Lymphatic filariasis-specific immune responses in relation to lymphoedema grade and infection status. I. Cellular responses

AbstractAlthough multiple vaccine strategy for lymphatic filariasis has provided tremendous hope, the choice of antigens used in combination has determined its success in the previous studies. Multiple antigens comprising key vaccine candidates from different life cycle stages would provide a promising strategy if the antigenic combination is chosen by careful screening. In order to analyze one such combination, we have used a chimeric construct carrying the well studied B. malayi antigens thioredoxin (BmTRX) and venom allergen homologue (BmVAH) as a fusion protein (TV) and evaluated its immune responses in mice model. The efficacy of fusion protein vaccine was explored in comparison with the single antigen vaccines and their cocktail. In mice, TV induced significantly high antibody titer of 1,28,000 compared to cocktail vaccine TRX+VAH (50,000) and single antigen vaccine TRX (16,000) or VAH (50,000). Furthermore, TV elicited higher level of cellular proliferative response together with elevated levels of IFN-γ, IL-4 and IL-5 indicating a Th1/Th2 balanced response. The isotype antibody profile showed significantly high level of IgG1 and IgG2b confirming the balanced response elicited by TV. Immunization with TV antigen induced high levels of both humoral and cellular immune responses compared to either cocktail or antigen given alone. The result suggests that TV is highly immunogenic in mice and hence the combination needs to be evaluated for its prophylactic potential.

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The Wellcome Trust Lecture: Infection and disease in lymphatic filariasis: an immunological perspective

Parasitology ◽

10.1017/s0031182000075259 ◽

1992 ◽

Vol 104 (S1) ◽

pp. S71-S79 ◽

Cited By ~ 128

Author(s):

E. A. OtteSen

Keyword(s):

Immune Responses ◽

Lymphatic Filariasis ◽

Clinical Manifestations ◽

Genetic Determination ◽

Inflammatory Reactions ◽

Alternative Pathways ◽

Immunodeficient Mice ◽

Parasite Antigen ◽

Immunological Responses ◽

Asymptomatic Patients

SUMMARYThe basic tenet of the immunological perspective of fuiarial disease is that differential immune responsiveness among individuals exposed to infection results in the different clinical manifestations that develop. The mechanisms involved in this differential responsiveness appear to reflect different T-cell cytokine response patterns. Asymptomatic patients with the clinically silent presentation of ‘asymptomatic microfilaraemia’, who have been previously described as being ‘immunosuppressed’ with respect to their generating pro-inflammatory (Th1-type) immune responses to parasite antigen, are now recognized to be fully responsive to parasite antigen but to produce cytokines and mediators that have primarily anti-inflammatory (Th2-like) effects. Studies with immunodeficient mice have indicated the existence of two alternative pathways to the development of lymphatic pathology: one dependent on the induction of inflammatory reactions by the host immune response, the other entirely independent of the immune system and reflecting the direct actions of the parasite or its products on the lymphatics. As histopathology of affected human lymphatics is consistent with this hypothesis, it may be that the lymphatic pathology seen normally in the amicrofilaraemic, highly immunoresponsive infected patients derives from inflammation induced by immune responses to parasite antigen, whereas the lymphatic pathology sometimes seen coexisting with the ‘immunosuppressed’ state of asymptomatic microfilaraemia actually reflects lymphatic damage that is not immunologically mediated. Though little information exists about the ‘natural history’ of lymphatic filariasis, there is no evidence for an inevitable progression from one clinical form to another. Instead, there appears to be a definite plasticity in the response that depends on prior (? pre-natal) and current exposure to the parasite as well as on the immunomodulatory effects it induces. This plasticity does not appear to be complete, however, as there is no evidence that a chronically infected host who has developed strong pro-inflammatory immune responses can subsequently become sufficiently ‘down-regulated’ to support an asymptomatic microfilaraemia type of infection. Another possible constraint to the plasticity of the clinical and immunological responses may be the genetic determination of certain unusual syndromes, such as tropical pulmonary eosinophilia or TPE, though this hypothesis remains to be proven.

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Adenine nucleotides as paracrine mediators and intracellular second messengers in immunity and inflammation

Biochemical Society Transactions ◽

10.1042/bst20180419 ◽

2019 ◽

Vol 47 (1) ◽

pp. 329-337 ◽

Cited By ~ 2

Author(s):

Ralf Fliegert ◽

Jörg Heeren ◽

Friedrich Koch-Nolte ◽

Viacheslav O. Nikolaev ◽

Christian Lohr ◽

...

