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1.
Front Immunol ; 13: 1027180, 2022.
Article in English | MEDLINE | ID: covidwho-2109770

ABSTRACT

Under the background of the severe human health and world economic burden caused by COVID-19, the attenuation of vaccine protection efficacy, and the prevalence and immune escape of emerging variants of concern (VOCs), the third dose of booster immunization has been put on the agenda. Systems biology approaches can help us gain new perspectives on the characterization of immune responses and the identification of factors underlying vaccine-induced immune efficacy. We analyzed the antibody signature and transcriptional responses of participants vaccinated with COVID-19 inactivated vaccine and protein subunit vaccine as a third booster dose. The results from the antibody indicated that the third booster dose was effective, and that heterologous vaccination with the protein subunit vaccine as a booster dose induced stronger humoral immune responses than the homologous vaccination with inactivated vaccine, and might be more effective against VOCs. In transcriptomic analysis, protein subunit vaccine induced more differentially expressed genes that were significantly associated with many important innate immune pathways. Both the homologous and heterologous boosters could increase the effectiveness against COVID-19, and compared with the inactivated vaccine, the protein subunit vaccine, mediated a stronger humoral immune response and had a more significant correlation with the innate immune function module, which provided certain data support for the third booster immunization strategy.


Subject(s)
COVID-19 , Immunity, Humoral , Humans , Transcriptome , Protein Subunits , Immunization, Secondary , COVID-19/prevention & control , Vaccines, Inactivated , Vaccines, Subunit
3.
Bull Exp Biol Med ; 173(6): 734-739, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2094660

ABSTRACT

IgM and IgG antibodies to the SARS-CoV-2 virus are detected in subjects who have recovered from COVID-19; IgM antibodies persist in a 1/3 of infected subjects up to 12 months from the moment of the disease, while IgG antibodies are present in the vast majority of cases (97%; medium and high levels antibodies were registered in 85% of cases). By the 12th month, 40% of those who recovered still have a very high level of IgG antibodies to the S-protein (>500 BAU/ml). In the feces, urine, and blood serum of patients with long-term persistent IgM antibodies, no coronavirus antigens were detected. After vaccination with the Gam-COVID-Vac vaccine, IgG antibodies to the S-protein are detected in 100% of cases and remain at a high level for 4 months, by the 5-6th month, the level of antibodies decreases. During revaccination, the level of IgG antibodies to S-protein reaches high values earlier than during primary vaccination, and remains high for 4 months (observation period). The blood sera of recovered and vaccinated patients have a high virus-neutralizing activity (at least 1:80), while its level is somewhat higher in recovered patients.


Subject(s)
Antibodies, Viral , COVID-19 , Humans , Immunization, Secondary , COVID-19/prevention & control , SARS-CoV-2 , Vaccination , Immunoglobulin M , Immunoglobulin G
4.
J Med Virol ; : e28258, 2022 Oct 27.
Article in English | MEDLINE | ID: covidwho-2085072

ABSTRACT

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.

5.
Vaccine ; 40(48): 6971-6978, 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2082750

ABSTRACT

BACKGROUND AND AIMS: Recent studies have reported poor humoral immune response to mRNA vaccines in patients with chronic liver disease (CLD). However, the immunogenicity of ChAdOx1 (vector-based) and BBV152 (inactivated virus) vaccines in patients with CLD and liver transplant recipients (LTRs) is unknown. Therefore, we aimed to assess the immunogenicity of ChAdOx1 and BBV152 vaccines in patients with CLD (including cirrhosis patients) and LTRs. METHODS: In this single-center prospective study, consecutive completely vaccinated (ChAdOx1 or BBV152) non-cirrhosis CLD patients, those with cirrhosis, and LTRs were compared with matched healthy controls for anti-spike antibody and cellular response. RESULTS: Sixty healthy individuals, 50 NCCLD patients, 63 compensated and 50 decompensated cirrhosis, and 17 LTRs were included. The proportion of non-responders was similar among the healthy control (8 %), non-cirrhosis CLD (16 %), and compensated cirrhosis groups (17.5 %;p = 0.3). However, a higher proportion of patients with decompensated cirrhosis (34 %) and LTRs (59 %) were non-responders than the healthy controls (p = 0.001). Cluster of differentiation (CD) 4-effector cells were lower in patients with non-cirrhosis CLD and compensated cirrhosis. CD4-naïve, CD4-effector, B, and B-memory cells were lower in the decompensated cirrhosis group. Although the central memory cells were higher in the decompensated cirrhosis group, they could not differentiate into effector cells. CD4- and CD8-naïve cells were higher in the marrow in the LTRs, while the CD4-effector memory cells and CD4- and CD8-effector cells were lower in the LTRs. Furthermore, B cells were more deficient in the LTRs, suggesting poor antibody response. CONCLUSION: Patients with decompensated cirrhosis and LTRs demonstrated suboptimal humoral and cellular immune responses against recombinant and inactivated COVID-19 vaccines.


