytokine response to M. hyorhinis infection, they do not confirm a characteristic cytokine response in association with the relative susceptibility to infection and arthritis observed in H pigs.

scholarly journals Protection against Cryptococcosis by Using a Murine Gamma Interferon-Producing Cryptococcus neoformans Strain

2007 ◽  
Vol 75 (3) ◽  
pp. 1453-1462 ◽  
Author(s):  
Floyd L. Wormley ◽  
John R. Perfect ◽  
Chad Steele ◽  
Gary M. Cox
Keyword(s):  
Immune Responses ◽  
Cryptococcus Neoformans ◽  
Pulmonary Infection ◽  
Cytokine Expression ◽  
Gamma Interferon ◽  
Host Immunity ◽  
Wild Type ◽  
Novel Method ◽  
Ifn Γ ◽  
Stimulation Of

ABSTRACT We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with a Cryptococcus neoformans strain engineered to produce the Th1-type cytokine gamma interferon (IFN-γ). Mice given a pulmonary infection with an IFN-γ-producing C. neoformans strain were able to resolve the primary infection and demonstrated complete (100%) protection against a second pulmonary challenge with a pathogenic C. neoformans strain. Pulmonary cytokine analyses showed that Th1-type/proinflammatory cytokine and chemokine expression were significantly higher and Th2-type cytokine expression was significantly lower in mice infected with the IFN-γ-producing C. neoformans strain compared to wild-type-infected mice. This increased pulmonary Th1-type cytokine expression was also associated with significantly lower pulmonary fungal burden and significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice infected with the IFN-γ-producing C. neoformans strain compared to wild-type-infected mice. Our results demonstrate that pulmonary infection of mice with a C. neoformans strain expressing IFN-γ results in the stimulation of local Th1-type anti-cryptococcal CMI responses and the development of protective host immunity against future pulmonary cryptococcal infections. The use of fungi engineered to produce host cytokines is a novel method to study immune responses to infection and may be useful in developing vaccine strategies in humans.

scholarly journals Stimulation of Dendritic Cells via CD40 Enhances Immune Responses to Mycobacterium tuberculosisInfection

2001 ◽  
Vol 69 (4) ◽  
pp. 2456-2461 ◽  
Author(s):  
Caroline Demangel ◽  
Umaimainthan Palendira ◽  
Carl G. Feng ◽  
Andrew W. Heath ◽  
Andrew G. D. Bean ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Interleukin 12 ◽  
Ifn Γ ◽  
Cellular Immune ◽  
Stimulation Of

ABSTRACT The resolution of pulmonary tuberculosis (TB) critically depends on the development of the Th1 type of immune responses, as exemplified by the exacerbation of TB in IL-12-deficient mice. Therefore, vaccination strategies optimizing IL-12 production by antigen-presenting cells (APC) in response to mycobacteria may have enhanced protective efficacy. Since dendritic cells (DC) are the critical APC for activation of CD4+ and CD8+ T cells, we examined whether stimulation of Mycobacterium bovis bacillus Calmette Guérin (BCG)-infected DC via CD40 increased their ability to generate Th1-oriented cellular immune responses. Incubation of DC with an agonistic anti-CD40 antibody activated CD40 signaling in DC, as shown by increased expression of major histocompatibility complex class II and costimulatory molecules, mRNA production for proinflammatory cytokines and interleukin 12 (IL-12) p40. This activation pattern was maintained when DC were stimulated with anti-CD40 antibody and infected with BCG. Importantly, CD40-stimulated BCG-infected DC displayed increased capacity to release bioactive IL-12 and to activate gamma interferon (IFN-γ) producing T cells in vitro. Moreover, when C57BL/6 mice were immunized with these DC and challenged with aerosol Mycobacterium tuberculosis, increased levels of mRNA for IL-12 p40, IL-18, and IFN-γ were present in the draining mediastinal lymph nodes. However, the mycobacterial burden in the lungs was not reduced compared to that in mice immunized with BCG-infected non-CD40-stimulated DC. Therefore, although the manipulation of DC via CD40 is effective for enhancing immune responses to mycobacteria in vivo, additional strategies are required to increase protection against virulent M. tuberculosis infection.

