scholarly journals Initial SARS-CoV-2 vaccination response can predict booster response for BNT162b2 but not for AZD1222

2021 ◽  
Author(s):  
Thomas Perkmann ◽  
Nicole Perkmann-Nagele ◽  
Patrick Mucher ◽  
Astrid Radakovics ◽  
Manuela Repl ◽  
...  
Keyword(s):  
Antibody Responses ◽  
Vaccine Response ◽  
Antibody Assay ◽  
Dependent Effect ◽  
Immunosuppressive Medication ◽  
Vaccination Response ◽  
Vaccine Type ◽  
Previous Infection ◽  
Anti Body ◽  
Antibody Levels

Objectives Our objective was to determine whether SARS-CoV-2 antibody levels after the first dose can predict the final antibody response and whether this is dependent on the vaccine type. Methods 69 BNT162b2 (Pfizer/BioNTech) and 55 AZD1222 (AstraZeneca) vaccinees without previous infection or immunosuppressive medication were included. Anti-body levels were quantified 3 weeks after dose 1, in case of AZD1222 directly before boostering (11 weeks after dose 1) and 3 weeks after dose 2, with the Roche SARS-CoV-2 S total antibody assay. Results Pre-booster (BNT162b2: 80.6 [25.5-167.0] BAU/mL, AZD1222: 56.4 [36.4-104.8] BAU/mL, not significant) and post-booster levels (BNT162b2: 2,092.0 [1,216.3-4,431.8] BAU/mL, AZD1222: 957.0 [684.5-1,684.8] BAU/mL, p<0.0001) correlated well in BNT162b2 (ρ=0.53) but not in AZD1222 recipients. Moreover, antibody levels after the first dose of BNT162b2 correlated inversely with age (ρ=-0.33, P=0.013), whereas a positive correlation with age was observed after the second dose in AZD1222 recipients (ρ=0.26, P=0.030). Conclusions In conclusion, our data suggest that antibody levels quantified by the Roche Elecsys SARS-CoV-2 S assay before the booster shot could infer post-booster responses to BNT162b2, but not to AZ1222. In addition, we found a vaccine-dependent effect on antibody responses, suggesting a possible link between vaccine response and vector immunity.

scholarly journals 16 Standardized phytomolecules improve foot and mouth disease vaccine response in grower pigs

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 16-17
Author(s):  
Alexandra Blanchard ◽  
Josselin le Cour Grandmaison ◽  
In Ho Kim ◽  
Yong Min Kim
Keyword(s):  
Foot And Mouth Disease ◽  
Viral Disease ◽  
Mouth Disease ◽  
Vaccine Response ◽  
Blood Samples ◽  
Vaccination Response ◽  
Foot And Mouth ◽  
Negative Effect ◽  
Antibody Titers ◽  
Antibody Levels

Abstract Foot and Mouth Disease (FMD) is a severe viral disease with significant economic impact. In endemic countries, livestock may be vaccinated. Standardized capsicum and turmeric oleoresins have demonstrated a boosting effect of vaccination in broiler, but little is known on their efficacy in swine. The objective of this trial was to evaluate the efficiency of these phytomolecules to improve FMD vaccine response in pigs. Cross-breed pigs (n = 120) with body weight of 24.6 kg were allotted into 3 groups of 40 pigs and assigned into 10 replicates from days 70 to 112 of age. Following treatments were applied: NS: no vaccination; FMD-NS: FMD vaccination; FMD-XT: FMD vaccination + supplementation of XT-N (4% capsicum + 4% turmeric oleoresins, Pancosma, Switzerland) at 125 g/ton in feed. The FMD vaccine (Omanisa + O3039 + A22 Iraq-strain, Merial) was injected at day 78. Blood samples were collected at days 88, 93, 98 and 103 to evaluate antibody levels. Growth performance was evaluated at day 112. Data were analyzed using the GLM procedure of SAS®. During the trial, non-vaccinated pigs (NS) did not display antibody titers against FMD, but vaccinated pigs (FMD-NS and FMD-XT) exhibited significant levels of FMD antibodies (P &lt; 0.05). Pigs of FMD-XT group showed significant higher antibody levels at day 93 (P &lt; 0.05), day 98 (P = 0.06) and day 103 (P &lt; 0.05) in comparison to FMD-NS pigs. It indicated significant improvement of FMD vaccine response in comparison to the vaccinated control. At 112 days, FMD-NS pigs were numerically lighter (53.46 kg) in comparison to non-vaccinated pigs (53.89 kg). However, FMD-XT pigs were heavier (54.51 kg) in comparison to NS pigs (+0.62 kg, P &gt;0.05) and FMD-NS pigs (+1.05 kg, P &lt; 0.05). These findings showed that standardized phytomolecules (XT-N) incorporated into pig diet significantly supported FMD vaccination response and alleviated its negative effect on growth.