Subject(s)
COVID-19 , Coronavirus , Liver Diseases , Liver Transplantation , Humans , COVID-19 Vaccines , Prospective Studies , Liver Cirrhosis , Immunity , Transplant Recipients
6.
Embase; 28.
Preprint in English | EMBASE | ID: ppcovidwho-346602

ABSTRACT

Chronic infection with human cytomegalovirus (CMV) may contribute to poor vaccine efficacy in older adults. We assessed effects of CMV serostatus on antibody quantity and quality, as well as cellular memory recall responses, after 2 and 3 SARS-CoV-2 mRNA vaccine doses, in older adults in assisted living facilities. CMV serostatus did not affect anti-Spike and anti-RBD IgG antibody levels, nor neutralization capacity against wildtype or beta variants of SARS-CoV-2 several months after vaccination. CMV seropositivity altered T cell expression of senescence-associated markers and increased TEMRA cell numbers, as has been previously reported;however, this did not impact Spike-specific CD4+ T cell memory recall responses. CMV seropositive individuals did not have a higher incidence of COVID-19, though prior infection influenced humoral immunity. Therefore, CMV seropositivity may alter T cell composition but does not impede the durability of humoral protection or cellular memory responses after SARS-CoV-2 mRNA vaccination in older adults. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.

7.
J Med Virol ; 2022 Oct 18.
Article in English | MEDLINE | ID: covidwho-2075083

ABSTRACT

With the continuation of the coronavirus disease 2019 pandemic and the emergence of new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants, the control of the spread of the virus remains urgent. Various animals, including cats, ferrets, hamsters, nonhuman primates, minks, tree shrews, fruit bats, and rabbits, are susceptible to SARS-CoV-2 infection naturally or experimentally. Therefore, to avoid animals from becoming mixing vessels of the virus, vaccination of animals should be considered. In the present study, we report the establishment of an efficient and stable system using Newcastle disease virus (NDV) as a vector to express SARS-CoV-2 spike protein/subunit for the rapid generation of vaccines against SARS-CoV-2 in animals. Our data showed that the S and S1 protein was sufficiently expressed in rNDV-S and rNDV-S1-infected cells, respectively. The S protein was incorporated into and displayed on the surface of rNDV-S viral particles. Intramuscular immunization with rNDV-S was found to induce the highest level of binding and neutralizing antibodies, as well as strong S-specific T-cell response in mice. Intranasal immunization with rNDV-S1 provoked a robust T-cell response but barely any detectable antibodies. Overall, the NDV-vectored vaccine candidates were able to induce profound humoral and cellular immunity, which will provide a good system for developing vaccines targeting both T-cell and antibody responses.