Keyword(s):

Immune System ◽

T Lymphocytes ◽

Immune Responses ◽

Nicotinamide Adenine Dinucleotide ◽

Adenine Nucleotides ◽

Second Messengers ◽

Cellular Responses ◽

Fine Tuning ◽

Inflammatory Processes ◽

Intracellular Second Messengers

Abstract Adenine nucleotides (AdNs) play important roles in immunity and inflammation. Extracellular AdNs, such as adenosine triphosphate (ATP) or nicotinamide adenine dinucleotide (NAD) and their metabolites, act as paracrine messengers by fine-tuning both pro- and anti-inflammatory processes. Moreover, intracellular AdNs derived from ATP or NAD play important roles in many cells of the immune system, including T lymphocytes, macrophages, neutrophils and others. These intracellular AdNs are signaling molecules that transduce incoming signals into meaningful cellular responses, e.g. activation of immune responses against pathogens.

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New activity of yamamarin, an insect pentapeptide, on immune system of mealworm,Tenebrio molitor

Bulletin of Entomological Research ◽

10.1017/s0007485317000839 ◽

2017 ◽

Vol 108 (3) ◽

pp. 351-359 ◽

Cited By ~ 2

Author(s):

K. Walkowiak-Nowicka ◽

G. Nowicki ◽

M. Kuczer ◽

G. Rosiński

Keyword(s):

Immune System ◽

Immune Responses ◽

Cellular Responses ◽

Tenebrio Molitor ◽

Immunotropic Activity ◽

Silk Moth ◽

Wide Range ◽

Selected Functions ◽

Active Substances ◽

Stimulation Of

AbstractIn insects, two types of the immune responses, cellular and humoral, constitute a defensive barrier against various parasites and pathogens. In response to pathogens, insects produce a wide range of immune agents that act on pathogens directly, such as cecropins or lysozyme, or indirectly by the stimulation of hemocyte migration or by increasing phenoloxidase (PO) activity. Recently, many new immunologically active substances from insects, such as peptides and polypeptides, have been identified. Nevertheless, in the most cases, their physiological functions are not fully known. One such substance is yamamarin – a pentapeptide isolated from the silk mothAntheraea yamamai. This yamamarin possesses strong antiproliferative properties and is probably involved in diapause regulation. Here, we examined the immunotropic activity of yamamarin by testing its impact on selected functions of the immune system in heterologous bioassays with the beetleTenebrio molitor, commonly known as a stored grains pest. Our results indicate that the pentapeptide affects the activity of immune processes in the beetle. We show that yamamarin induces changes in both humoral and cellular responses. The yamamarin increases the activity of PO, as well as causes changes in the hemocyte cytoskeleton and stimulates phagocytic activity. We detected an increased number of apoptotic hemocytes, however after the yamamarin injection, no significant variations in the antibacterial activity in the hemolymph were observed. The obtained data suggest that yamamarin could be an important controller of the immune system inT. molitor.

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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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Intranasal Vaccination with the Recombinant Listeria monocytogenes ΔactA prfA*Mutant Elicits Robust Systemic and Pulmonary Cellular Responses and Secretory Mucosal IgA

Clinical and Vaccine Immunology ◽

10.1128/cvi.00254-10 ◽

2011 ◽

Vol 18 (4) ◽

pp. 640-646 ◽

Cited By ~ 14

Author(s):

Jin Qiu ◽

Lin Yan ◽

Jianbo Chen ◽

Crystal Y. Chen ◽

Ling Shen ◽

...

Keyword(s):

Listeria Monocytogenes ◽

Immune Responses ◽

Cellular Response ◽

Cellular Responses ◽

Broth Culture ◽

Intravenous Route ◽

Content Type ◽

Vaccine Candidates ◽

Ifn Γ ◽

Subcutaneous Immunization

ABSTRACTWe previously showed that recombinant (r)Listeria monocytogenescarrying ΔactAand a selectedprfA*mutation (r-ListeriaΔactA prfA*) secreted >100-fold more immunogen in broth culture than wild-type r-Listeriaor r-ListeriaΔactAand elicited much greater cellular and humoral immune responses than r-ListeriaΔactAafter intravenous vaccination of mice. Here, we conducted comparative studies evaluating vaccine-elicited immune responses in systemic and mucosal sites after intranasal, intravenous, intraperitoneal, or subcutaneous immunization of mice with r-ListeriaΔactA prfA*vaccine candidates. Intranasal vaccination of mice with r-ListeriaΔactA prfA* vaccine candidates elicited a robust gamma interferon-positive (IFN-γ+) cellular response in systemic sites, although intravenous or intraperitoneal immunization was more efficient. Surprisingly, intranasal vaccination elicited an appreciable pulmonary IFN-γ+cellular response that was nonstatistically higher than the magnitude induced by the intravenous route but was significantly greater than that elicited by subcutaneous immunization. Furthermore, although intranasal r-ListeriaΔactA prfA*delivery induced poor systemic IgG responses, intranasal vaccination elicited appreciable secretory immunogen-specific IgA titers that were similar to or higher in mucosal fluid than those induced by subcutaneous and intravenous immunizations. Thus, intranasal vaccination with r-ListeriaΔactA prfA*appears to be a useful approach for eliciting robust systemic and pulmonary cellular responses and measurable secretory mucosal IgA titers.

