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1.
Gastroenterology ; 162(7):S-1252, 2022.
Article in English | EMBASE | ID: covidwho-1967441

ABSTRACT

Introduction We sought to evaluate the longitudinal serological response from the second to third dose of SARS-CoV-2 vaccine in liver transplant recipients at our institution. This study is ongoing and the total N will increase. Methods We prospectively enrolled 54 LT patients who received Pfizer-BioNTech or Moderna vaccine in two doses 3-4 weeks apart at our institution and an additional third dose after CDC approval in August 2021. 6 patients were excluded because of a positive nucleocapsid Ab after the third dose that indicated prior COVID infection. Recipients had semi-quantitative spike IgG and nucleocapsid IgG titers tested between 30 and 75 days after receiving a second vaccine dose. Serological responses to both spike and nucleocapsid antigens indicated COVID-19 infection. All recipients had spike and nucleocapsid Ab titers checked at least 14 days after receiving the third dose. Recipients who had a positive spike Ab titer and negative nucleocapsid titer after a second vaccine dose had repeat spike and nucleocapsid Ab testing within 1 week prior to receiving their third vaccine dose. Results Among 48 LT recipients that met inclusion criteria, seropositivity for spike Ab increased from 47.9% after the second dose to 81.3% after the third dose. 9 patients who were seronegative after a third dose had failed to develop detectable spike Ab after their second dose. The median interval between the second and third doses was 5.9 months. After the third dose, 69% of seropositive recipients had a high spike Ab titer. In 25 recipients who were seronegative after a second dose, 64% produced spike Abs after their third dose. Recipients who remained seronegative after 3 vaccine doses had significantly higher mean tacrolimus trough concentrations. To assess whether spike Ab titers waned after the second vaccine dose, we retested spike Ab titers within one week prior to the third dose in 14 out of 23 recipients who were seropositive after their second dose. All 14 patients had a decline in their spike Ab titers after their second dose. Previously detectable spike Ab titers became undetectable in 5 recipients. However, all five of these patients regained detectable spike Ab after the third vaccine. Discussion We demonstrate that a third dose of mRNA SARS-CoV-2 vaccine in LT recipients was effective. Minimizing immunosuppression by lowering tacrolimus trough thresholds is one potential strategy to improve immune responses. Our results also provide useful information about the optimal interval between the second and third vaccine doses in SOT recipients. Our cohort received the third vaccine dose after a longer delay of 6 months. With this delay, we demonstrated higher seropositivity and seroconversion rates than those reported after shorter interval dosing. A shorter delay between doses is a practical approach to help mitigate the immediate risk in this population. (Table Presented)

2.
Gastroenterology ; 162(7):S-1006, 2022.
Article in English | EMBASE | ID: covidwho-1967392

ABSTRACT

BACKGROUND Little is known about the impact of immunosuppressants on COVID-19 vaccination in patients with immune-mediated inflammatory diseases (IMID). Although humoral response may be attenuated in patients using immunomodulators (IMM) and TNFinhibitors (anti-TNF), data regarding cellular response are scarce and conflicting. This study was aimed to identify immune response to COVID-19 vaccination in IMID patients. METHODS A prospective observational multicentre cohort study was conducted to examine the immunogenicity of mRNA vaccines to SARS-CoV-2 in adult IMID patients using immunosuppressive therapy (anti-TNF, IMM, anti-TNF+IMM, anti-IL12/23, anti-IL-17, anti-IL-23) or no therapy as compared to healthy controls (HC). Patient details and vaccination history were recorded. Blood samples were drawn at 3 time points: before, 3-4 weeks after first and 2 weeks after second vaccination. Humoral immune response to S and RBD proteins were assessed by ELISA. Neutralization was tested against 4 variants of SARS-CoV-2 by surrogate neutralization ELISA. Cellular immune responses were determined based on analysis of 9 secreted cytokines and cytotoxic molecules after stimulation of PBMC with S peptide pools. Response to N protein was used to assess SARS-CoV-2 exposure. RESULTS A total of 159 subjects (133 IMID patients and 26 HC) were included in this study (median age 42 years [IQR 30-53], 52% male). Of 133 IMID patients, 87 had inflammatory bowel disease, 23 psoriatic arthritis, 18 psoriasis, 11 ankylosing spondylarthritis and 4 rheumatoid arthritis. Of these, 44 used anti-TNF, 9 IMM, 18 anti-TNF+IMM, 33 anti-IL-12/23, 9 anti-IL-17, 10 anti-IL-23 therapy and 10 no therapy. All subjects received 2 doses of mRNA vaccines (2x Pfizer, 2x Moderna or mixed) between December 2020 and September 2021. The vast majority of subjects had minimal binding antibody and T cell responses to N, indicating they were COVID-19 naïve. After dose 1, anti-TNF group had lower IL-2 vs untreated IMID (p<0.01), and the anti-IL-23 group had lower IFN-g vs HC (p<0.01), though there was wide variation in responses within groups. Following dose 2, median responses between groups were mostly similar, but antibody responses were significantly lower in patients on anti-TNF as compared to HC in subjects that received two doses of Pfizer (p=0.01). Pooled data for all subjects combined show a higher response to Moderna over Pfizer in ELISA, neutralization and T cell readouts, and a lower response for those over 60 years of age after dose 2. Longer follow-up is in process to monitor the durability of these responses over time and after third dose. CONCLUSION Immune responses after 2 doses of mRNA vaccines in immunocompromised IMID patients largely reach the level of that of HC albeit antibody responses in the anti-TNF group are weaker and with wide variability between subjects within some groups

