scholarly journals Cellular and humoral immunogenicity of a SARS-CoV-2 mRNA vaccine in patients on hemodialysis

2021 ◽  
Author(s):  
Monika Strengert ◽  
Matthias Becker ◽  
Gema Morilla Ramos ◽  
Alex Dulovic ◽  
Jens Gruber ◽  
...  
Keyword(s):  
At Risk ◽  
Immune Responses ◽  
Binding Capacity ◽  
Interferon Γ ◽  
Intermittent Hemodialysis ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Humoral Immune Responses ◽  
Increased Risk ◽  
Cellular Immune

Abstract Background Patients with chronic renal insufficiency on intermittent hemodialysis face an increased risk of COVID-19 induced mortality and impaired vaccine responses. To date, only few studies addressed SARS-CoV-2 vaccine elicited immunity in this immunocompromised population. Methods We assessed immunogenicity of the mRNA vaccine BNT162b2 in at risk dialysis patients and characterized systemic cellular and humoral immune responses in serum and saliva using interferon γ release assay and multiplex-based cytokine and immunoglobulin measurements. We further compared binding capacity and neutralization efficacy of vaccination-induced immunoglobulins against emerging SARS-CoV-2 variants of concern B.1.1.7, B.1.351, B.1.429 and Cluster 5 by ACE2-RBD competition assay. Findings Patients on intermittent hemodialysis exhibit detectable but variable cellular and humoral immune responses against SARS-CoV-2 and variants of concern after a two-dose regimen of BNT162b2. Although vaccination-induced immunoglobulins were detectable in saliva and plasma, both anti-SARS-CoV-2 IgG and neutralization efficacy was reduced compared to controls. Similarly, T-cell mediated interferon γ release after stimulation with SARS-CoV-2 spike peptides was significantly diminished. Interpretation Quantifiable humoral and cellular immune responses after BNT162b2 vaccination in individuals on intermittent dialysis are encouraging, but urge for longitudinal follow-up to assess longevity of immunity. Diminished virus neutralization and interferon γ responses in face of emerging variants of concern may favor this at risk population for re-vaccination using modified vaccines at the earliest opportunity.

scholarly journals mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Helen Parry ◽  
Gokhan Tut ◽  
Rachel Bruton ◽  
Sian Faustini ◽  
Christine Stephens ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Antibody Responses ◽  
Vaccine Platform ◽  
Humoral Immune ◽  
Vaccine Responses ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

scholarly journals EFFECT OF BACILLUS OF CALMETTE-GUÉRIN, AVRIDINE AND Propionibacterium acnes AS IMMUNOMODULATORS ON RABIES IN MICE

1999 ◽  
Vol 41 (2) ◽  
pp. 107-114 ◽  
Author(s):  
J. MEGID ◽  
M.T.S. PERAÇOLI ◽  
P.R. CURI ◽  
C.R. ZANETTI ◽  
W.H. CABRERA ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Cellular Immune Response ◽  
Propionibacterium Acnes ◽  
Inoculation Test ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cellular Immune

The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment. Lower levels of interferon-<FONT FACE="Symbol">g</font> (IFN-<FONT FACE="Symbol">g</font>) were found in infected mice. The intra-pad inoculation test (IPI) was not effective to detect cellular immune response, contrary to the results found in MIF reaction. The survival of mice did not present correlation with the levels of antirabies serum neutralizing (SN) antibodies titers, IFN-<FONT FACE="Symbol">g</font> concentration and MIF response.

scholarly journals Host JAK/Stat activity is a target of endoparasitoid wasp virulence strategies

2018 ◽  
Author(s):  
Susanna E. Brantley ◽  
Nathan T. Mortimer ◽  
Todd A. Schlenke
Keyword(s):  
Immune Responses ◽  
Genetic Model ◽  
Fat Body ◽  
Innate Immune Responses ◽  
Microbial Infection ◽  
Wasp Species ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Stat Signaling ◽  
Cellular Immune

