Serological and cellular non-responders in a long-term cross-sectional cohort of SARS-CoV-2-specific PCR-positive individuals

During the first pandemic wave, the dark figure of SARS-CoV-2 exposure was estimated to be high, however, an accelerated loss of antibodies was reported after about 6 months post infection. This study was performed to unveil the group of serological non-responders (NR) in PCR+ individuals 6-9 months after the first pandemic SARS-CoV-2 wave in spring 2020 and to evaluate their specific cellular immune response towards spike-molecule compared to PCR- and not PCR-tested (NT) household contact persons. SARS-CoV-2-specific antibodies were quantified using a commercial ELISA kit. The synergistic binding strength was assessed as relative avidity index (RAI) using ammonium-thiocyanate as chaotropic agent. The specific IFNγ-production in response to spike-protein was determined in spot-forming-units (SFU) by ELISPOT-assay. In PCR- 50.0%, in PCR+ 35.3% and in NT 20.7% had undetectable IgG-anti-SARS-CoV-2 and were considered non-responders (NR). All seropositive responders from the PCR-, 45.5% of PCR+ and 43.0% of NT developed high avidity (RAI>60%). In serological responders, cellular responses were detected in 75.0% PCR-, 75.8% PCR+ and 66.7% NT. In serological NR, positive SFU were found in 75.0% PCR-, 22.2% PCR+ and 17.4% NT. Significantly higher stimulation-indices were seen in PCR+ responders compared to PCR+ serological NR. Our findings showed that also PCR- and household contact persons who were not tested (NT) developed SARS-CoV-2-specific humoral and cellular immune responses. The relatively large proportion of serological non-responders but also the proportion of cellular non-responders within the group of IgG-positive individuals after PCR+ infection underlines the need for COVID-19 vaccinations in the reconvalescent group.

Download Full-text

Reduced Antibody and Cellular Immune Responses Following Dual COVID-19 Vaccination Within Infection-Naïve Residents of Long-Term Care Facilities

SSRN Electronic Journal ◽

10.2139/ssrn.3979590 ◽

2021 ◽

Author(s):

Gokhan Tut ◽

Tara Lancaster ◽

Megan S. Butler ◽

David Bone ◽

Nayandeep Kaur ◽

...

Keyword(s):

Immune Responses ◽

Long Term Care ◽

Term Care ◽

Cellular Immune Responses ◽

Care Facilities ◽

Cellular Immune

Download Full-text

Effect of immunization with Ii-key modified HER2 (776-790) peptide vaccine (AE37) on immunologic responses in prostate cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e16037 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e16037-e16037

Author(s):

Sonia A. Perez ◽

Eleftheria Anastasopoulou ◽

Efi Pappou ◽

Panagiotis Tzonis ◽

Stratos Bisias ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Patients ◽

Peptide Vaccine ◽

Treg Cells ◽

Vaccine Responses ◽

Cellular Immune Responses ◽

Cellular Immune ◽

Proliferation Assays

e16037 Background: We have shown that the AE37 vaccine (Ii-Key modified HER2(776-790) peptide) is safe and induces HER2/neu–specific cellular immune responses in patients with prostate cancer (Perez SA et al Clin. Cancer Res. 2010, 16:3495). We now present data from 4-year immunological assessments of prostate cancer patients who received AE37. Methods: Seventeen patients in a phase I study were given 6 doses of AE37 at monthly intervals and one additional dose a year after initiating treatment. Immunological testing to assess active versus suppressive immunity was conducted one month (intermediate-term immunomonitoring [ITI]) and 3 years (long-term immunomonitoring [LTI]) after the final dose of AE37. ELISPOT and proliferation assays were conducted to assess cytokine secretion and mitogenic response to antigen. DTH reactions were measured to assess in vivo immune response to antigen. All assays were conducted using native HER2(776-790) peptide (AE36). The percent Treg cells and ng/ml TGFβ were determined as markers for immune suppression. Results: Neither ELISPOT nor proliferation assays were statistically different at LTI compared to ITI. While clearly above pre-vaccine responses, the drop in DTH was statistically significant (p < 0.05). Similarly, the increase in Treg cells and circulating TGFβ was also statistically significant. An increase of >200 % in PSA-doubling time at any point during the study was observed in 6/17 patients, with 3 retaining this effect to 5 years. Conclusions: AE37 generates immunological memory associated with possible clinical efficacy in spite of Tregs and TGF-β levels returning at 4 years after being decreased for up to 6 months after initial AE37 vaccination. These results support further randomized testing of the AE37 vaccine. Clinical trial information: 2006-003299-37. [Table: see text]