8.
Eur J Immunol ; 2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2074970

ABSTRACT

Memory T cell responses have been analyzed only in small cohorts of COVID-19 vaccines. Herein, we aimed to assess anti-SARS-CoV-2 cellular immunity in a large cohort using QuantiFERON assays, which are IFN-γ release assays (IGRAs) based on short-term whole blood culture. The study included 571 individuals receiving the viral spike (S) protein-expressing BNT162b2 mRNA vaccine. QuantiFERON assays revealed antigen-specific IFN-γ production in most individuals 8 weeks after the second dose. Simultaneous flow cytometric assays to detect T cells expressing activation-induced markers (AIMs) performed for 28 randomly selected individuals provided data correlating with the QuantiFERON data. Simultaneous IFN-γ enzyme-linked immunospot and AIM assays for another subset of 31 individuals, based on short-term peripheral blood mononuclear cell culture, also indicated a correlation between IFN-γ production and AIM positivity. These observations indicated the acquisition of T cell memory responses and supported the usability of IGRAs to assess cellular immunity. The QuantiFERON results were weakly correlated with serum IgG titers against the receptor-binding domain of the S protein and were associated with pre-vaccination infection and adverse reactions after the second dose. The present study revealed cellular immunity after COVID-19 vaccination, providing insights into the effects and adverse reactions of vaccination.

9.
Vaccines (Basel) ; 10(10)2022 Oct 11.
Article in English | MEDLINE | ID: covidwho-2071924

ABSTRACT

Kidney transplant recipients (KTRs) are at a much higher risk of complications and death following COVID-19 and are poor vaccine responders. The data are limited on the immune response to Covishield® in KTRs. We prospectively recruited a cohort of 67 KTRs aged >18 between April 2021 and December 2021. Each participant was given two intramuscular doses of Covishield®, each of 0.5 mL, at an interval of 12 weeks. A blood specimen of 5.0 mL was collected from each participant at two points within a few days before administering the first dose of the vaccine and at any time between 4-12 weeks after administering the second dose. The sera were tested for anti-RBD antibody (ARAb) titre and neutralising antibody (NAb). An ACE2 competition assay was used as a proxy for virus neutralization. According to the prior COVID-19 infection, participants were grouped as (i) group A: prior symptomatic COVID-19 infection, (ii) group B: prior asymptomatic COVID-19 infection as evidenced by detectable ARAb in the prevaccination specimen, (iii) Group C: no prior infection with COVID-19, (iv) group D: Unclassified, i.e., participants had no symptoms suggestive of COVID-19, but their prevaccination specimen was not available for ARAb testing before vaccination. Fifty of sixty-seven participants (74.6%) provided paired specimens (group A 14, group B 27, and group C 9) and 17 participants (25.4%) provided only postvaccination specimens (group D). In the overall cohort (n = 67), 91% and 77.6% of participants developed ARAb and NAb, respectively. Their ARAb titre and NAb proportion were 2927 (520-7124) U/mL and 87.9 (24.4-93.2) %, respectively. Their median ARAb titre increased 65.6 folds, from 38.2 U/mL to 3137 U/mL. Similarly, the proportion of participants with NAb increased from 56% to 86%, and the NAb proportion raised 2.7 folds, from 23% to 91%. A comparison of vaccine response between the study groups showed that all those with or without prior COVID-19 infection showed a significant rise in ARAb titre (p < 0.05) and NAb proportion (p < 0.05) after the two doses of vaccine administration. The median value of folds rise in anti-RBD and NAb between groups A and B were comparable. Hence, ARAb is present in more than 3/4th of KTRs before the ChAdOx1 vaccine in India. The titer of ARAb and the proportion of NAb significantly increased after the two doses of the ChAdOx1 vaccine in KTRs.

10.
Emerg Microbes Infect ; 11(1): 2359-2370, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2070053

ABSTRACT

Viral vectors are a potent vaccine platform for inducing humoral and T-cell immune responses. Among the various viral vectors, replication-competent ones are less commonly used for coronavirus disease 2019 (COVID-19) vaccine development compared with replication-deficient ones. Here, we show the availability of a smallpox vaccine LC16m8Δ (m8Δ) as a replication-competent viral vector for a COVID-19 vaccine. M8Δ is a genetically stable variant of the licensed and highly effective Japanese smallpox vaccine LC16m8. Here, we generated two m8Δ recombinants: one harbouring a gene cassette encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein, named m8Δ-SARS2(P7.5-S)-HA; and one encoding the S protein with a highly polybasic motif at the S1/S2 cleavage site, named m8Δ-SARS2(P7.5-SHN)-HA. M8Δ-SARS2(P7.5-S)-HA induced S-specific antibodies in mice that persisted for at least six weeks after a homologous boost immunization. All eight analysed serum samples displayed neutralizing activity against an S-pseudotyped virus at a level similar to that of serum samples from patients with COVID-19, and more than half (5/8) also had neutralizing activity against the Delta/B.1.617.2 variant of concern. Importantly, most serum samples also neutralized the infectious SARS-CoV-2 Wuhan and Delta/B.1.617.2 strains. In contrast, immunization with m8Δ-SARS2(P7.5-SHN)-HA elicited significantly lower antibody titres, and the induced antibodies had less neutralizing activity. Regarding T-cell immunity, both m8Δ recombinants elicited S-specific multifunctional CD8+ and CD4+ T-cell responses even after just a primary immunization. Thus, m8Δ provides an alternative method for developing a novel COVID-19 vaccine.


