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.

A MATHEMATICAL MODEL TO ASSESS THE IMMUNE RESPONSE AGAINSTTRYPANOSOMA CRUZIINFECTION

2015 ◽  
Vol 23 (01) ◽  
pp. 131-163 ◽  
Author(s):  
HYUN MO YANG
Keyword(s):  
Mathematical Model ◽  
Trypanosoma Cruzi ◽  
Immune Responses ◽  
Cellular Response ◽  
Humoral Response ◽  
Cellular Responses ◽  
Cellular Immune Responses ◽  
Trivial Equilibrium ◽  
Cellular Immune ◽  
Cruzi Infection

A mathematical model is developed to assess humoral and cellular immune responses against Trypanosoma cruzi infection. Analysis of the model shows a unique non-trivial equilibrium, which is locally asymptotically stable, except in the case of a strong cellular response. When the proliferation of the activated CD8 T cells is increased, this equilibrium becomes unstable and a limit cycle appears. However, this behavior can be avoided by increasing the action of the humoral response. Therefore, unbalanced humoral and cellular responses can be responsible for long asymptomatic period, and the control of Trypanosoma cruzi infection is a consequence of well coordinated action of both humoral and cellular responses.

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 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 Dynamics of the Cellular and Humoral Immune Response After BNT162b2 Messenger Ribonucleic Acid Coronavirus Disease 2019 (COVID-19) Vaccination in COVID-19-Naive Nursing Home Residents

2021 ◽  
Author(s):  
Jens T Van Praet ◽  
Stefaan Vandecasteele ◽  
Anneleen De Roo ◽  
Matthijs Vynck ◽  
An S De Vriese ◽  
...  
Keyword(s):  
Nursing Home ◽  
Ribonucleic Acid ◽  
Cellular Response ◽  
Nursing Home Residents ◽  
Booster Vaccination ◽  
Humoral Response ◽  
Messenger Ribonucleic Acid ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Cellular Immune

Abstract Short-term humoral and cellular immune responses are diminished after BNT162b2 messenger ribonucleic acid coronavirus disease 2019 (COVID-19) vaccination in COVID-19-naive nursing home residents, a population particularly vulnerable to the disease. We found both responses to decline after 4 weeks and remain lower than those of healthcare workers after 24 weeks, with an estimated half-life of the antibody response of 47 days. At 4 weeks, older age was significantly associated with a decreased humoral response, and diabetes mellitus and active malignancy were associated with a decreased cellular response. Our results imply that COVID-19-naive nursing home residents are a target group for booster vaccination trials.

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 Selected prfA* Mutations in Recombinant Attenuated Listeria monocytogenes Strains Augment Expression of Foreign Immunogens and Enhance Vaccine-Elicited Humoral and Cellular Immune Responses

2008 ◽  
Vol 76 (8) ◽  
pp. 3439-3450 ◽  
Author(s):  
Lin Yan ◽  
Jin Qiu ◽  
Jianbo Chen ◽  
Bridgett Ryan-Payseur ◽  
Dan Huang ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Immune Responses ◽  
Wild Type ◽  
Vaccine Vectors ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Anticancer Vaccines ◽  
Constitutive Overexpression ◽  
Cellular Immune

ABSTRACT While recombinant Listeria monocytogenes strains can be explored as vaccine candidates, it is important to develop attenuated but highly immunogenic L. monocytogenes vaccine vectors. Here, prfA* mutations selected on the basis of upregulated expression of L. monocytogenes PrfA-dependent genes and proteins were assessed to determine their abilities to augment expression of foreign immunogens in recombinant L. monocytogenes vectors and therefore enhance vaccine-elicited immune responses (a prfA* mutation is a mutation that results in constitutive overexpression of PrfA and PrfA-dependent virulence genes; the asterisk distinguishes the mutation from inactivation or stop mutations). A total of 63 recombinant L. monocytogenes vaccine vectors expressing seven individual viral or bacterial immunogens each in nine different L. monocytogenes strains carrying wild-type prfA or having prfA* mutations were constructed and investigated. Mutations selected on the basis of increased PrfA activation in recombinant L. monocytogenes prfA* vaccine vectors augmented expression of seven individual protein immunogens remarkably. Consistently, prime and boost vaccination studies with mice indicated that the prfA(G155S) mutation in recombinant L. monocytogenes ΔactA prfA* strains enhanced vaccine-elicited cellular immune responses. Surprisingly, the prfA(G155S) mutation was found to enhance vaccine-elicited humoral immune responses as well. The highly immunogenic recombinant L. monocytogenes ΔactA prfA* vaccine strains were as attenuated as the recombinant parent L. monocytogenes ΔactA vaccine vector. Thus, recombinant attenuated L. monocytogenes ΔactA prfA* vaccine vectors potentially are better antimicrobial and anticancer vaccines.