Download Full-text

Reduced schedule of human anti rabies immunization with Fuenzalida & Palacios vaccine

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651989000100005 ◽

1989 ◽

Vol 31 (1) ◽

pp. 23-27 ◽

Cited By ~ 4

Author(s):

Carlos Roberto Zanetti ◽

Silvana Regina Favoretto ◽

Milene Silva Tino ◽

Avelino Albas ◽

Elizabeth Juliana G. Valentini ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Humoral Immune Response ◽

The Other ◽

Double Dose ◽

Humoral Immune ◽

Cellular Immune Responses ◽

Lymphoblastic Transformation ◽

Cellular Immune

The present study evaluates the humoral and cellular immune responses in 35 volunteers submited to short antirabies vaccination schedules with the Fuenzalida & Palacios vaccine based on the administration of doses on non consecutive days. The volunteers were divided into two groups. The first group received a total number of five doses given on days 0, 4, 7, 20 and 35. The other group received four doses, the first one being a double dose given on day 0 and than three other single doses on days 7, 20 and 35. The evaluation of humoral immune response was carried out by serum neutralization (SN) and indirect immunofluorescense (IIF) tests, while the cellular immune response was evaluated by lymphoblastic transformation assay (LTA) and skin test (ST). According to our results these reduced schedules elicited early and effective humoral and cellulafimmune responses to rabies antigen suggesting that new reduced schedules should be extensively studied in order to give the proper bases to the proposition of changes in the current long-term schedule.

Download Full-text

Cellular Immune Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent HPV Vaccine in Fijian Girls and Subsequent Responses to a Dose of Bivalent HPV Vaccine

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy147 ◽

2018 ◽

Vol 5 (7) ◽

Cited By ~ 3

Author(s):

Zheng Quan Toh ◽

Kathleen Wen Bei Cheow ◽

Fiona M Russell ◽

Edwin Hoe ◽

Rita Reyburn ◽

...

Keyword(s):

Cellular Immunity ◽

Hpv Vaccine ◽

Peripheral Blood Mononuclear ◽

Cellular Immune Responses ◽

Reduced Dose ◽

Specific Cellular Immune Response ◽

Hpv Types ◽

Cellular Immune ◽

The Impact ◽

High Disease Burden

Abstract Background This study examined the cellular immunity of 0, 1, 2, and 3 doses of Gardasil vaccine (4vHPV) in girls after 6 years and their responses to a subsequent dose of Cervarix vaccine (2vHPV). Methods A subset of girls (n = 59) who previously received 0, 1, 2, or 3 doses of 4vHPV 6 years earlier were randomly selected from a cohort study of Fijian girls (age 15–19 years). Blood was collected before and 28 days after a dose of 2vHPV. The HPV16- and HPV18-specific cellular immune response was determined by IFNγ-ELISPOT and by measurement of cytokines in peripheral blood mononuclear cell supernatants. Results Six years after 4vHPV vaccination, HPV18-specific responses were significantly lower in the 1- (1D) or 2-dose (2D) recipients compared with 3-dose recipients (2D: IFNγ-ELISPOT: P = .008; cytokines, IFNγ: P = .002; IL-2: P = .022; TNFα: P = .016; IL-10: P = .018; 1D: IL-2: P = .031; IL-10: P = .014). These differences were no longer significant post-2vHPV. No significant differences in HPV16 responses (except IL-2, P < .05) were observed between the 2- or 1-dose recipients and 3-dose recipients. Conclusions These data suggest that cellular immunity following reduced-dose schedules was detectable after 6 years, although the responses were variable between HPV types and dosage groups. The clinical significance of this is unknown. Further studies on the impact of reduced dose schedules are needed, particularly in high–disease burden settings.

Download Full-text

Extended interval BNT162b2 vaccination enhances peak antibody generation in older people

10.1101/2021.05.15.21257017 ◽

2021 ◽

Author(s):

Helen M Parry ◽

Rachel Bruton ◽

Christine Stephens ◽

Kevin Brown ◽

Gayatri Amirthalingam ◽

...