Subject(s)
COVID-19 , Smallpox Vaccine , Viral Vaccines , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Mice , SARS-CoV-2/genetics , Smallpox Vaccine/genetics , Spike Glycoprotein, Coronavirus/genetics
11.
Pediatricheskaya Farmakologiya ; 19(2):196-200, 2022.
Article in Russian | EMBASE | ID: covidwho-2067387

ABSTRACT

Background. Students, as the most active and mobile part of population, often unite into educational and informal groups, move to other regions or countries, and present a specific risk group for the spread of new coronavirus infection. Thus, they require preventive vaccination. objective. the aim of the study is to study the immunological potency, tolerance, and efficacy of GamCOVID-Vac vaccine among students of Krasnodar. methods. 119 seronegative students (18–30 years old) were examined. SARSCoV-2 IgG (ELISA method) was determined 1, 3, and 6 months after two completed rounds of vaccination. Post-vaccination adverse events and COVID-19 cases were evaluated in the study. results. SARS-CoV-2 IgG level 1 month after vaccination ranged from 6.15 to 19.38 and was to 16.39 (AU/mL) ± 1,12. Immunological potency values ranged from 4.407 to 21.5 (AU/mL) (14.74 ± 2.93) 3 months after. IgG titers were in the range of 4.14 to 17.71 (AU/mL) (10.97 ± 4.69) 6 months after. Adverse events after vaccination were revealed in 34 respondents (28.6%). Among them, local (hyperemia, pain, edema) — 21 (17.6%): slight — 90.4%, major — 9.6%;general (fever, weakness, algor, headache, arthralgia, myalgia) — 13 (10.9%): slight — 69.2%, major — 30.8%. The increase in vaccination coverage in students from 30.3 to 79.1% reduced the COVID-19 morbidity from 3.81 to 1.57%. conclusion. Gam-COVID-Vac vaccine induced stable humoral response, demonstrated sufficient safety, and reduced morbidity 2.4-fold.

12.
Journal of Clinical and Diagnostic Research ; 16(9):DC12-DC17, 2022.
Article in English | EMBASE | ID: covidwho-2067199

ABSTRACT

Introduction: Bharat Biotech International Ltd in partnership with National Institute of Virology (NIV), has developed an indigenous whole virion inactivated Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) viral vaccine BBV-152 (Covaxin), formulated with Toll Like Receptors 7/8 agonist Imidazoquinoline (IMDG) molecule adsorbed to alum (Algel). Variety of factors other than environmental ones can affect vaccines efficiency outside the strict setting of clinical trials, like how the vaccine is stored or transported, and even how patients are vaccinated. In addition, the intrinsic capacity of the recipient to respond to a vaccine which is determined by sex, genetic factors, age, psychological stress, nutrition and other diseases are also likely to have an impact. Aim(s): To determine the safety, reactogenicity and immunogenicity of the inactivated whole virus vaccine (Covaxin) amongst hospital-based population groups. Material(s) and Method(s): The prospective analytical study was conducted in the Department of Microbiology, Sawai Man Singh Medical College, Jaipur, Rajasthan, India, from January 2021 to March 2021.The study primarily included Healthcare Workers (HCWs) employed at SMS Medical college and attached hospitals. In-vitro quantitative IgG antibodies against SARS-CoV-2 spike Receptor Binding Domain (RBD) were measured using Chemiluminescence Immunoassay (CLIA) based Advia centaur SARS-CoV-2 IgG, manufactured by Siemens Pvt Ltd, Munich, Germany, as per manufacture's instructions. Result(s): Out of total 223 individuals, 61.88 % (138/223) showed neutralising antibody titre of >1 index value by CLIA, rest 38.12% (85/223) were non reactive i.e., titre <1 index value, after four weeks of receiving first dose of Covaxin. After 2 to 4 weeks of receiving second dose 84.30% (188/223) showed neutralising antibody titre of >1 index value by CLIA, rest 15.70% (35/223) were non reactive i.e., titre <1 index value. After receiving first dose, 100% (223/223) of the participants developed localised pain and bodyache 33.63% (75/223). None of the participants showed any anaphylactic reaction or any emergency condition just after vaccination. Conclusion(s): Covaxin is a well-tolerated vaccine, and induces good humoral response against SARS-CoV-2 with a significant rise in the neutralising antibody titres. Copyright © 2022 Journal of Clinical and Diagnostic Research. All rights reserved.

