Bacillus Subtilis Spores as Delivery System for Nasal Plasmodium Falciparum Circumsporozoite Surface Protein Immunization in a Murine Model

Abstract Malaria remains a widespread public health problem in tropical and subtropical regions around the world, and there is still no vaccine available for full protection. In recent years, it has been observed that spores of Bacillus subtillis can act as a vaccine carrier and adjuvant, promoting an elevated humoral response after co-administration with antigens either coupled or integrated to their surface. In our study, B. subtillis spores from the KO7 strain were used to couple the recombinant CSP protein of P. falciparum (rPfCSP), and the nasal humoral-induced immune response in Balb/C mice was evaluated. Our results demonstrate that the spores coupled to rPfCSP increase the immunogenicity of the antigen, which induces high levels of serum IgG, and with balanced Th1/Th2 immune response, being detected antibodies in serum samples for 250 days. Therefore, the use of B. subtilis spores appears to be promising for use as an adjuvant in a vaccine formulation.

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A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

Cellular and Molecular Immunology ◽

10.1038/s41423-020-00588-2 ◽

2021 ◽

Author(s):

Vincent Legros ◽

Solène Denolly ◽

Manon Vogrig ◽

Bertrand Boson ◽

Eglantine Siret ◽

...

Keyword(s):

Intensive Care ◽

Neutralizing Antibodies ◽

Vaccine Development ◽

Surface Protein ◽

Humoral Response ◽

Neutralizing Antibody ◽

Rapid Decline ◽

Serum Samples ◽

Immune Correlates ◽

Human Coronaviruses

AbstractUnderstanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

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Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients

Journal of Clinical Medicine ◽

10.3390/jcm10215153 ◽

2021 ◽

Vol 10 (21) ◽

pp. 5153

Author(s):

Seyedesomaye Jasemi ◽

Gian Luca Erre ◽

Maria Luisa Cadoni ◽

Marco Bo ◽

Leonardo A. Sechi

Keyword(s):

Rheumatoid Arthritis ◽

Immune Response ◽

Humoral Immune Response ◽

Humoral Response ◽

Human Endogenous Retrovirus ◽

Serum Samples ◽

Humoral Immune ◽

Bivariate Correlation ◽

Microbial Biomarkers ◽

Significant Difference

Background/Objective: Chronic humoral immune response against multiple microbial antigens may play a crucial role in the etiopathogenesis of rheumatoid arthritis (RA). We aimed to assess the prevalence and magnitude of antibody response against various bacterial and viral immunogen peptides in the sera of RA patients compared with the general population. Methods: Polyclonal IgG antibodies (Abs) specific for peptides derived from Porphyromonas gingivalis (RgpA, Kpg), Aggregatibacter actinomycetemcomitans (LtxA1, LtxA2), Mycobacterium avium subsp. paratuberculosis (MAP4027), Epstein–Barr virus (EBNA1, EBVBOLF), and human endogenous retrovirus (HERV-W env-su) were detected by ELISA in serum samples from 148 consecutive RA patients and 148 sex and age-matched healthy controls (HCs). In addition, the presence of a relationship between the positivity and the titer of antibodies and RA descriptors was explored by bivariate correlation analysis. Results: RA patients exhibit a higher prevalence of humoral immune response against all tested peptides compared to HCs with a statically significant difference for MAP4027 (30.4% vs. 10.1%), BOLF (25.7% vs. 8.1%), RgpA (24.3% vs. 9.4%), HERV W-env (20.3% vs. 9.4%), and EBNA1 (18.9% vs. 9.4%) peptides. Fifty-three (35.8%) out of 148 RA serum and 93 (62.8%) out of 148 HCs were negative for all pathogen-derived peptides. There was a significant correlation between OD values obtained by ELISA test against all peptides (p < 0.0001). We also found an increased titer and prevalence of Abs against LtxA1 and LtxA2 in seropositive vs. seronegative RF (p = 0.019, p = 0.018). Conclusion: This study demonstrates a significantly increased humoral response against multiple pathogens in patients with RA and implies that they could be an important factor in the pathogenesis of the disease. Therefore, the role of each individual pathogen in RA needs to be further investigated.

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B Cells Over-Activation by Viral Proteins <70 kDa Causes Th2 Immune Suppression in COVID-19 Sepsis

10.20944/preprints202005.0244.v1 ◽

2020 ◽

Author(s):

Javier Martín

Keyword(s):

Immune Response ◽

B Cells ◽

B Cell ◽

Humoral Response ◽

Viral Proteins ◽

Cell Receptor ◽

B Cell Receptor ◽

Th1 Response ◽

Th2 Immune Response ◽

Infected Cells

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

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Endogenous Antibody Responses to SARS-CoV-2 in Patients With Mild or Moderate COVID-19 Who Received Bamlanivimab Alone or Bamlanivimab and Etesevimab Together

Frontiers in Immunology ◽

10.3389/fimmu.2021.790469 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lin Zhang ◽

Josh Poorbaugh ◽

Michael Dougan ◽

Peter Chen ◽

Robert L. Gottlieb ◽

...