scholarly journals Robust antibody responses in 70–80-year-olds 3 weeks after the first or second doses of Pfizer/BioNTech COVID-19 vaccine, United Kingdom, January to February 2021

2021 ◽  
Vol 26 (12) ◽  
Author(s):  
Sathyavani Subbarao ◽  
Lenesha A Warrener ◽  
Katja Hoschler ◽  
Keith R Perry ◽  
Justin Shute ◽  
...  
Keyword(s):  
Immune Response ◽  
United Kingdom ◽  
Single Dose ◽  
Antibody Responses ◽  
Antibody Assay ◽  
Antibody Levels ◽  
Very High

Sera were collected from 185 adults aged ≥ 70 years in London to evaluate the immune response to COVID-19 vaccines. A single dose of Pfizer/BioNtech vaccine resulted in > 94% seropositivity after 3 weeks in naïve individuals using the Roche Spike antibody assay, while two doses produced very high spike antibody levels, significantly higher than convalescent sera from mild-to-moderate PCR-confirmed adult cases. Our findings support the United Kingdom’s approach of prioritising the first dose and delaying the second dose of COVID-19 vaccine.

scholarly journals Reduced BNT162b2 mRNA vaccine response in SARS-CoV-2-naive nursing home residents

2021 ◽  
Author(s):  
David H. Canaday ◽  
Lenore Carias ◽  
Oladayo A. Oyebanji ◽  
Debbie Keresztesy ◽  
Dennis Wilk ◽  
...  
Keyword(s):  
Nursing Home ◽  
Healthcare Workers ◽  
Nursing Home Residents ◽  
Antibody Responses ◽  
Control Measures ◽  
Vaccine Response ◽  
Infection Control Measures ◽  
Data Gap ◽  
Antibody Levels ◽  
Care Worker

AbstractThe SARS-CoV-2 pandemic impact on nursing home (NH) residents prompted their prioritization for early vaccination. To fill the data gap for vaccine immunogenicity in NH residents, we examined antibody levels after BNT162b2 mRNA vaccine to spike, receptor binding domain (RBD) and for virus neutralization in 149 NH residents and 111 health care worker controls. SARS-CoV-2-naive NH residents mount antibody responses with nearly 4-fold lower median neutralization titers and half the anti-spike level compared to SARS-CoV-2-naive healthcare workers. By contrast, SARS-CoV-2-recovered vaccinated NH residents had neutralization, anti-spike and anti-RBD titers similar to SARS-CoV-2-recovered vaccinated healthcare workers. NH residents’ blunted antibody responses have important implications regarding the quality and durability of protection afforded by neoantigen vaccines. We urgently need better longitudinal evidence on vaccine effectiveness specific to NH resident populations to inform best practices for NH infection control measures, outbreak prevention and potential indication for a vaccine boost.

scholarly journals Spike-antibody responses following first and second doses of ChAdOx1 and BNT162b2 vaccines by age, gender, and clinical factors - a prospective community cohort study (Virus Watch)

2021 ◽  
Author(s):  
Madhumita Shrotri ◽  
Ellen Fragaszy ◽  
Cyril Geismar ◽  
Vincent Nguyen ◽  
Sarah Beale ◽  
...  
Keyword(s):  
Cohort Study ◽  
Single Dose ◽  
Antibody Responses ◽  
Solid Organ ◽  
Clinical Factors ◽  
Preventative Measures ◽  
Vaccine Type ◽  
Antibody Titres ◽  
The Uk ◽  
Antibody Levels