3.
Gastroenterology ; 162(7):S-1005, 2022.
Article in English | EMBASE | ID: covidwho-1967390

ABSTRACT

Background: Immune responses to the SARS-CoV-2 vaccination may be influenced by immunomodulatory drugs (IMDs). We investigated the immune responses and safety in fully vaccinated Japanese patients with IBD. Subjects and Methods: IBD patients and control subjects at 39 institutes were invited to participate in the study from March to October 2021. Blood sample collections to measure anti-SARS-CoV-2 spike IgG antibody titers were planned pre-1st vaccination, pre-2nd vaccination, and at 4 weeks, 3 months and 6 months post-2nd vaccination. Immune responses were compared between groups, considering baseline characteristics and IMD treatments. (UMIN000043545) The interim analyses presented here include mainly data from the 4-weeks post-2nd vaccination time-point. Results: In total, 679 IBD patients and 203 controls were enrolled (Table 1). The IBD group received the BNT162b2 vaccine (86.2%) and the mRNA-1273 vaccine (12.5%), and the control group received the BNT162b2 vaccine (86.9%) and the mRNA-1273 vaccine (12.1%). Only 4 cases (0.7%) in the IBD group and 2 (1.0%) in the control group were infected with COVID-19. Adverse events of 2nd vaccination occurred in 48.4% of the IBD group and 35.1% of the control group. Comparison between administrated and non-administrated IBD patients for each IMD revealed an attenuated genomic mean titer (GMT [U/mL]) in those taking systemic steroids (18.85 vs 31.24), anti-TNF monotherapy (28.31 vs 42.99), anti- TNF therapy+ immunomodulator (IM) (12.86 vs 35.26), vedolizumab+IM (19.49 vs 30.39), ustekinumab+IM (20.44 vs 30.79), and tofacitinib (9.54 vs 32.08), but not in those taking oral 5-ASA (29.50 vs 32.40), or vedolizumab (41.85 vs 40.20) and ustekinumab (55.56 vs 39.26) monotherapies. Estimated least square means of the GMT by a multiple linear regression model are shown in Table 2. GMTs were significantly influenced by increasing age and allergy (51.2, 95%CI 42.1-62.3;p=0.0293), and tended to be influenced by COVID- 19 infection (139.1, 41.0-472.2;p=0.0572). Sex, smoking, drinking, IBD, and adverse events of 2nd vaccination did not affect the GMT. The GMT was significantly higher for mRNA- 1273 (90.3 [60.8-134.1]) than for BNT162b2 (39.6 [35.2-44.6], p= 0.0001). Systemic steroids (22.9 [13.9-37.7], p=0.0119), IM (24.2 [18.7-31.4], p<0.0001), anti-TNF agents (20.8 [15.3-28.3], p<0.0001), vedolizumab (25.2 [15.0-42.2], p=0.0409), ustekinumab (28.9 [18.5-45.0], p=0.0754), and tofacitinib (5.5 [2.8-10.9], p<0.0001), but not oral 5- ASA (39.1 [31.9-47.9], p=0.3225), attenuated GMTs at 4 weeks post-2nd vaccination (Table 2). Conclusion: Aging and most IMD options attenuated immunogenicity in fully vaccinated IBD patients. Prioritization of a booster vaccination should be considered for IBD patients treated with IMDs. (Table Presented) (Table Presented)