Keyword(s):

Immune Response ◽

Viral Load ◽

Humoral Response ◽

Serum Samples ◽

Minimal Impact ◽

Neutralizing Activity ◽

Load Following ◽

Endogenous Immune Response ◽

Antibody Titers ◽

Protein Variants

BackgroundNeutralizing monoclonal antibodies (mAbs) to SARS-CoV-2 are clinically efficacious when administered early, decreasing hospitalization and mortality in patients with mild or moderate COVID-19. We investigated the effects of receiving mAbs (bamlanivimab alone and bamlanivimab and etesevimab together) after SARS-CoV-2 infection on the endogenous immune response.MethodsLongitudinal serum samples were collected from patients with mild or moderate COVID-19 in the BLAZE-1 trial who received placebo (n=153), bamlanivimab alone [700 mg (n=100), 2800 mg (n=106), or 7000 mg (n=98)], or bamlanivimab (2800 mg) and etesevimab (2800 mg) together (n=111). A multiplex Luminex serology assay measured antibody titers against SARS-CoV-2 antigens, including SARS-CoV-2 protein variants that evade bamlanivimab or etesevimab binding, and SARS-CoV-2 pseudovirus neutralization assays were performed.ResultsThe antibody response in patients who received placebo or mAbs had a broad specificity. Titer change from baseline against a receptor-binding domain mutant (Spike-RBD E484Q), as well as N-terminal domain (Spike-NTD) and nucleocapsid protein (NCP) epitopes were 1.4 to 4.1 fold lower at day 15-85 in mAb recipients compared with placebo. Neutralizing activity of day 29 sera from bamlanivimab monotherapy cohorts against both spike E484Q and beta variant (B.1.351) were slightly reduced compared with placebo (by a factor of 3.1, p=0.001, and 2.9, p=0.002, respectively). Early viral load correlated with the subsequent antibody titers of the native, unmodified humoral response (p<0.0001 at Day 15, 29, 60 and 85 for full-length spike).ConclusionsPatients with mild or moderate COVID-19 treated with mAbs develop a wide breadth of antigenic responses to SARS-CoV-2. Small reductions in titers and neutralizing activity, potentially due to a decrease in viral load following mAb treatment, suggest minimal impact of mAb treatment on the endogenous immune response.

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Influence of Echinococcus multilocularis infection on immune response of mice and their offspring

Helminthologia ◽

10.2478/s11687-011-0034-2 ◽

2011 ◽

Vol 48 (4) ◽

pp. 244-250

Author(s):

K. Reiterová ◽

D. Antolová

Keyword(s):

Immune Response ◽

T Cell ◽

Echinococcus Multilocularis ◽

Parasitic Infection ◽

Humoral Response ◽

Late Pregnancy ◽

Th2 Immune Response ◽

Group 2 ◽

T Cell Subpopulations ◽

Group 1

AbstractParasitic infection during pregnancy represents a serious stress factor and affects the course of pregnancy and the foeto-maternal relationship. The infection may not clinically manifest itself, however it can modulate the immune response of the offspring for a long-time. The influence of secondary Echinococcus multilocularis infection on the proportion of CD4+ and CD8+ T cells and the level of anti-Echinococcus antibodies were studied in Balb/c mice. The female mice were infected with homogenised metacestode material containing 2000 E. multilocularis protoscoleces (Group 1, 2). Group 1 was fertilised on day 60 post infection, while Group 2 remained unfertilised. Group 3 was uninfected and fertilised on the same day as Group 1. The numbers of both T cell subpopulations were higher in non-pregnant than in pregnant mice. In late pregnancy, the decline of CD4+, however, the increase of CD8+ T-cell subtypes were observed in both, infected and uninfected mothers, respectively. The strong humoral response with the high production of IgM and IgG2b antibodies in infected mice was detected. In infected mothers, IgG2b level was higher than in infected nonpregnant mice during almost whole monitored period. In Group 1, delivery caused suppression of Th2 immune response, represented by IgG1, under the level observed in uninfected mothers. The findings show the changes in helper regulatory and cytotoxic immunity mechanisms of infected mothers. In offspring of infected mothers all IgG subclasses were detected, however specific IgM were not transmitted neither transplacentary, nor transmammary.

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Electrolyzed Oxidizing Water Modulates the Immune Response in BALB/c Mice Experimentally Infected with Trypanosoma cruzi

Pathogens ◽

10.3390/pathogens9110974 ◽

2020 ◽

Vol 9 (11) ◽

pp. 974

Author(s):

Olivia Rodríguez-Morales ◽

Juan José Cabrera-Mata ◽

Silvia del C. Carrillo-Sánchez ◽

Rodolfo A. Gutiérrez-Ocejo ◽

Lidia Baylón-Pacheco ◽

...