13.
J Clin Med ; 11(19)2022 Oct 10.
Article in English | MEDLINE | ID: covidwho-2066211

ABSTRACT

Age has been found to be the single most significant factor in COVID-19 severity and outcome. However, the age-related severity factors of COVID-19 have not been definitively established. In this study, we detected SARS-CoV-2-specific antibody responses and infectious disease-related blood indicators in 2360 sera from 783 COVID-19 patients, with an age range of 1-92 years. In addition, we recorded the individual information and clinical symptoms of the patients. We found that the IgG responses for S1, N, and ORF3a and the IgM for NSP7 were associated with severe COVID-19 at different ages. The IgM responses for the S-protein peptides S1-113 (aa 673-684) and S2-97 (aa 1262-1273) were associated with severe COVID-19 in patients aged <60. Furthermore, we found that the IgM for S1-113 and NSP7 may play a protective role in patients aged <60 and >80, respectively. Regarding clinical parameters, we analyzed the diagnostic ability of five clinical parameters for severe COVID-19 in six age groups and identified three-target panel, glucose, IL-6, myoglobin, IL-6, and NT proBNP as the appropriate diagnostic markers for severe COVID-19 in patients aged <41, 41-50, 51-60, 61-70, 71-80, and >80, respectively. The age-associated severity factors revealed here will facilitate our understanding of COVID-19 immunity and diagnosis, and eventually provide meaningful information for combating the pandemic.

14.
Microbiol Spectr ; : e0271622, 2022 Oct 11.
Article in English | MEDLINE | ID: covidwho-2063987

ABSTRACT

Secretory immunoglobulin A (IgA) plays a crucial role in mucosal immunity for preventing the invasion of exogenous antigens; however, little is understood about the neutralizing activity of serum IgA. Here, to examine the role of IgA antibodies against COVID-19 illnesses, we determined the neutralizing activity of serum/plasma IgG and IgA purified from previously SARS-CoV-2-infected and COVID-19 mRNA vaccine-receiving individuals. We found that serum/plasma IgA possesses substantial but rather modest neutralizing activity against SARS-CoV-2 compared to IgG with no significant correlation with the disease severity. Neutralizing IgA and IgG antibodies achieved the greatest activity at approximately 25 and 35 days after symptom onset, respectively. However, neutralizing IgA activity quickly diminished to below the detection limit approximately 70 days after onset, while substantial IgG activity was observed until 200 days after onset. The total neutralizing activity in sera/plasmas of those with COVID-19 largely correlated with those in purified IgG and purified IgA and levels of anti-SARS-CoV-2-S1-binding IgG and anti-SARS-CoV-2-S1-binding IgA. In individuals who were previously infected with SARS-CoV-2 but had no detectable neutralizing IgA activity, a single dose of BNT162b2 or mRNA-1273 elicited potent serum/plasma-neutralizing IgA activity, but the second dose did not further strengthen the neutralization antibody response. The present data show that the systemic immune stimulation with natural infection and COVID-19 mRNA-vaccines elicits both SARS-CoV-2-specific neutralizing IgG and IgA responses in serum, but the IgA response is modest and diminishes faster than the IgG response. IMPORTANCE Secretory dimeric immunoglobulin A (IgA) plays an important role in preventing the invasion of foreign objects by its neutralizing activity on mucosal surfaces, while monomeric serum IgA is thought to relate to the phagocytic immune system activation. Here, we report that individuals with the novel coronavirus disease (COVID-19) developed both systemic neutralizing IgG (nIgG) and IgA (nIgA) active against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the nIgA response was quick and reached the highest activity earlier than the nIgG response, nIgA activity was modest and diminished faster than nIgG activity. In individuals who recovered from COVID-19 but had no detectable nIgA activity, a single dose of COVID-19 mRNA vaccine elicited potent nIgA activity, but the second dose did not further strengthen the antibody response. Our study provides novel insights into the role and the kinetics of serum nIgA against the pathogen in both naturally infected and COVID-19 mRNA vaccine-receiving COVID-19-convalescent individuals.