4.
Gastroenterology ; 162(7):S-652, 2022.
Article in English | EMBASE | ID: covidwho-1967353

ABSTRACT

Introduction: Patients with inflammatory bowel disease (IBD) treated with anti-TNF therapy exhibit attenuated humoral immune responses to vaccination against SARS-CoV-2. The gut microbiota and its functional metabolic output, which are perturbed in IBD, play an important role in shaping host immune responses. We explored whether the gut microbiota and metabolome could explain variation in anti-SARS-CoV-2 vaccination responses in immunosuppressed IBD patients. Methods: Faecal and serum samples were prospectively collected from patients with IBD established on infliximab therapy (for >12 weeks) who were undergoing vaccination against SARS-CoV-2. The Roche Elecsys Anti-SARS-CoV-2 spike (S) and nucleocapsid (N) immunoassays were used to measure antibody responses following two doses of either ChAdOx1 nCoV-19 or BNT162b2 vaccine. Seroconversion was defined by a cut-off anti-S concentration of 15 U/ml, which correlated with 20% viral neutralization;anti-S antibody concentration of < 380 U/ml was indicative of poor response to vaccination. Patients with serological evidence of prior SARS-CoV-2 infection were excluded from the analysis. Faecal calprotectin measurement, 16S rRNA gene amplicon sequencing, nuclear magnetic resonance (NMR) spectroscopy and bile acid profiling with ultra-performance liquid chromatography mass spectrometry (UPLC-MS) were performed on faecal samples. Results: Forty-five infliximab-treated patients were recruited (median age 40 [range 19-67];32 Crohn's disease, 13 ulcerative colitis;28 with concomitant immunomodulator therapy;six with prior infection). 14 patients (35%) had seroconverted after one dose of vaccine and 37 (95%) seroconverted after two doses. 18 patients (46%) had a poor response after two doses of vaccine. There was no association between faecal calprotectin and vaccine response (p=0.41). No differences between satisfactory and poor vaccine responders were noted in alpha or beta diversity of the gut microbiota. The faecal metabolome of satisfactory responders was enriched in the microbial metabolite trimethylamine (q=0.03). Trends were noted linking the short chain fatty acid butyrate with satisfactory response (P=0.01) and succinate with poor response (P=0.06). No significant differences in primary or secondary bile acids were found to associate with vaccine response. The butyrate-producing genus Roseburia was positively correlated with faecal butyrate abundance (q=0.03). Conclusion: Our data suggest an association between gut microbiota function and variable serological response to vaccination against SARS-CoV-2 in immunocompromised patients. Microbial metabolites including trimethylamine and butyrate may be important in mitigating anti-TNF-induced attenuation of the immune response.

5.
Gastroenterology ; 162(7):S-278-S-279, 2022.
Article in English | EMBASE | ID: covidwho-1967265

ABSTRACT

Background: Human-associated microbial communities have been linked to host immune response to respiratory viral infections. Prior investigations have observed shifts in the composition of the gut or respiratory microbiome in severe COVID-19. However, there has been no comprehensive metagenomic evaluation of the interaction between lower respiratory and gut microbiomes and host immune factors in COVID-19. Methods: From April 2020 to May 2021, we prospectively enrolled 153 hospitalized patients with mild (n=12), moderate (n=65), and severe (n=76) COVID-19 infection categorized using established clinical criteria. We longitudinally collected stool (n=270) for metagenomic profiling, and in a subset, we generated comprehensive host-microbiome-molecular profiles by collecting sputum metagenomes (n=87 participants with 212 samples) and blood cytokine levels (n=109 with 181 samples) weekly until hospital discharge. We performed omnibus testing of overall gut and respiratory community structure, species-level differential abundance testing using mixed effects modeling accounting for repeated sampling, hierarchical clustering of paired gut and respiratory metagenomic profiles, and multi-omic machine learning classification of disease severity. Results: Patients with severe COVID-19 tended to be older, were more frequently male, had higher rates of overweight/obesity, and a greater mean Charlson Comorbidity Index. Patients with severe COVID-19 infection had significantly decreased stool and respiratory microbiome a-diversity irrespective of antibiotic administration. COVID severity accounted for a small proportion of variance in stool (R2=2.4%, p=0.002) and sputum (R2=4.4%, p= 0.03) profiles. Hierarchical clustering of paired gut and respiratory samples from patients with severe COVID revealed the joint expansion of oral-typical taxa typically present during systemic inflammation (i.e., increases in Streptococcus and Peptostreptococus spp. in both gut and sputum). A pro-inflammatory milieu defined by a composite elevation of circulating plasma cytokines (e.g., IL-6, TNF-a, and IL-29 among others) were linked to broad microbial excursions in community structure for both stool and sputum as measured by Bray-Curtis distances. A random forest classifier incorporating either stool or sputum taxonomic features and accounting for age, sex, body mass index, and recent antibiotic use achieved excellent classification of biospecimens from patients with severe vs. non-severe COVID patients (AUROC > 0.80). Conclusions: Alterations of the gut and respiratory microbiome were associated with differences in host immune response and COVID-19 disease severity. Further studies are needed to identify the potential role of human-associated microbial communities as a biomarker for poor patient outcomes in COVID-19 who may warrant escalated levels of care.(Figure Presented) Fig. 1. (A) Using unsupervised feature selection (species abundance > 0.001) inclusive of taxa differentially abundant by non-parametric Wilcoxon rank-sum testing (nominal p-value < 0.05), (B) we performed random forest classification using a twice-repeated 5-fold crossvalidation scheme to predict COVID-19 disease severity from shotgun metagenomic stool profiles (C) yielding an AUROC of 0.91.