Background Vaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the extended dosing interval in the UK, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose. Methods Adults aged 18+ years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike (>=0.8 U/ml), as per the Roche Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors. Results 8,517 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 13,232 samples (8,115 following ChAdOx1, 5,008 following BNT162b2). Seropositivity to Spike was 96.42% (95%CI 96, 96.79) at 28-34 days following a single dose, reaching 99.08% (97.8, 99.62) at 7-14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence of lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men (25.9 vs 42.3 U/ml, p<0.0001), those with a chronic condition (33.0 vs 41.2 U/ml, p<0.0001), diabetes (22.32 vs 36.01 U/ml, p<0.0001), cardiovascular disease (32.1 vs 36.7 U/ml, p=0.0002), or history of cancer (30.1 vs 35.7 U/ml, p=0.0001), particularly those with haematological rather than solid organ cancer (7.48 vs 31.68 U/ml, p<0.0001), and those currently on immunosuppressive therapy (21.7 vs 35.6 U/ml, p<0.0001). Following a second dose, high S-antibody titres (>=250U/ml) were observed for nearly all individuals. Interpretation A single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. However, observed disparities in antibody levels after the first dose by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures such as social distancing, for partially vaccinated adults, particularly those who are older and more clinically vulnerable.

scholarly journals The T-cell clonal response to SARS-CoV-2 vaccination in inflammatory bowel disease patients is augmented by anti-TNF therapy and often deficient in antibody-responders

2021 ◽  
Author(s):  
Dalin Li ◽  
Alexander Xu ◽  
Emebet Mengesha ◽  
Rebecca Elyanow ◽  
Rachel M. Gittelman ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
T Cell Response ◽  
Antibody Responses ◽  
High Antibody ◽  
Cell Responses ◽  
Vaccine Type ◽  
Inflammatory Bowel ◽  
Antibody Levels

AbstractBackgroundVaccination against SARS-CoV-2 is a highly effective strategy to protect against infection, which is predominantly mediated by vaccine-induced antibodies. Postvaccination antibodies are robustly produced by those with inflammatory bowel disease (IBD) even on immune-modifying therapies but are blunted by anti-TNF therapy. In contrast, T-cell response which primarily determines long-term efficacy against disease progression,, is less well understood. We aimed to assess the post-vaccination T-cell response and its relationship to antibody responses in patients with inflammatory bowel disease (IBD) on immune-modifying therapies.MethodsWe evaluated IBD patients who completed SARS-CoV-2 vaccination using samples collected at four time points (dose 1, dose 2, 2 weeks after dose 2, 8 weeks after dose 2). T-cell clonal analysis was performed by T-cell Receptor (TCR) immunosequencing. The breadth (number of unique sequences to a given protein) and depth (relative abundance of all the unique sequences to a given protein) of the T-cell clonal response were quantified using reference datasets and were compared to antibody responses.ResultsOverall, 303 subjects were included (55% female; 5% with prior COVID) (Table). 53% received BNT262b (Pfizer), 42% mRNA-1273 (Moderna) and 5% Ad26CoV2 (J&J). The Spike-specific clonal response peaked 2 weeks after completion of the vaccine regimen (3- and 5-fold for breadth and depth, respectively); no changes were seen for non-Spike clones, suggesting vaccine specificity. Reduced T-cell clonal depth was associated with chronologic age, male sex, and immunomodulator treatment. It was preserved by non-anti-TNF biologic therapies, and augmented clonal depth was associated with anti-TNF treatment. TCR depth and breadth were associated with vaccine type; after adjusting for age and gender, Ad26CoV2 (J&J) exhibited weaker metrics than mRNA-1273 (Moderna) (p=0.01 for each) or BNT262b (Pfizer) (p=0.056 for depth). Antibody and T-cell responses were only modestly correlated. While those with robust humoral responses also had robust TCR clonal expansion, a substantial fraction of patients with high antibody levels had only a minimal T-cell clonal response.ConclusionAge, sex and select immunotherapies are associated with the T-cell clonal response to SARS-CoV-2 vaccines, and T-cell responses are low in many patients despite high antibody levels. These factors, as well as differences seen by vaccine type may help guide reimmunization vaccine strategy in immune-impaired populations. Further study of the effects of anti-TNF therapy on vaccine responses are warranted.

scholarly journals Infliximab is associated with attenuated immunogenicity to BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines in patients with IBD

Gut ◽  
2021 ◽  
pp. gutjnl-2021-324789
Author(s):  
Nicholas A Kennedy ◽  
Simeng Lin ◽  
James R Goodhand ◽  
Neil Chanchlani ◽  
Benjamin Hamilton ◽  
...  
Keyword(s):  
Single Dose ◽  
Primary Outcome ◽  
Geometric Mean ◽  
Antibody Responses ◽  
Antibody Assay ◽  
Past Infection ◽  
White Ethnicity ◽  
Registration Number ◽  
Inflammatory Bowel ◽  
Prior Infection