15.
RMD Open ; 8(2) (no pagination), 2022.
Article in English | EMBASE | ID: covidwho-2064276

ABSTRACT

Objectives Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are overlapping autoinflammatory diseases affecting people over 50 years. The diseases are treated with immunosuppressive drugs such as prednisolone, methotrexate, leflunomide and tocilizumab. In this study, we assessed the immunogenicity and safety of SARS-CoV-2 vaccinations in these diseases (based on humoral and cellular immunity). Methods Patients (n=45 GCA, n=33 PMR) visited the outpatient clinic twice: pre-vaccination and 4 weeks after the second dose (BNT162b2 or ChAdOx1 vaccine). Patients with previous SARS-CoV-2 infection were excluded. In both pre-vaccination and post-vaccination samples, anti-Spike antibody concentrations were assessed and compared with age-, sex-and vaccine-matched control groups (n=98). In addition, the frequency of SARS-CoV-2 Spike-specific T-cells was assessed by IFN-gammaELIspot assay, and side effects and disease activity were recorded. Results GCA/PMR patients did not have reduced antibody concentrations compared with controls. However, linear regression analysis revealed a significant association of methotrexate and >10 mg/day prednisolone use with lower antibody concentrations in GCA/PMR patients. Evidence of cellular immunity, as assessed by ELIspot assay, was found in 67% of GCA/PMR patients. Patients using >10 mg/day prednisolone had reduced cellular immunity. Importantly, vaccination did not lead to significant side effects or changes in disease activity. Conclusions SARS-CoV-2 vaccination was safe for GCA/PMR patients and immunogenicity was comparable to other older individuals. However, patients using methotrexate and particularly >10 mg/day prednisolone did show lower vaccine responses, which corroborates findings in other autoinflammatory patient populations. These patients may therefore be at higher risk of (potentially even severe) breakthrough SARS-CoV-2 infection. Copyright ©

16.
BMJ Open ; 12(9), 2022.
Article in English | EMBASE | ID: covidwho-2064156

ABSTRACT

Purpose To investigate the robustness and longevity of SARS-CoV-2 immune responses conferred by natural infection and vaccination among priority populations such as immunocompromised individuals and people with post-acute sequelae of COVID-19 in a prospective cohort study (Stop the Spread Ottawa - SSO) in adults living in the Ottawa region. In this paper, we describe the study design, ongoing data collection and baseline characteristics of participants. Participants Since October 2020, participants who tested positive for COVID-19 (convalescents) or at high risk of exposure to the virus (under surveillance) have provided monthly blood and saliva samples over a 10-month period. As of 2 November 2021, 1026 adults had completed the baseline survey and 976 had attended baseline bloodwork. 300 participants will continue to provide bimonthly blood samples for 24 additional months (ie, total follow-up of 34 months). Findings to date The median age of the baseline sample was 44 (IQR 23, range: 18-79) and just over two-thirds (n=688;67.1%) were female. 255 participants (24.9%) had a history of COVID-19 infection confirmed by PCR and/or serology. Over 600 participants (60.0%) work in high-risk occupations (eg, healthcare, teaching and transportation). 108 participants (10.5%) reported immunocompromising conditions or treatments at baseline (eg, cancer, HIV, other immune deficiency, and/or use of immunosuppressants). Future plans SSO continues to yield rich research potential, given the collection of pre-vaccine baseline data and samples from the majority of participants, recruitment of diverse subgroups of interest, and a high level of participant retention and compliance with monthly sampling. The 24-month study extension will maximise opportunities to track SARS-CoV-2 immunity and vaccine efficacy, detect and characterise emerging variants, and compare subgroup humoral and cellular response robustness and persistence.