6.
Gastroenterology ; 162(7):S-160, 2022.
Article in English | EMBASE | ID: covidwho-1967250

ABSTRACT

Background: Vaccine-induced protection against SARS-CoV-2 infection is predominantly mediated by humoral immunity;protection against disease progression is primarily determined by cellular immunity. Patients with inflammatory bowel disease (IBD) have high rates of post-vaccination anti-Spike IgG [IgG(S)] seroconversion, but postvaccination immune responses relative to non-IBD controls have not been well described. We aimed to assess post-vaccination humoral (antibody) and cellular (T-cell) responses in IBD relative to healthcare worker (HCW) controls. Methods: We evaluated IBD patients enrolled in a US registry referred from 26 centers at 2, 8, and 16 weeks after completing 2 doses of SARSCoV- 2 mRNA vaccination and compared results to non-IBD non-immunosuppressed HCW participating in a parallel study. We analyzed plasma antibodies to the receptor binding domain of the viral spike protein using the SARS-CoV-2 IgG-II assay (Abbott Labs, Abbott Park, IL);IgG(S) > 50 AU/mL was defined as positive. Those with prior COVID were excluded. We also performed T-cell clonal analysis by T-cell receptor (TCR) immunosequencing at 8 weeks (Adaptive Biotechnologies, Seattle, WA). 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. Analyses were adjusted for age, sex and vaccine type. Results: Overall, 1805 subjects were included (IBD n=1074 (65% Crohn's disease, 35% ulcerative colitis);HCW n=731). Age and sex were similar between both cohorts;Hispanic ethnicity and Asian race were less common among IBD than HCW (Table). Vaccine type included BNT162b2 (Pfizer) (75% of IBD, 98% of HCW) and the remainder mRNA-1274 (Moderna). IBD treatments included anti- TNF (46%), other biologics (33%), other immune suppressing therapy (9%), and no immune suppression (12%). Postvaccination antibody levels were lower among IBD than HCW both before and after adjusting for vaccine type (p<0.0001 each timepoint;Figure). After further restricting the IBD cohort to those on no immune-suppressive therapies, antibodies remained lower in IBD vs HCW at 2w (p=0.008) and 8w (p<0.0001), but not 16w (p=0.07). Among 321 subjects with available whole cell samples at 8 weeks (IBD n=163, HCW =158), Spikespecific TCR responses were similar between IBD and HCW for both clonal breadth and depth in both unadjusted and adjusted analyses;sub-analyses of those on biologics yielded similar results. Conclusion: Patients with IBD have dampened humoral responses, but similar cellular responses, after SARS-CoV-2 mRNA vaccination relative to HCW. These findings suggest a potentially greater risk of infection, but not of disease progression, among those with IBD, and should be considered to help guide booster dosing strategies for the IBD population. (Figure Presented) (Figure Presented) Figure: Post-vaccination immune responses: (A) Antibody responses are lower in IBD relative to non-IBD healthcare workers at 2, 8, and 16 weeks (p<0.0001 at each timepoint). In contrast, post-vaccination Spike-specific T-cell receptor clonal breadth (B1) and clonal depth (B2) at 8 weeks are similar in IBD compared to healthcare workers.

7.
Gastroenterology ; 162(7):S-68-S-69, 2022.
Article in English | EMBASE | ID: covidwho-1967239

ABSTRACT

Introduction: Gut dysbiosis is associated with immune dysfunction and severity in COVID- 191-2. This study aimed to determine targeting dysbiosis as a therapy and its effect on antibody formation, gut dysbiosis and immune profile in patients with COVID-19. Material & Methods: In an open-label study, 25 consecutive hospitalized patients with COVID- 19 received a novel microbiome immunity formula (SIM01) for 28 days;30 patients who did not receive the intervention acted as controls. We collected fecal and blood samples at baseline and week 5 and followed subjects from admission up to five weeks. We performed multi-omics analysis using data from peripheral blood mononuclear cell (PBMC) transcriptome, fecal metagenomic sequencing and fecal metabolomic profiling (Figure 1A). Results: Significantly more COVID-19 patients on SIM01 developed anti-SARS-CoV-2 IgG than the control group at 2 weeks (Figure 1B). Patients on SIM01 (but not controls) showed a significant reduction of plasma levels of interleukin (IL)-6, macrophage colony-stimulating factor (M-CSF), tumour necrosis factor (TNF-a), IL-1RA (Figure 1C) and downregulated COVID-19 related signalling pathway in PBMC at Week 5. Fecal samples of subjects on SIM01 were enriched in commensal bacteria and reduced in opportunistic pathogens at week 4 and 5. Elevated plasma acetic acid in SIM01 group showed a negative correlation with SARS-CoV-2 viral load in nasopharyngeal samples (Figure 2A). Increased relative abundance of Bifidobacteria adolescentis and Coprococcus comes in fecal samples in SIM01 group positively correlated with plasma acetic acid levels (Figure 2B). Conclusion: We showed for the first time a novel microbiome formula SIM01 was effective in hastening antibody formation against SARS-CoV-2, reduced pro-inflammatory immune markers and restored gut dysbiosis in hospitalised COVID-19 patients. References: 1. Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology 2020;159:944-955 e8. 2. Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID- 19. Gut 2021;70:698-706. (Figure Presented) (Figure Presented)