ObjectiveDelayed second dose SARS-CoV-2 vaccination trades maximal effectiveness for a lower level of immunity across more of the population. We investigated whether patients with inflammatory bowel disease treated with infliximab have attenuated serological responses to a single dose of a SARS-CoV-2 vaccine.DesignAntibody responses and seroconversion rates in infliximab-treated patients (n=865) were compared with a cohort treated with vedolizumab (n=428), a gut-selective anti-integrin α4β7 monoclonal antibody. Our primary outcome was anti-SARS-CoV-2 spike (S) antibody concentrations, measured using the Elecsys anti-SARS-CoV-2 spike (S) antibody assay 3–10 weeks after vaccination, in patients without evidence of prior infection. Secondary outcomes were seroconversion rates (defined by a cut-off of 15 U/mL), and antibody responses following past infection or a second dose of the BNT162b2 vaccine.ResultsGeometric mean (SD) anti-SARS-CoV-2 antibody concentrations were lower in patients treated with infliximab than vedolizumab, following BNT162b2 (6.0 U/mL (5.9) vs 28.8 U/mL (5.4) p<0.0001) and ChAdOx1 nCoV-19 (4.7 U/mL (4.9)) vs 13.8 U/mL (5.9) p<0.0001) vaccines. In our multivariable models, antibody concentrations were lower in infliximab-treated compared with vedolizumab-treated patients who received the BNT162b2 (fold change (FC) 0.29 (95% CI 0.21 to 0.40), p<0.0001) and ChAdOx1 nCoV-19 (FC 0.39 (95% CI 0.30 to 0.51), p<0.0001) vaccines. In both models, age ≥60 years, immunomodulator use, Crohn’s disease and smoking were associated with lower, while non-white ethnicity was associated with higher, anti-SARS-CoV-2 antibody concentrations. Seroconversion rates after a single dose of either vaccine were higher in patients with prior SARS-CoV-2 infection and after two doses of BNT162b2 vaccine.ConclusionInfliximab is associated with attenuated immunogenicity to a single dose of the BNT162b2 and ChAdOx1 nCoV-19 SARS-CoV-2 vaccines. Vaccination after SARS-CoV-2 infection, or a second dose of vaccine, led to seroconversion in most patients. Delayed second dosing should be avoided in patients treated with infliximab.Trial registration numberISRCTN45176516.

scholarly journals Low Immunogenicity of Intravesical Phage Therapy for Urogenitary Tract Infections

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 627
Author(s):  
Sławomir Letkiewicz ◽  
Marzanna Łusiak-Szelachowska ◽  
Ryszard Międzybrodzki ◽  
Maciej Żaczek ◽  
Beata Weber-Dąbrowska ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Bacterial Infections ◽  
Phage Therapy ◽  
Serum Antibody ◽  
Multidrug Resistant ◽  
Antibody Responses ◽  
Urogenital Infections ◽  
Reliable Model ◽  
Tract Infections ◽  
Antibody Levels

Patients with chronic urinary and urogenital multidrug resistant bacterial infections received phage therapy (PT) using intravesical or intravesical and intravaginal phage administration. A single course of PT did not induce significant serum antibody responses against administered phage. Whilst the second cycle of PT caused a significant increase in antibody levels, they nevertheless remained quite low. These data combined with good therapy results achieved in some patients suggest that this mode of PT may be an efficient means of therapy for urogenital infections and a reliable model for a clinical trial of PT.

scholarly journals Pneumococcal Nasopharyngeal Carriage following Reduced Doses of a 7-Valent Pneumococcal Conjugate Vaccine and a 23-Valent Pneumococcal Polysaccharide Vaccine Booster

2010 ◽  
Vol 17 (12) ◽  
pp. 1970-1976 ◽  
Author(s):  
F. M. Russell ◽  
J. R. Carapetis ◽  
C. Satzke ◽  
L. Tikoduadua ◽  
L. Waqatakirewa ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Pneumococcal Conjugate Vaccine ◽  
Polysaccharide Vaccine ◽  
Dose Effect ◽  
Pneumococcal Polysaccharide Vaccine ◽  
Pneumococcal Carriage ◽  
Primary Series ◽  
Vaccine Type ◽  
Vaccine Booster ◽  
Antibody Levels

ABSTRACT This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.

scholarly journals CD4+ CD25+ Regulatory T Cells Modulate the T-Cell and Antibody Responses in Helicobacter-Infected BALB/c Mice