Status of Cytokine and Antigen Presentation Genes in Merkel Cell Carcinoma of the Skin

1998 ◽  
Vol 2 (3) ◽  
pp. 138-141 ◽  
Author(s):  
Istvan Arany ◽  
Stephen K. Tyring
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Neuroendocrine Differentiation ◽  
Molecular Characteristics ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Cdc2 Kinase ◽  
Cell Mediated Immune Response ◽  
Ifn Γ ◽  
Polymerase Chain

Background: Merkel carcinoma (MCC) of the skin is an aggressive form of skin cancer, morphologically demonstrating both epithelial and neuroendocrine properties. However, little is known about its molecular characteristics. Objective: The aims of the study were to explore growth characteristics and immune responses of MCCs at the molecular level. Methods: A reverse transcription-polymerase chain reaction (RT-PCR) technique was employed to study those parameters in biopsies of MCCs and their adjacent areas. Results: Analyzing mRNA levels of various epithelial genes (c- myc, cdc2 kinase, E2F, PCNA, p53, and RB, cytokeratins 5 and 10) we concluded that MCCs express markers of epithelial hyperproliferation together with markers of neuroendocrine differentiation (NSE). On the other hand, there is a lack of cytokines (IL-2, IFN-γ) typical for a specific, T cell-mediated immune response in MCCs. However, several cytokines (e.g., IL-12) are produced that are required for the initial steps of that type of immune response. Conclusion: The epithelial hyperproliferation and impaired local immune responses might contribute to the aggressive behaviour of the tumour.

scholarly journals Baseline and early functional immune response is associated with subsequent clinical outcomes of PD-1 inhibition therapy in metastatic melanoma patients

2021 ◽  
Vol 9 (6) ◽  
pp. e002512
Author(s):  
Alexandre Gérard ◽  
Jerome Doyen ◽  
Marion Cremoni ◽  
Laurent Bailly ◽  
Kevin Zorzi ◽  
...  
Keyword(s):  
Immune Response ◽  
Metastatic Melanoma ◽  
Adaptive Immune Cells ◽  
Healthy Donors ◽  
Cytokine Levels ◽  
Melanoma Patients ◽  
Ifn Γ ◽  
Specific Stimulation ◽  
Stimulation Of

BackgroundDespite significant progress with antiprogrammed cell death protein 1 (PD-1) therapy, a substantial fraction of metastatic melanoma patients show upfront therapy resistance. Biomarkers for outcome are missing and the association of baseline immune function and clinical outcome remains to be determined. We assessed the in vitro nonspecific stimulation of immune response at baseline and during anti-PD-1 therapy for metastatic melanoma.MethodsPreviously untreated metastatic melanoma patients received nivolumab and radiotherapy as part of the multicentric phase II trial NIRVANA (NCT02799901). The levels of Th1, Th2 and Th17 cytokines on in vitro non-specific stimulation of innate and adaptive immune cells were measured in patient sera before treatment, and at week 2 and week 6 after the beginning of the treatment, and correlated with tumorous response, progression-free survival (PFS) and occurrence of immune-related adverse events (irAEs). The results in melanoma patients were compared with those of a cohort of 9 sex and age-matched healthy donors.ResultsSeventeen patients were enrolled in this ancillary study. Median follow-up was 16 months (2.2–28.4). The 12-month PFS rate was 67.7%. The incidence of irAEs of any grade was 58.8%. Without in vitro stimulation no differences in cytokines levels were observed between responders and non-responders. On in vitro stimulation, metastatic patients had lower Th1 cytokine levels than healthy donors at baseline for tumor necrosis factor-α and interferon-γ (IFN-γ) (1136 pg/mL vs 5558 pg/mL, p<0.0001; and 3894 pg/mL vs 17 129 pg/mL, p=0.02, respectively). Responders exhibited increasing cytokine levels from baseline to week 6. Non-responders had lower interleukin 17A (IL-17A) levels at baseline than responders (7 pg/mL vs 32 pg/mL, p=0.03), and lower IFN-γ levels at week 6 (3.3 ng/mL vs 14.5 ng/mL, p=0.03). A lower level of IL-17A at week 2 and a lower level of IFN-γ at week 6 correlated with worse PFS (p=0.04 and p=0.04 respectively). At baseline, patients who developed irAEs had higher IL-6 levels (19.3 ng/mL vs 9.2 ng/mL, p=0.03) and higher IL-17A levels (52.5 pg/mL vs 2.5 pg/mL, p=0.009) than those without irAEs.ConclusionsOur findings indicate that cytokine levels after in vitro non-specific stimulation could be a promising biomarker to predict the outcome of PD-1 inhibition therapy.