8.
Open Respiratory Archives ; 4(3), 2022.
Article in English | EMBASE | ID: covidwho-1966975
9.
Journal of Reproductive Immunology ; : 103685, 2022.
Article in English | ScienceDirect | ID: covidwho-1966885

ABSTRACT

Breast milk is a pivotal source to provide passive immunity in newborns over the first few months of life. Very little is known about the levels of transfer of antibodies over the period of breastfeeding. We conducted a prospective study in which we evaluated concentrations of anti-SARS-CoV-2 Spike IgA and RBD IgG/M/A antibodies in maternal serum and breast milk over a duration of up to 6 months after delivery. We compared antibody levels in women with confirmed COVID-19 infection during pregnancy (n=16) to women with prenatal SARS-CoV-2 vaccination (n=5). Among the recovered women, n=7 (44%) had been vaccinated during the lactation period as well. We observed intraindividual moderate positive correlations between antibody levels in maternal serum and breast milk (r=0.73, p-value<0.0001), whereupon the median levels were generally higher in serum. Anti-RBD IgA/M/G transfer into breast milk was significantly higher in women recovered from COVID-19 and vaccinated during lactation (35.15AU/ml;IQR 21.96- 66.89AU/ml) compared to the nonvaccinated recovered group (1.26AU/ml;IQR 0.49- 3.81AU/ml), as well as in the vaccinated only group (4.52AU/ml;IQR 3.19- 6.23AU/ml). Notably, the antibody level in breast milk post SARS-CoV-2 infection sharply increased following a single dose of vaccine. Breast milk antibodies in all groups showed neutralization capacities against an early pandemic SARS-CoV-2 isolate (HH-1) and moreover, also against the Omicron variant, although with lower antibody titer. Our findings highlight the importance of booster vaccinations especially after SARS-CoV-2 infection in pregnancy in order to optimize protection in mother and newborn.

10.
Enfermedades Infecciosas y Microbiologia ; 41(2):73-80, 2021.
Article in Spanish | EMBASE | ID: covidwho-1965521

ABSTRACT

introduction. hla alleles play a fundamental role in the development of the immune response against viral infections. objective. Gather the information available on the association of different hla alleles with increased protection or susceptibility;furthermore, the impact on complications associated with sars-cov-2 infection. methodology. An information search was carried out in the Scopus, PubMed/Medline, lilacs and Academic Google databases that answered the research question: What is the association between hla and sars-cov-2 infection and the severity of the illness? Records of clinical trials from the databases of the who International Clinical Trials Platform were included. results. It was found that the hla-a* 25: 01, hla-b* 46: 01 and hla-c* 01: 02 alleles were associated with greater susceptibility to infection, while the hla-a* 02: 01 alleles, hla-a* 24: 02 and hla-b*27: 07 were associated with greater severity of the disease and the alleles hla-a* 02: 02, hla-b* 15: 03 and hla-c* 12: 03 as protective factor in covid-19. conclusions. The association between susceptibility, protection and severity with the different types of hla are mainly reported in silico analysis, and its precision is limited, requiring support based on in vitro and in vivo experimental studies and clinical trials in different populations. A greater focus is needed on the affinity of the various hla alleles by the sars-cov-2 proteome to elucidate the immunopathogenesis of the disease.