Keyword(s):

Immune Responses ◽

Older People ◽

Population Based ◽

Cellular Immune Responses ◽

Previous Infection ◽

Clinical Protection ◽

Cellular Immune ◽

Matched Samples

Abstract Objectives: To assess the relative immunogenicity of standard or extended interval BNT162b2 vaccination. Design: Population based cohort study comparing immune responses 2 weeks after the second vaccine, with appropriate time-matched samples in participants who received standard or extended interval double vaccination. Setting: Primary care networks, Birmingham, UK. December 2020 to April 2021. Participants: 175 people aged over 80 years of age. All donors received the BNT162b2 Pfizer/BioNTech vaccination and were vaccinated with either a standard 3 week interval between doses or an extended interval schedule. Main outcome measures: Peak quantitative spike-specific antibody and cellular immune responses. Results: In donors without evidence of previous infection the peak antibody response was 3.5-fold higher in donors who had undergone delayed interval vaccination. Cellular immune responses were 3.6-fold lower. Conclusion: Peak antibody responses after the second BNT162b2 vaccine are markedly enhanced in older people when this is delayed to 12 weeks although cellular responses are lower. Extended interval vaccination may therefore offer the potential to enhance and extend humoral immunity. Further follow up is now required to assess long term immunity and clinical protection.

Download Full-text

Adeno-Associated Viruses (AAV) and Host Immunity – A Race Between the Hare and the Hedgehog

Frontiers in Immunology ◽

10.3389/fimmu.2021.753467 ◽

2021 ◽

Vol 12 ◽

Author(s):

Kleopatra Rapti ◽

Dirk Grimm

Keyword(s):

Immune Responses ◽

Dorsal Root ◽

Transgene Expression ◽

State Of The Art ◽

Host Immunity ◽

Gene Therapies ◽

Cellular Immune Responses ◽

Cellular Immune

Adeno-associated viruses (AAV) have emerged as the lead vector in clinical trials and form the basis for several approved gene therapies for human diseases, mainly owing to their ability to sustain robust and long-term in vivo transgene expression, their amenability to genetic engineering of cargo and capsid, as well as their moderate toxicity and immunogenicity. Still, recent reports of fatalities in a clinical trial for a neuromuscular disease, although linked to an exceptionally high vector dose, have raised new caution about the safety of recombinant AAVs. Moreover, concerns linger about the presence of pre-existing anti-AAV antibodies in the human population, which precludes a significant percentage of patients from receiving, and benefitting from, AAV gene therapies. These concerns are exacerbated by observations of cellular immune responses and other adverse events, including detrimental off-target transgene expression in dorsal root ganglia. Here, we provide an update on our knowledge of the immunological and molecular race between AAV (the “hedgehog”) and its human host (the “hare”), together with a compendium of state-of-the-art technologies which provide an advantage to AAV and which, thus, promise safer and more broadly applicable AAV gene therapies in the future.

Download Full-text

Long Term Immune Response Produced by the SputnikV Vaccine

International Journal of Molecular Sciences ◽

10.3390/ijms222011211 ◽

2021 ◽

Vol 22 (20) ◽

pp. 11211

Author(s):

Ekaterina Martynova ◽

Shaimaa Hamza ◽

Ekaterina E. Garanina ◽

Emmanuel Kabwe ◽

Maria Markelova ◽

...

Keyword(s):

Immune Responses ◽

Research Centre ◽

High Potency ◽

S Protein ◽

Cellular Immune Responses ◽

Heptad Repeats ◽

Cellular Immune ◽

Multiple Domains ◽

Prolonged Response

SputnikV is a vaccine against SARS-CoV-2 developed by the Gamaleya National Research Centre for Epidemiology and Microbiology. The vaccine has been shown to induce both humoral and cellular immune responses, yet the mechanisms remain largely unknown. Forty SputnikV vaccinated individuals were included in this study which aimed to demonstrate the location of immunogenic domains of the SARS-CoV-2 S protein using an overlapping peptide library. Additionally, cytokines in the serum of vaccinated and convalescent COVID-19 patients were analyzed. We have found antibodies from both vaccinated and convalescent sera bind to immunogenic regions located in multiple domains of SARS-CoV-2 S protein, including Receptor Binding Domain (RBD), N-terminal Domain (NTD), Fusion Protein (FP) and Heptad Repeats (HRs). Interestingly, many peptides were recognized by immunized and convalescent serum antibodies and correspond to conserved regions in circulating variants of SARS-CoV-2. This breadth of reactivity was still evident 90 days after the first dose of the vaccine, showing that the vaccine has induced a prolonged response. As evidenced by the activation of T cells, cellular immunity strongly suggests the high potency of the SputnikV vaccine against SARS-CoV-2 infection.

Download Full-text