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Pneumococcal colonization impairs nasal and lung mucosal immune responses to Live Attenuated Influenza Vaccination in adults

10.1101/2020.02.24.20025098 ◽

2020 ◽

Cited By ~ 1

Author(s):

Beatriz F. Carniel ◽

Fernando Marcon ◽

Jamie Rylance ◽

Seher Zaidi ◽

Jesus Reine ◽

...

Keyword(s):

Influenza Virus ◽

Immune Responses ◽

Influenza Vaccination ◽

Cellular Responses ◽

Antibody Responses ◽

Virus Infections ◽

Mucosal Antibody ◽

Pneumococcal Colonization ◽

Differential Immunity ◽

Nasal Microbiota

ABSTRACTInfluenza virus infections affect millions of people annually. Current available vaccines provide varying rates of protection. There is a knowledge gap on how the nasal microbiota, particularly established pneumococcal colonization, shapes the response to influenza vaccination. In this study, we inoculated healthy adults with live S. pneumoniae and vaccinated them three days later with either TIV or LAIV. Vaccine-induced immune responses were assessed in nose, blood and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, pre-existing pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared to either TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. This important confounder should be considered when assessing LAIV efficacy.

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Differential Immunogenicity of BNT162b2 or ChAdOx1 Vaccines After Extended-Interval Homologous Dual Vaccination in Older People

10.21203/rs.3.rs-727799/v1 ◽

2021 ◽

Author(s):

Helen Parry ◽

Rachel Bruton ◽

Christine Stephens ◽

Kevin Brown ◽

Gayatri Amirthalingam ◽

...

Keyword(s):

Immune Responses ◽

Older People ◽

Natural Infection ◽

Cellular Responses ◽

Antibody Responses ◽

Vaccine Responses ◽

Cell Responses ◽

Boost Vaccine ◽

The Uk ◽

Cellular Immune

Abstract BackgroundSeveral SARS-CoV-2 vaccines have shown clinical efficacy against Covid-19 infection but there remains uncertainty about the immune responses elicited by different regimens. This is a particularly important question for older people who are at increased clinical risk following infection and in whom immune senescence may limit vaccine responses. The BNT162b2 mRNA and ChAdOx1 adenovirus vaccines were the first two vaccines deployed in the UK programme using an 8-12 week ‘extended interval’.ObjectivesWe undertook analysis of the spike-specific antibody and cellular immune response in 131 participants aged 80+ years after the second dose of ‘extended interval’ dual vaccination with either BNT162b2 mRNA (n=54) or ChAdOx1 (n=77) adenovirus vaccine. Blood samples were taken 2-3 weeks after second vaccine and were paired with samples taken at 5-weeks after first vaccine which have been reported previously. Antibody responses were measured using the Elecsys® electrochemiluminescence immunoassay assay and cellular responses were assessed by IFN-g ELISpot. ResultsAntibody responses against spike protein became detectable in all donors following dual vaccination with either vaccine. 4 donors had evidence of previous natural infection which is known to boost vaccine responses. Within the 53 infection-naïve donors the median antibody titre was 4030 U/ml (IQR 1892-8530) following BNT162b2 dual vaccination and 1405 (IQR 469.5- 2543) in the 74 patients after the ChAdOx1 vaccine (p=<0.0001). Spike-specific T cell responses were observed in 30% and 49% of mRNA and ChAdOx1 recipients respectively and median responses were 1.4-times higher in ChAdOx1 vaccinees at 14 vs 20 spots/million respectively (p=0.022).ConclusionDual vaccination with BNT162b2 or ChAdOx1 induces strong humoral immunity in older people following an extended interval protocol. Antibody responses are 2.9-times higher following the mRNA regimen whilst cellular responses are 1.7-times higher with the adenovirus-based vaccine. Differential patterns of immunogenicity are therefore elicited from the two vaccine platforms. It will be of interest to assess the relative stability of immune responses after these homologous vaccine regimens in order to assess the potential need for vaccine boosting. Furthermore, these findings indicate that heterologous vaccine platforms may offer the opportunity to further optimize vaccine responses.

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