11.
Vaccine ; 2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1967208

ABSTRACT

Mass vaccination against the disease caused by the novel coronavirus (COVID-19) was a crucial step in slowing the spread of SARS-CoV-2 in 2021. Even in the face of new variants, it still remains extremely important for reducing hospitalizations and COVID-19 deaths. In order to better understand the short- and long-term dynamics of humoral immune response, we present a longitudinal analysis of post-vaccination IgG levels in a cohort of 166 Romanian healthcare workers vaccinated with BNT162b2 with weekly follow-up until 35 days past the first dose and monthly follow-up up to 6 months post-vaccination. A subset of the patients continued with follow-up after 6 months and either received a booster dose or got infected during the Delta wave in Romania. Tests were carried out on 1694 samples using a CE-marked IgG ELISA assay developed in-house, containing S1 and N antigens of the wild type virus. Participants infected with SARS-CoV-2 before vaccination mount a quick immune response, reaching peak IgG levels two weeks after the first dose, while IgG levels of previously uninfected participants mount gradually, increasing abruptly after the second dose. Overall higher IgG levels are maintained for the previously infected group throughout the six month primary observation period (e.g. 36-65 days after the first dose, the median value in the previously infected group is 5.29 AU/ml, versus 3.58 AU/ml in the infection naïve group, p less than 0.001). The decrease of IgG levels is gradual, with lower median values in the infection naïve cohort even 7-8 months after vaccination, compared to the previously infected cohort (0.7 AU/ml versus 1.29 AU/ml, p = 0.006). Administration of a booster dose yielded higher median IgG antibody levels than post second dose in the infection naïve group and comparable levels in the previously infected group.

12.
Vaccine ; 2022 Jul 27.
Article in English | MEDLINE | ID: covidwho-1967204

ABSTRACT

BACKGROUND: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has proven to be a successful strategy for prevent severe infections. CoronaVac and BNT162b2 are the most used vaccines worldwide, but their use in heterologous vaccination schedules is still subjected to evaluation. METHODS: Fifty healthy individuals who received heterologous prime-boost vaccination with CoronaVac and BNT162b2 were enrolled in a post-vaccination serological follow-up longitudinal prospective study. We evaluated specific serum anti-receptor binding domain (RBD) IgG antibody levels, and their capacity to block RBD-ACE2 interaction with a surrogate neutralization assay. In 20 participants, we assessed antibody binding kinetics by surface plasmon resonance, and Fc-mediated functions by ADCC and ADCP reporter assays. RESULTS: Our baseline seronegative cohort, displayed seroconversion after two doses of CoronaVac and an important decrease in serum anti-RBD IgG antibodies levels 80 days post-second dose. These levels increased significantly early after the third dose with BNT162b2, but 73 days after the booster we found a new fall. Immunoglobulin functionalities showed a similar behavior. CONCLUSIONS: The heterologous prime-boost vaccination with CoronaVac and BNT162b2 generated an impressive increase in serum anti-RBD specific antibody levels followed by a drop. Nevertheless, these titers remained well above those found in individuals only vaccinated with CoronaVac in the same elapsed time. Serum IgG levels showed high correlation with antibody binding analysis, their capacity to block RBD-ACE2 interaction, and Fc-effectors mechanisms. Our work sheds light on the humoral immune response to heterologous vaccination with CoronaVac and BNT162b2, to define a post-vaccination correlate of protection against SARS-CoV-2 infection and to discuss the scheduling of future vaccine boosters in general population.

13.
Int J Surg ; 104: 106806, 2022 Aug 02.
Article in English | MEDLINE | ID: covidwho-1966637
14.
Epidemiologiya i Vaktsinoprofilaktika ; 21(1):61-66, 2022.
Article in Russian | Scopus | ID: covidwho-1965076

ABSTRACT

Relevance. Active mass vaccination of the population against a new COVID-19 is being carried out on the territory of the Russian Federation, which is recognized as a priority strategy for the country's healthcare for the near and long-term periods. One of the main risk groups that are subject to priority vaccination is medical workers. Aims. To evaluate the effectiveness of vaccination of medical organizations ' employees against COVID-19 based on the results of a 6-month prospective follow-up. Materials and methods. The observation group consisted of 356 employees of a medical organization who were vaccinated against COVID-19 with the drug «Gam-Covid-Vac» from December 2020 to April 2021. The effectiveness of vaccination of employees was evaluated by the coefficient of IgG positivity to SARS-CoV-2 by solid-phase enzyme immunoassay 3 weeks after the first administration and 3–4 weeks after the second administration of the vaccine and then 1 time per month. Employees who were revaccinated after 5–6 months. After the initial vaccination, they were examined 10–14 days after the introduction of the first component «Gam-CovidVac». A total of 1921 serum samples were studied. A specific T-cell immune response was determined in two study participants without seroprotection after administration of two components of the «Gam-Covid-Vac» vaccine and eight employees with the elimination of IgG antibodies 4–5 months after vaccination using ELISPOT technology. In addition, 92 blood serum samples of 32 employees from the observation group were examined for specific antibodies to adenovirus by indirect enzyme immunoassay. From December 2020 to June 2021, the study participants were subjected to dynamic clinical observation, once a week they were examined by PCR to detect SARS-CoV-2 RNA in smears from the pharynx and nose (a total of 5696 samples). Results. After the completed course of immunization, the formation of both a humoral (in 99.4% of cases) and cellular immune response (100% among the studied samples) was confirmed. In the next 6 months after vaccination, cases of coronavirus infection were registered in 4.8% of those vaccinated, including 1 person – in the first month after vaccination and 16 – 3–5 months after vaccination. In all cases, the disease occurred in the form of an acute respiratory infection of mild or moderate severity and was characterized by a shorter period of virus isolation compared to similar data on the persistence of the virus in unvaccinated patients (15 days in vaccinated compared to 22 days in unvaccinated). It was found that the presence of immunity to adenovirus infection during vaccination with the drug «Gam-Covid-Vac» did not affect the possibility of forming an immune response to COVID-19. In the group of persons re-vaccinated with the first component of «Gam-Covid-Vac» after 5–6 months. after the initial vaccination, an immune response was received during the follow-up period. Conclusion. Thus, according to the results of the study, a high immunological and epidemiological effectiveness of vaccination against COVID-19 with the drug «Gam-Covid-Vac» was established in a group of medical workers, and the effectiveness and safety of the administration of a booster dose of the vaccine after primary vaccination was also shown. Keywords: coronavirus infection, COVID-19, vaccination, «Gam-Covid-Vac», medical workers, humoral and cellular immune response No conflict of interest to declare. © 2022, Numikom. All rights reserved.