2006 ◽  
Vol 74 (6) ◽  
pp. 3519-3529 ◽  
Author(s):  
Maria Kaparakis ◽  
Karen L. Laurie ◽  
Odilia Wijburg ◽  
John Pedersen ◽  
Martin Pearse ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Bacterial Colonization ◽  
Antibody Responses ◽  
T Helper 1 ◽  
Time Of Infection ◽  
Lymph Node Cells ◽  
Antibody Levels ◽  
And Control

ABSTRACT Gastric Helicobacter spp. induce chronic gastritis that may lead to ulceration and dysplasia. The host elicits a T helper 1 (Th1) response that is fundamental to the pathogenesis of these bacteria. We analyzed immune responses in Helicobacter-infected, normal mice depleted of CD4+ CD25+ T cells to investigate the in vivo role of regulatory T cells (Tregs) in the modulation of Helicobacter immunopathology. BALB/c and transgenic mice were depleted of CD4+ CD25+ T cells by administration of an anti-CD25 antibody either at the time of infection with Helicobacter or during chronic infection and gastritis. Depletion of CD25+ Tregs prior to and during infection of mice with Helicobacter spp. did not affect either bacterial colonization or severity of gastritis. Depletion of CD25+ Tregs was associated with increased Helicobacter-specific antibody levels and an altered isotype distribution. Paragastric lymph node cells from CD25+ Treg-depleted and control infected mice showed similar proliferation to Helicobacter antigens, but only cells from anti-CD25-treated animals secreted Th2 cytokines. CD25+ Tregs do not control the level of gastritis induced by gastric Helicobacter spp. in normal, thymus-intact BALB/c mice. However, CD25+ Tregs influence the cytokine and antibody responses induced by infection. Autoimmune gastritis is not induced in Helicobacter-infected mice depleted of CD25+ Tregs but is induced in CD25+ Treg-depleted mice, which have a higher frequency of autoreactive T cells.

scholarly journals Determinants of Protection Against Measles Infection in a Vaccinated Healthcare Worker

2020 ◽  
Vol 41 (S1) ◽  
pp. s185-s185
Author(s):  
Annie St-Pierre ◽  
Anne-Marie Charron ◽  
Pamela Doyon-Plourde ◽  
Caroline Quach
Keyword(s):  
Vaccination Status ◽  
Secondary Case ◽  
Enzyme Linked Immunosorbent Assay ◽  
Demographic Information ◽  
Vaccine Response ◽  
Vaccine Responses ◽  
Equivocal Result ◽  
Commercial Enzyme Immunoassay ◽  
Antibody Levels ◽  
Care Worker

Background: In 2019, a measles community outbreak resulted in a secondary case in a health care worker (HCW) working in a pediatric hospital in Montral, Canada. Following the event, HCWs were screened to identify individuals susceptible to measles infection based on serology results. Objective: Our aim was to assess measles seroprotection rates and to evaluate vaccine responses of susceptible HCWs using commercial enzyme immunoassay (EIA) or enzyme linked immunosorbent assay (ELISA). Methods: Emergency department (ED) employees, including doctors, were screened for measles susceptibility as part of a postoutbreak measure by the hospital occupational health service. Demographic information was collected. Measles history and vaccination information were collected using a personal vaccination booklet, employee vaccination profile, or the Qubec vaccination registry. According to the Quebec Immunization Protocol (PIQ), individuals born before 1970, or who have received 2 doses of a measles-containing vaccines are considered protected. Individuals with undetectable or equivocal antibody levels were considered at risk of measles infection. These individuals were offered vaccination and were tested for vaccine response 4 weeks after vaccination. Results: Anti-IgG measles antibody results, demographic information, and vaccination information were obtained for 257 employees. The results are currently available for 233 HCWs: 224 HCWs (96%) were seropositive, 7 (3%) were seronegative, and 2 were equivocal. Among seronegative individuals, 6 (85.7%) were born after 1980 and 3 (42.9%) had received 2 doses of a measles-containing vaccine. Of those with an equivocal result, 1 (50%) had received 2 doses and 1 (50%), born after 1970, did not confirm vaccination status. Finally, 9 (4%) of seropositive individuals were not vaccinated; of whom 8 (88.9%) were born before 1970. Conclusions: Our preliminary results suggest that the 95% immunity threshold that is usually required to prevent secondary transmission of measles has been reached in our ED HCW cohort. Even years after the second MMR dose, HCWs remain well protected. Relying on documented vaccination status is thus acceptable.Funding: NoneDisclosures: None

Sign in / Sign up

Export Citation Format

Share Document