AbstractInnate immune responses depend on the action of multiple conserved signaling pathways. Pathways important for activation of humoral immune responses following microbial infection are well-characterized in the genetic model species Drosophila melanogaster, but our understanding of fly cellular immunity, and how parasites suppress it, is relatively fragmentary. Fly larvae mount a coordinated cellular immune response following infection by endoparasitoid wasps, characterized by the production of specialized blood cells called lamellocytes that form a tight capsule around wasp eggs in their hemolymph. The conserved JAK/Stat signaling pathway has been implicated in lamellocyte proliferation and is required for successful encapsulation of wasp eggs. Here we show that activity of Stat92E, the D. melanogaster Stat ortholog, is induced in the fat body and hemocytes following wasp infection. Virulent wasp species are able to suppress activation of a Stat92E activity reporter during infection, suggesting they target upstream activation of this pathway as part of their virulence strategies. Furthermore, two wasp species (Leptopilina guineaensis and Ganaspis xanthopoda) suppress phenotypes associated with gain-of-function mutations in hopscotch, the D. melanogaster JAK ortholog, showing that they inhibit JAK/Stat activity downstream of JAK. Our data demonstrate that endoparasitoid wasp virulence factors block JAK/Stat signaling to overcome fly immune defenses.

scholarly journals A highly specific assay for the detection of SARS-CoV-2-reactive CD4+ and CD8+ T cells in COVID-19 patients

2020 ◽  
Author(s):  
Henning Zelba ◽  
David Worbs ◽  
Johannes Harter ◽  
Natalia Pieper ◽  
Christina Kyzirakos-Feger ◽  
...  
Keyword(s):  
T Cells ◽  
Membrane Protein ◽  
Immune Responses ◽  
Cd8 T Cells ◽  
Functional Markers ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Gaining detailed insights into the role of host immune responses in viral clearance is critical for understanding COVID-19 pathogenesis and future treatment strategies. While studies analyzing humoral immune responses against SARS-CoV-2 were available rather early during the pandemic, cellular immunity came into focus of investigations just recently. For the present work, we have adapted a protocol, designed for the detection of rare neoantigen-specific Memory T cells in cancer patients for studying cellular immune responses against SARS-CoV-2. Both, CD4+ and CD8+ T cells were detected after 6 days of in vitro expansion using overlapping peptide libraries representing the whole viral protein. The assay readout was an Intracellular cytokine staining and flow cytometric analysis detecting four functional markers simultaneously (CD154, TNF, IL-2, IFN-γ). We were able to detect SARS-CoV-2-specific T cells in 9 of 9 COVID-19 patients with mild symptoms. All patients had reactive T cells against at least one of 12 analyzed viral antigens and all patients had Spike-specific T cells. While some antigens were detected by CD4+ and CD8+ T cells, Membrane protein was mainly recognized by CD4+ T cells. Strikingly, we were not able to detect SARS-CoV-2-specific T cells in 9 unexposed healthy individuals. We are presenting a highly specific protocol for the detection of SARS-CoV-2-reactive T cells. Our data confirmed the important role of cellular immune responses in understanding SARS-CoV-2 clearance. We showed that Spike is the most immunogenic antigen. We have introduced Membrane protein as interesting target for studying humoral immune responses in convalescent COVID-19 patients.

scholarly journals The immune protection induced by a serine protease from the Trichinella spiralis adult against Trichinella spiralis infection in pigs

2021 ◽  
Vol 15 (5) ◽  
pp. e0009408
Author(s):  
Daoxiu Xu ◽  
Xue Bai ◽  
Jing Xu ◽  
Xuelin Wang ◽  
Zijian Dong ◽  
...  
Keyword(s):  
Immune Responses ◽  
Serine Protease ◽  
Trichinella Spiralis ◽  
Flow Cytometric Analysis ◽  
Protease Gene ◽  
Partial Protection ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cellular Immune ◽  
Antibody Levels