15.
International Journal of Advanced Biological and Biomedical Research ; 10(1):18-31, 2022.
Article in English | GIM | ID: covidwho-1964939

ABSTRACT

Background: Coronavirus disease 2019 (COVID-19) is a pandemic caused by a novel coronavirus. On 30 January 2020, the first case of the COVID-19 was reported in India and it affects the whole world. The impact of various nutrients on the human immune system. To defend itself, the human body has numerous components. The human immune system identifies molecules that are foreign to its structure and responds to them in a useful manner. When a pathogen factor enters the human body, the immune system responds by triggering an immunological response.

16.
Italian Journal of Gender-Specific Medicine ; 8(2):105-111, 2022.
Article in English | Scopus | ID: covidwho-1963179

ABSTRACT

The coronavirus disease 19 (COVID-19) pandemic is a major challenge for all healthcare systems, as well as for social stability and the economy. The clinical spectrum of COVID-19 is: asymptomatic;mild to moderate;severe;and critical disease, leading to different fatality rates. Although countless studies have been published to better understand the pathophysiology of this infectious disease, the mecha-nisms of action of the virus, and the immunological respons-es, further research is needed to unravel the precise host factors determining COVID-19 susceptibility and severity. A considerable interest from the media and the general public has focused on the disproportionately high COVID-19-re-lated mortality in men. This sex discrepancy may be attrib-uted to biological, genetic and lifestyle differences between males and females, since sex is one of the variables affecting innate and adaptive immune responses, resulting in sex-specific outcomes in patients with infectious and autoim-mune disorders. Therefore, in this paper we will review the available data on sex-and gender-related differences in COVID-19 susceptibility and severity. © 2022, Il Pensiero Scientifico Editore s.r.l.. All rights reserved.

17.
Front Immunol ; 13: 851765, 2022.
Article in English | MEDLINE | ID: covidwho-1963441

ABSTRACT

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), has caused a global crisis. Patients with COVID-19 present with a range of clinical manifestations, from no symptoms to severe illness. However, little is known about the profiles of immune cells required to protect against SARS-CoV-2. This study was performed to determine the immune cells profiles in the peripheral blood of COVID-19 patients with moderate to severe disease (n=52), and compare the findings with those from healthy subjects vaccinated with Pfizer BioNTech mRNA vaccine (VS) (n=62), and non-vaccinated healthy subjects (HS) (n=30) from Kuwait. Absolute counts and percentages of total lymphocytes and lymphocyte subsets (CD3+ T cells, CD4+ T cells, CD8+ T cells, CD19+ B cells, and CD16+CD56+ NK cells) in the peripheral blood of the three groups were analyzed using flow cytometry. The results showed that the absolute counts of total lymphocytes, CD3+, CD4+, and CD8+ T cells, CD19+ B cells, and CD56+ NK cells, were significantly lower in COVID-19 patients than normal healthy controls and vaccinated subjects. The percentages of CD3+ and CD4+ T lymphocytes were also significantly lower in the COVID-19 patients. However, the percentage of CD16+CD56+ NK cells was significantly higher in the peripheral blood of COVID-19 patients, compared to the HS and VS groups with no detectable differences in the percentages of CD8+ T cells and CD19+ B cells between the three groups. Analysis of the monocyte subsets has showed a significantly higher percentage of CD14+HLA-DR+ monocytes in COVID-19 patients compared to HS whereas the inflammatory CD14+CD16+ HLA-DR+ monocytes, and the non-classical CD16+HLA-DR+ monocytes showed significantly lower frequency in the blood of the patients than that of HS. These findings demonstrate perturbations of both innate and adaptive immune cell subsets that reflect dysregulated host responses in COVID-19 patients with moderate to severe disease.