Keyword(s):

Immune Response ◽

Trypanosoma Cruzi ◽

Acute Phase ◽

Public Health Problem ◽

Fold Increase ◽

Health Condition ◽

Major Public Health Problem ◽

Ifn Gamma ◽

Th2 Immune Response ◽

General Physical

Chagas disease is a major public health problem in Latin America. The mixed Th1/Th2 immune response is required against Trypanosoma cruzi. Electrolyzed oxidizing water (EOW) has been shown to have germicidal efficacy. The objective of this study was to evaluate the EOW effectiveness in T. cruzi-infected BALB/c mice clinically, immunologically, and histologically. The severity of the infection was assessed by parasitaemia, general health condition, mortality, mega syndromes, and histological lesions. IgG, TNF-alpha, IFN-gamma, and IL-1 beta levels were quantified. The EOW administration showed a beneficial effect on parasitaemia, general physical condition, and mortality. High levels of IgG1 at 50 days postinfection were observed. Prophylactic EOW treatment was able to induce a predominantly TH1 immune response based on an IgG2a levels increase at the late acute phase, and a 10-fold increase of IFN-gamma in whole acute phase. EOW was able to control the acute phase infection as effectively as benznidazole. Splenomegaly was caused by EOW treatment and lymphadenopathy was stimulated by T. cruzi infection in all groups. Severe tissue damage was not prevented by EOW treatments. Moderate efficacy may be due to immunomodulatory properties and not to a direct toxic effect on the parasite.

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Immunization with native surface protein NcSRS2 induces a Th2 immune response and reduces congenital Neospora caninum transmission in mice

International Journal for Parasitology ◽

10.1016/j.ijpara.2005.05.013 ◽

2005 ◽

Vol 35 (13) ◽

pp. 1407-1415 ◽

Cited By ~ 48

Author(s):

G.J. Haldorson ◽

B.A. Mathison ◽

K. Wenberg ◽

P.A. Conrad ◽

J.P. Dubey ◽

...

Keyword(s):

Immune Response ◽

Neospora Caninum ◽

Surface Protein ◽

Th2 Immune Response ◽

Native Surface

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PO 8571 CYTOKINE PROFILE IN ASYMPTOMATIC SCHOOL CHILDREN CO-INFECTED WITH HELMINTHS AND PLASMODIUM FALCIPARUM IN IBADAN, SOUTH-WEST NIGERIA

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.145 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A55.2-A55

Author(s):

George Ademowo ◽

Olawunmi Rabiu ◽

Ganiyu Arinola ◽

Catherine O Falade

Keyword(s):

Immune Response ◽

School Children ◽

Infected Group ◽

Single Infection ◽

Serum Samples ◽

Th2 Immune Response ◽

Tnf Α ◽

Insignificant Difference ◽

Ifn Γ ◽

The Tropics

BackgroundIntestinal helminths and malaria are among the most prevalent infectious diseases in the tropics. The effect of co-infections on immune response is not clearly understood. We therefore investigated the immune response profile in children with and without symptoms.MethodsA total of 78 afebrile school children (20 helminth/malaria-co-infected, 17 helminth-infected, 19 malaria-infected and 22 uninfected) and 75 febrile children (14 helminth/malaria-co-infected, 16 helminth-infected, 20 malaria-infected and 25 uninfected) were recruited into the study. Helminths were screened using Kato Katz method while malaria parasite screening was done using Giemsa-stained thick blood films. Circulating TNF-α, IFN-γ, IL-1, IL-10 and IL-6 concentrations were assessed by ELISA from serum samples. Data were analysed using analysis of variance.ResultsAmong the afebrile school children, IL-10 was significantly increased in helminth-infected children compared with helminth/malaria-co-infected, malaria-infected and uninfected groups (p<0.05). IFN-γ was significantly elevated in malaria and malaria/helminth-co-infection relative to helminth alone (p<0.05). IL-1 level was significantly higher in single infection of helminth and malaria relative to co-infection and the uninfected groups (p<0.05). An insignificant difference was observed for IL-6 and TNF-α concentrations across all the four groups while among febrile children. IL-6 was significantly increased among helminth alone and helminth/malaria-co-infection relative to malaria-infected group (p<0.05). IL-10 was significantly elevated in co-infected group compared with helminth- or malaria-infected group while TNF-α was significantly increased in helminth and helminth-malaria co-infection compared with uninfected or malaria-infected group (p<0.05). IFN-γ level was insignificant in the infection groups relative to uninfected group (p<0.05); IL-1 level similar across the groups.ConclusionHelminth infection seems to upregulate the Th2 immune response among children with symptomatic uncomplicated malaria while there were no significant changes in Th immune response among afebrile children.

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