17.
American Journal of Transplantation ; 22(Supplement 3):638-639, 2022.
Article in English | EMBASE | ID: covidwho-2063546

ABSTRACT

Purpose: Solid organ transplant recipients (SOTR) develop weak antibody responses after SARS-CoV-2 vaccination. Published data on neutralizing activity of plasma, a better measure of protection, in SOTR following an additional dose of SARSCoV- 2 vaccine is limited. Method(s): Plasma was longitudinally collected from SOTR following initial COVID- 19 vaccination. Neutralizing activity against SARS-CoV-2 was assessed using the cPass Neutralization Antibody Detection Kit (GenScript, Biotech). ELISAs were performed against SARS-CoV-2 proteins (S1, N, RBD), CMV (glycoprotein B), Influenza A H1N1 (nucleoprotein), HSV-1, EBV glycoprotein (gp350), and tetanus toxoid for comparison. Result(s): Demographic and clinical characteristics are summarized in table 1. No participants had evidence of COVID-19 infection as IgG titers to SARS-CoV-2 N protein were low. Neutralizing activity against SARS-CoV-2 RBD was observed in 39.6% of individuals (N=21/53) ~93 days after initial vaccination. Participants with neutralizing activity were more likely to have received a liver transplant (47.6% vs 6.25%, p=0.001), and less likely to be on an anti-metabolite (52.4% vs. 87.5%, p=0.009) or triple immunosuppression (14.3% vs. 53.1%, p=0.008). After an additional vaccine dose, 78.1% (N=25/32) of participants developed neutralizing activity with significant increases in viral neutralization (figure 1, median 36.8% [95%CI 18.9-64.6] to 97.2% [95%CI 74.0-98.9], p<0.0001). Participants with low neutralizing activity demonstrated adequate antibody titers to other microbial antigens (figure 2). Conclusion(s): An additional dose of SARS-CoV-2 vaccine increased the number of SOTR with neutralizing activity and the magnitude of the seroresponse. SOTR with low neutralizing activity maintain humoral responses to other microbial antigens suggesting the diminished seroresponse might be related to inhibition of new B cell responses.

18.
American Journal of Transplantation ; 22(Supplement 3):1016, 2022.
Article in English | EMBASE | ID: covidwho-2063533

ABSTRACT

Purpose: Torque tenovirus (TTV), a highly prevalent virus which is not known to cause pathology in humans, is currently being investigated as a marker of immunosuppression. In this study we investigated if the TTV load measured prior to COVID-19 vaccination can predict the serological response to the COVID-19 vaccine, measured 28 days after the second vaccination dose. Method(s): The humoral response to the mRNA 1273 vaccine (Moderna) was assessed in Lung transplant recipients (LTR) who received a transplant between 4 and 237 months prior, by measuring Spike-specific IgG levels at 28 days after the second vaccination. Antibody concentrations of >10 BAU/ml were considered reactive. TTV loads were determined by PCR and Pearson's correlation coefficient was calculated to correlate serological responses to TTV load. Patient characteristics, including reasons for transplantation, antirejection treatment, age and time since transplantation, were recorded to assess associations between these factors and vaccination response or TTV levels. Result(s): 103 LTR were included of which 41 (40%) showed some response (>10 BAU/ml) to the vaccine at 28 days after the second vaccination. 61 (60%) were non-responders. TTV loads at baseline varied between negative and 10E9 copies/ ml. The TTV loads were found to correlate with IgG levels and the with the percentage of responders 28 days after the second vaccination (=<0.001). TTV loads also correlated strongly with the time since transplantation. High TTV levels occurred predominantly in patients who were shorter after transplantation (p=0.0001). Conclusion(s): This study shows an association between pre-vaccination TTV load and humoral response to the SARS-CoV-2 vaccine, which correlate with the time after transplantation. We recommend that TTV load measurements are included in further vaccination efficacy studies in immunocompromised cohorts. If the TTV load is indeed a predictor of vaccine response, this could be used as a potential guidance for optimizing vaccination response.