Subject(s)
COVID-19 , COVID-19/prevention & control , HLA-DR Antigens , Healthy Volunteers , Humans , SARS-CoV-2 , Vaccination , Vaccines, Synthetic , mRNA Vaccines
18.
Front Immunol ; 13: 848961, 2022.
Article in English | MEDLINE | ID: covidwho-1963440

ABSTRACT

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results help us to understand the host response to vaccination of CoronaVac and highlight the utility of a systems biology approach in defining molecular correlates of protection to vaccination.


Subject(s)
COVID-19 , Viral Vaccines , Adaptive Immunity , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Phenylalanine , Proteomics , SARS-CoV-2 , Vaccines, Inactivated
19.
Cent Eur J Public Health ; 30(2): 111-118, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1964910

ABSTRACT

OBJECTIVES: Understanding immune response is critical for control of COVID-19 pandemic. However, recent studies show that vaccine-induced humoral immunity may not be long-lasting and weaker in SARS-CoV-2 variants of concern. METHODS: In May 2021, 253 self-nominated persons were tested for antibodies against SARS-CoV-2 in 1 to 104 days (mean 41, median 28) after two doses of Moderna and Pfizer-BioNTech vaccines in the city of Brno, Czechia. Two point-of-care iCHROMA™ II immunofluorescence assays were used: COVID-19 Ab against mix of SARS-CoV-2 nucleocapsid and spike proteins (IgG Ab); and COVID-19 nAb against S1-RBD protein (nAb). Results were analysed in relation to gender, age, vaccine, and past COVID-19 disease. RESULTS: Antibodies nAb were detectable in 92.9% (95% CI: 89.7-96.0) of vaccinees. We observed statistically insignificant decrease of positive results from 93.9% (95% CI: 89.5-98.3) and 97.0% (95% CI: 92.8-100.0) in the first and second month after vaccination, respectively, to 91.7% (95% CI: 83.8-99.5) and 78.3% (95% CI: 61.4-95.1) in the third and fourth month, respectively. Quantitative results showed decreasing level of nAb in both genders, age groups and vaccines. Higher levels of nAb were found in younger age group and in COVID-19 convalescents. IgG Ab showed little dynamics in time. CONCLUSIONS: We found robust humoral response after vaccination with mRNA vaccines, however, decreasing nAb levels suggest that vaccine-induced humoral immunity is rapidly waning. This finding is relevant for adjustment of vaccination strategies with regard to inclusion of booster dose(s).


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/diagnosis , COVID-19/prevention & control , Czech Republic/epidemiology , Female , Humans , Immunoglobulin G , Male , Pandemics , Point-of-Care Testing , RNA, Messenger , SARS-CoV-2 , Vaccination
20.
Int J Mol Sci ; 23(14)2022 Jul 18.
Article in English | MEDLINE | ID: covidwho-1964011

ABSTRACT

Mycoplasma hyopneumoniae (Mhp), the primary pathogen causing Mycoplasma pneumonia of swine (MPS), brings massive economic losses worldwide. Genomic variability and post-translational protein modification can enhance the immune evasion of Mhp, which makes MPS prone to recurrent outbreaks on farms, even with vaccination or other treatments. The reverse vaccinology pipeline has been developed as an attractive potential method for vaccine development due to its high efficiency and applicability. In this study, a multi-epitope vaccine for Mhp was developed, and its immune responses were evaluated in mice and piglets. Genomic core proteins of Mhp were retrieved through pan-genome analysis, and four immunodominant antigens were screened by host homologous protein removal, membrane protein screening, and virulence factor identification. One immunodominant antigen, AAV27984.1 (membrane nuclease), was expressed by E. coli and named rMhp597. For epitope prioritization, 35 B-cell-derived epitopes were identified from the four immunodominant antigens, and 10 MHC-I and 6 MHC-II binding epitopes were further identified. The MHC-I/II binding epitopes were merged and combined to produce recombinant proteins MhpMEV and MhpMEVC6His, which were used for animal immunization and structural analysis, respectively. Immunization of mice and piglets demonstrated that MhpMEV could induce humoral and cellular immune responses. The mouse serum antibodies could detect all 11 synthetic epitopes, and the piglet antiserum suppressed the nuclease activity of rMhp597. Moreover, piglet serum antibodies could also detect cultured Mhp strain 168. In summary, this study provides immunoassay results for a multi-epitope vaccine derived from the reverse vaccinology pipeline, and offers an alternative vaccine for MPS.


Subject(s)
Mycoplasma hyopneumoniae , Pneumonia of Swine, Mycoplasmal , Animals , Bacterial Vaccines , Epitopes , Escherichia coli , Immunity, Cellular , Immunodominant Epitopes , Mycoplasma hyopneumoniae/genetics , Pneumonia of Swine, Mycoplasmal/prevention & control , Swine
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