Idiotype Vaccination of Untreated Indolent B-Cell Lymphoma: Durable Objective Remissions and Association of Superior Outcome with Cellular Immune Responses

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 235-235 ◽  
Author(s):  
Marcelo A. Navarrete ◽  
Kristina Heining-Mikesch ◽  
Cristina Bertinetti-Lapatki ◽  
Marcus Duehren-von Minden ◽  
Andrea Hafkemeyer ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Immune Responses ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Humoral Immune ◽  
Cellular Immune Responses ◽  
Humoral Immune Responses ◽  
Cellular Immune

Abstract Idiotype vaccination refers to active immunization of B-cell lymphoma (B-NHL) patients with the clonal immunoglobulin (Ig) expressed by the tumor cells. After systemic cytoreductive therapy, idiotype vaccination has been shown to induce specific cellular and humoral immune responses; and humoral responses in particular are associated with prolonged remission and encouraging survival rates. Conventional idiotype vaccines are composed of the entire lymphoma-derived Ig coupled to the immunogenic carrier KLH and are administered subcutaneously with adjuvant. We have developed a idiotype production strategy based on bacterial expression of the lymphoma-derived idiotype as a recombinant Fab fragment (Bertinetti et al., EJH 2006). Intradermal administration of this antigen with lipid-based adjuvant and subcutaneous coadministration of GM-CSF had excellent immunogenicity in a phase I trial of advanced, heavily pretreated B-NHL patients (Bertinetti et al., Cancer Research 2006). In a subsequent phase II trial, 20 patients with untreated indolent B-NHL (14 follicular [FL], 3 nodal marginal zone [nMZL], 3 mantle cell [MCL]) and without immediate need for cytoreduction received at least 6 monthly idiotype vaccinations. No grade IV toxicities were seen, and the sole case of grade III toxicity, generalized erythema, did not preclude completion of the vaccination schedule. Prior to vaccination, 5/19 patients (26%) had decreased CD4+ and 6/19 patients (31%) low CD8+ T cells counts. Furthermore, 10/12 anti-HbS-negative patients (83%) failed to mount a detectable immune response to a conventional hepatitis B vaccine administered concomitantly to idiotype vaccination. Despite this functional immunodeficiency, 12/18 analyzed patients (66%) developed a cellular immune response to idiotype as detected by enumeration of IFNgamma-secreting cells by DC-ELISpot. The ELISpot protocol was validated by blinded interlaboratory testing (www.cimt.de). The frequency of idiotype-responding T cells increased from the 2nd to the 6th vaccination and could be effectively boostered by maintenance immunization in 3-monthly intervals. In vitro stimulation of PBMC from responding patients with idiotype induced specific proliferation of CD4+ T-cells and a shift towards a Th1 response in post-vaccination samples. In addition, 8/18 analyzed patients (44%) developed anti-idiotype IgG or IgM antibodies as assessed by ELISA, and the combined immune response rate was 85%. After a median follow-up of 34 months, 8 patients (40%) are progression-free, and 10 (50%) did not require cytoreductive therapy. Cellular immune responses were associated with superior PFS (p<0.05), and 5 of 6 non-responders eventually required cytoreductive therapy. Humoral immune responses were not related to PFS. Six patients (30%; only FL or nMZL) achieved an objective partial remission, including near-complete disappearance of a large submandibular mass and one subcutaneous lymphoma mass. All objective responders developed specific cellular immunity, but only 4 anti-idiotype antibodies. Five patients are in continuing remission for 12–49 months. Intradermal immunization with the chosen idiotype formulation has excellent immunogenicity despite a severely impaired immune function in untreated B-NHL patients. Furthermore, this is the first active immunotherapy trial showing objective and durable lymphoma responses in first-line therapy at a higher rate than expected for spontaneous remissions. In this setting, and in contrast to conventional idiotype vaccination schedules, cellular anti-idiotype immunity may play a crucial role for a favorable clinical outcome. Since passive humoral anti-lymphoma immunity can be easily transferred by infusions of commercially available monoclonal antibodies, synergistic benefit may be envisioned for an initial vaccination course aimed to prime anti-idiotype T-cells combined with subsequent passive immunotherapy.

Variation in class-specific humoral immune responses of different mouse strains to microfilariae ofDipetalonema viteae

Parasitology ◽  
1987 ◽  
Vol 95 (3) ◽  
pp. 559-568 ◽  
Author(s):  
N. M. Almond ◽  
M. J. Worms ◽  
W. Harnett ◽  
R. M. E. Parkhouse
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Significant Variation ◽  
Humoral Response ◽  
Antibody Responses ◽  
Mouse Strains ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Subcutaneous Transplantation ◽  
Dipetalonema Viteae

SUMMARYThe class-specific antibody responses of 3 strains of mice (C57/Bl10, BALB/C and CBA/N) known to vary in their ability to control the microfilaraemia which follows the subcutaneous transplantation of adult femaleDipetalonema viteaehas been investigated. The 3 mouse strains showed significant variation (a) in total levels of immunoglobulins and (b) in ability to recognize individual radio-isotope-labelled antigens as measured by coprecipitation. Within each mouse strain it was noted that antigens could vary with respect to the nature of the isotype of the antibody response which they elicited. Furthermore, by comparing results obtained from class-specific coprecipitation with surface ELISA it was found that a similar variation between responses to individual epitopes was also likely. No differences were observed in the humoral response of the 3 mouse strains which could explain the known resistance of the C57/B110 strain; reasons for this are discussed.

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.

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