Trichinellosis is a major foodborne parasitosis caused by Trichinella spiralis. In the present study, a serine protease gene from an adult T. spiralis (Ts-Adsp) cDNA library was cloned, expressed in Escherichia coli and purified by Ni-affinity chromatography. Previous studies of our laboratory have found that mice vaccinated with recombinant Ts-Adsp protein (rTs-Adsp) exhibited partial protection against T. spiralis infection. In this study, the protective effect of rTs-Adsp against T. spiralis infection in pigs was further explored. The cell-mediated and humoral immune responses induced by rTs-Adsp were measured, including the dynamic trends of specific antibody levels (IgG, IgG1, IgG2a and IgM), as well as the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in the serum. Moreover, the changes in T lymphocytes, B lymphocytes, and neutrophils were measured to evaluate cellular immune responses in pigs vaccinated with rTs-Adsp. The results indicated that a Th1-Th2 mixed immune response with Th1 predominant was induced by rTs-Adsp after vaccination. Flow cytometric analysis showed that the proportions of CD4+ T cells, B cells, and neutrophils in the immunized groups were significantly increased. Furthermore, pigs vaccinated with rTs-Adsp exhibited a 50.9% reduction in the muscle larvae burden, compare with pigs from the PBS group five weeks after challenged. Our results suggested that rTs-Adsp elicited partial protection and it could be a potential target molecule for preventing and controlling Trichinella transmission from pigs to human.

scholarly journals Effects of a multispecies synbiotic on intestinal mucosa immune responses

2019 ◽  
Author(s):  
Alpha Fardah Athiyyah ◽  
Nur Aisiyah Widjaja ◽  
Pramira Fitri ◽  
Ariani Setiowati ◽  
Andy Darma ◽  
...  
Keyword(s):  
Immune Responses ◽  
Intestinal Mucosa ◽  
Immunoglobulin A ◽  
Streptococcus Thermophilus ◽  
Orogastric Tube ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Colony Forming Units ◽  
Cellular Immune

Background and Objectives: Probiotics and prebiotics are known to regulate immune responses. A synbiotic is a product that combines probiotics and prebiotics in a single dosage form. In this study, we attempt to present the effects of a multispe- cies synbiotic on intestinal mucosa immune responses after exposure to Escherichia coli O55:B5 lipopolysaccharide (LPS). Materials and Methods: Totally 21 male Balb/c mice were randomly classified into two groups. The K-I group received LPS and a synbiotic, and the K-II group received LPS alone. The synbiotic was administered for 21 consecutive days, where- as LPS was administered once on the 15th day. Specifically, a synbiotic containing 1 × 109 colony forming units (CFUs) of the probiotic combination of Lactobacillus acidophilus PXN 35, L. casei subsp. casei PXN 37, L. rhamnosus PXN 54, L. bul- garicus PXN 39, Bifidobacterium breve PXN 25, B. infantis PXN 27 and Streptococcus thermophilus PXN 66 and the prebi- otic fructo-oligosaccharide was administered through an orogastric tube. Immunohistochemistry was performed to measure immunoglobulin A (IgA) levels for humoral immune responses and CD4+ and CD8+ levels for cellular immune responses. Results: An independent-samples t-test revealed significant increases of the numbers of IgA- (p = 0.027) and CD4-express- ing cells (p = 0.009) but not the number of CD8-expressing cells in the K-I group compared with those in the K-II group. Conclusion: The multispecies synbiotic had immunoregulatory effects on IgA and CD4 expression in LPS-exposed mice.

scholarly journals ESAT-6 Subunit Vaccination againstMycobacterium tuberculosis

2000 ◽  
Vol 68 (2) ◽  
pp. 791-795 ◽  
Author(s):  
Lise Brandt ◽  
Martin Elhay ◽  
Ida Rosenkrands ◽  
Erik B. Lindblad ◽  
Peter Andersen
Keyword(s):  
Immune Responses ◽  
Lipid A ◽  
T Cell Response ◽  
Cell Mediated Immunity ◽  
Adjuvant Activity ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Monophosphoryl Lipid A ◽  
Cellular Immune

ABSTRACT The ESAT-6 antigen from Mycobacterium tuberculosis is a dominant target for cell-mediated immunity in the early phase of tuberculosis (TB) in TB patients as well as in various animal models. The purpose of our study was to evaluate the potential of ESAT-6 in an experimental TB vaccine. We started out using dimethyl dioctadecylammonium bromide (DDA), an adjuvant which has been demonstrated to be efficient for the induction of cellular immune responses and has been used successfully before as a delivery system for TB vaccines. Here we demonstrate that, whereas immune responses to both short-term-culture filtrate and Ag85B are efficiently induced with DDA, this adjuvant was inefficient for the induction of immune responses to ESAT-6. Therefore, we investigated the modulatory effect of monophosphoryl lipid A (MPL), an immunomodulator which in different combinations has demonstrated strong adjuvant activity for both cellular and humoral immune responses. We show in the present study that vaccination with ESAT-6 delivered in a combination of MPL and DDA elicited a strong ESAT-6-specific T-cell response and protective immunity comparable to that achieved withMycobacterium bovis BCG.