19.
American Journal of Transplantation ; 22(Supplement 3):1095, 2022.
Article in English | EMBASE | ID: covidwho-2063528

ABSTRACT

Purpose: Kidney transplant recipients (KTR) have inadequate responses to 2-dose COVID vaccination schedules and are at increased risk of severe COVID-19. Formation of T cell memory following vaccination is regulated by mTOR complex 1. mTOR inhibitors have been used in pre-clinical models to boost vaccine-elicited cytotoxic T cell memory responses. In observational studies, KTR receiving mTOR inhibitors had improved serological neutralisation and SARS-CoV-2 reactive T cell responses to 2 doses of COVID-19 vaccine, including cytotoxic T cells and circulating T follicular helper cells. We performed a clinical trial in stable KTR using sirolimus as a substitute for mycophenolate prior to a 3rd dose of COVID-19 vaccine to enhance COVID-19 vaccine responses. Method(s): KTR receiving tacrolimus, mycophenylate and corticosteroid with inadequate response to 2 doses of a COVID vaccine (defined by anti-RBD IgG <100U/ mL) and no history of COVID infection were recruited from 2 Australian transplant centres. Patients were randomised in a 1:1 ratio to continue mycophenolate maintenance or switch to sirolimus (trough level target 6 ng/mL). All patients received a 3rd dose of BNT162b2 COVID-19 vaccine and had immunological responses measured 4-6 weeks later. Result(s): 54 patients were randomised to sirolimus switch (n = 28), or control (n = 26). Patients were 70% male, mean age 57.5 years (SD10.4), with mean graft age 6.2 years (SD 5.4). Mean serum trough concentrations of sirolimus and tacrolimus were 6.4 and 6.1 respectively. There have been no safety or tolerability issues in the sirolimus cohort with stable serum creatinine (mean 117.8 vs 119.3, p=0.6), and mild increase in urinary ACR (mean 5.4 vs 17.4, p=0.1). Final results including immunological testing will be collated March 2022. Conclusion(s): Sirolimus switch is safe and well-tolerated. This trial will determine whether the strategy of mTOR inhibitor therapy peri-vaccination can optimise vaccine immune responses against COVID-19 in KTR.

20.
American Journal of Transplantation ; 22(Supplement 3):767, 2022.
Article in English | EMBASE | ID: covidwho-2063510

ABSTRACT

Purpose: Emerging evidence suggests that 3 doses of SARS-CoV-2 mRNA vaccine enhance immunity in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines. Here we report the results of humoral response in KT recipients in comparison with healthy control group after homologous and heterologous regimens with inactivated virus (Coronavac) and mRNA vaccine BNT162b2. Method(s): A multicenter prospective study was conducted. KT recipients received heterologous vaccine schedule (2 doses of Coronavac and a booster of mRNA BNT162b2, n= 136) or homologous (3 doses of BNT162b2 n=19). Healthy control group received 2 doses or Coronavac (n=67) or BNT162b2 (n=15). Serum IgG antibodies against Receptor Binding Domain of SARS-CoV-2 Spike protein were determined 30 and 40 days after last dose. Result(s): Seroconversion was 52.2% and 57,9% with heterologous and homologous vaccination schedules in KT, p=0.789, figure 1. Among KT patients with seroconversion, antibody levels against RBD of SARS-CoV-2 were [1012 (183-3111) and 603 (41-1255) BAU/mL, with heterologous and homologous schedule, respectively. Levels were higher in KT compared to heathy control with 2 doses of inactivated virus 308 (209-335), p=0.03 and lower than heathy control with 2 doses of BNT162b2: 2638 (2608-3808) BAU/mL, p=0.001]. Conclusion(s): Seroconversion improves after a third dose with homologous or heterologous vaccine schedules. Among patients with seroconversion antibody levels were higher than in heathy control with two doses of inactivated virus. Measurement of antibody levels could help to improve vaccination policies.

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