scholarly journals Protective immunity of recombinant LipL21 and I-LipL21 against Leptospira interrogans serovar Autumnalis N2 infection

2018 ◽  
Vol 12 (01) ◽  
pp. 022-030 ◽  
Author(s):  
Anita Kumari ◽  
Mallela Martha Premlatha ◽  
Veerapandian Raja ◽  
Charles Solomon Akino Mercy ◽  
Kalimuthusamy Sumathi ◽  
...  
Keyword(s):  
Recombinant Proteins ◽  
Protective Immunity ◽  
Laboratory Diagnosis ◽  
Mice Model ◽  
Control Groups ◽  
Cell Mediated Immune Response ◽  
Cytokine Levels ◽  
Ifn Γ ◽  
Antibody Levels ◽  
Stimulation Of

Introduction: Leptospirosis is a zoonotic disease caused by the spirochete of genus Leptospira with widespread distribution in tropical, subtropical and temperate zones. Leptospirosis is often confused with other febrile illnesses including jaundice, dengue, and malaria. Generally, the disease is often underdiagnosed or misdiagnosed. Though leptospirosis is curable with antibiotic treatment, the laboratory diagnosis of the disease is specialized and open to interpretation with multiple kits available to detect the different serological markers of Leptospira. Moreover, when leptospirosis is misdiagnosed, the disease can lead to multi-organ failure and may have fatal effects. There is a need for strategies to develop vaccines and prevent leptospirosis. In the present study, the immunogenic potential of leptospiral recombinant protein LipL21 (rLipL21) and its truncated form I-LipL21 (rI-LipL21) was evaluated. Methodology: The recombinant proteins were established in cyclophosphamide treated BALB/c mice model infected with L. interrogans serovar Autumnalis strain N2. Results: The vaccination study showed 66% and 83% survivability among mice immunized with rLipL21 and rI-LipL21 respectively and post-challenge with leptospiral strain N2 compared to control groups that showed 100% lethality. Additionally, a significant increase in antibody levels and cytokine levels (TNF-a, IFN-γ and IL-10) was observed evidencing a marked stimulation of both humoral and cell-mediated immune response in mice immunized with rLipL21/rI-LipL21 compared to whole cell leptospiral lysate (WCL). Conclusions: This study evidenced protective immunization against leptospirosis with rLipL21 and rI-LipL21 recombinant proteins and are potential candidates for the development of leptospiral vaccine.

Galectin-9 ameliorates anti-GBM glomerulonephritis by inhibiting Th1 and Th17 immune responses in mice

2014 ◽  
Vol 306 (8) ◽  
pp. F822-F832 ◽  
Author(s):  
Qian Zhang ◽  
Hong Luan ◽  
Le Wang ◽  
Fan He ◽  
Huan Zhou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Th17 Cells ◽  
Protective Role ◽  
Blood Levels ◽  
Th2 Cell ◽  
Cell Mediated Immune Response ◽  
Ifn Γ ◽  
Th2 Immunity ◽  
Renal Tubular

Antiglomerular basement membrane glomerulonephritis (anti-GBM GN) is a Th1- and Th17-predominant autoimmune disease. Galectin-9 (Gal-9), identified as the ligand of Tim-3, functions in diverse biological processes and leads to the apoptosis of CD4+Tim-3+ T cells. It is still unclear how Gal-9 regulates the functions of Th1 and Th17 cells and prevents renal injury in anti-GBM GN. In this study, Gal-9 was administered to anti-GBM GN mice for 7 days. We found that Gal-9 retarded the increase of Scr, ameliorated renal tubular injury, and reduced the formation of crescents. The infiltration of Th1 and Th17 cells into the spleen and kidneys significantly decreased in Gal-9-treated nephritic mice. The reduced infiltration of Th1 and Th17 cells might be associated with the downregulation of CCL-20, CXCL-9, and CXCL-10 mRNAs in the kidney. In parallel, the blood levels of IFN-γ and IL-17A declined in Gal-9-treated nephritic mice at days 21 and 28. In addition, an enhanced Th2 cell-mediated immune response was observed in the kidneys of nephritic mice after a 7-day injection of Gal-9. In conclusion, the protective role of Gal-9 in anti-GBM GN is associated with the inhibition of Th1 and Th17 cell-mediated immune responses and enhanced Th2 immunity in the kidney.

Sign in / Sign up

Export Citation Format

Share Document