scholarly journals Toxoplasma gondii: humoral and cellular immune response of BALB/c mice immunized via intranasal route with rTgROP2

2010 ◽  
Vol 19 (4) ◽  
pp. 210-216 ◽  
Author(s):  
Michelle Igarashi ◽  
Dauton Luiz Zulpo ◽  
Ivo Alexandre Leme da Cunha ◽  
Luiz Daniel Barros ◽  
Vanessa Figueredo Pereira ◽  
...  
Keyword(s):  
Immune Response ◽  
Recombinant Protein ◽  
Immune Responses ◽  
Stimulation Index ◽  
Intranasal Route ◽  
Iptg Induction ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

TgROP2 is an intracellular protein associated with rhoptries of Toxoplama gondii and an antigen component of a candidate vaccine for toxoplasmosis. The purpose of the present study was to evaluate the efficacy of rTgROP2 to stimulate humoral and cellular immune responses in BALB/c mice via intranasal injection. TgROP2 partial coding sequence was (196-561) amplified by PCR from genomic T. gondii RH strain DNA and cloned into the pTrcHis expression vector. Escherichia coli Rosetta 2 cells transformed with pTrcHis-TgROP2 showed high levels (~1 mg.mL-1) of recombinant protein after 4 hours of IPTG induction. Recombinant TgROP2 exhibited an apparent Mr equal to 54 kDa. In order to test immunogenicity of the recombinant protein, 10 BALB/c mice received 10 µg of rROP2 protein + 10 µg of Quil-A via intranasal injection. Doses were administered at days 0, 21, and 42. Three animals were euthanized and used to evaluate cell-ular immune response on day 62. Five (50%) and two (20%) out of ten animals produced IgG (DO mean = 0.307; cut-off = 0.240) and IgA (DO mean = 0.133, cut-off = 0.101), respectively, by ELISA on day 62. The proliferation of splenocytes revealed high stimulation index (SI) when co-cultured with 5, 10 and 15 µg.mL-1 of rTgROP2. These results indicate that intranasal immunization with recombinant protein ROP2 plus Quil-A can elicit both cellular and humoral immune responses in BALB/c mice.

scholarly journals Oral Vaccination with the Porcine Rotavirus VP4 Outer Capsid Protein Expressed byLactococcus lactisInduces Specific Antibody Production

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Yi-jing Li ◽  
Guang-peng Ma ◽  
Gui-wei Li ◽  
Xin-yuan Qiao ◽  
Jun-wei Ge ◽  
...  
Keyword(s):  
Immune Responses ◽  
Oral Vaccine ◽  
Surface Expression ◽  
Oral Immunization ◽  
Secretory Iga ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Specific Antibody Production ◽  
Cellular Immune ◽  
Porcine Rotavirus

The objective of this study to design a delivery system resistant to the gastrointestinal environment for oral vaccine against porcine rotavirus.Lactococcus lactisNZ9000 was transformed with segments ofvP4of the porcine rotavirus inserted into the pNZ8112 surface-expression vector, and a recombinantL. lactisexpressing VP4 protein was constructed. An approximately 27 kDa VP4 protein was confirmed by SDS-PAGE , Western blot and immunostaining analysis. BALB/c mice were immunized orally with VP4-expression recombinantL. lactisand cellular, mucosal and systemic humoral immune responses were examined. Specific anti-VP4 secretory IgA and IgG were found in feces, ophthalmic and vaginal washes and in serum. The induced antibodies demonstrated neutralizing effects on porcine rotavirus infection on MA104 cells. Our findings suggest that oral immunization with VP4-expressingL. lactisinduced both specific local and systemic humoral and cellular immune responses in mice.

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