Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 81
Filter
Add filters

Document Type
Year range
1.
Neurol Neuroimmunol Neuroinflamm ; 9(1)2022 01.
Article in English | MEDLINE | ID: covidwho-1591928

ABSTRACT

BACKGROUND AND OBJECTIVES: There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS. METHODS: Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity. RESULTS: In 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction. DISCUSSION: SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , COVID-19/complications , COVID-19/immunology , Immunogenicity, Vaccine/immunology , Multiple Sclerosis/complications , Multiple Sclerosis/immunology , Adult , Aged , COVID-19/prevention & control , COVID-19/virology , Cross-Sectional Studies , Female , Humans , Immunization, Secondary/adverse effects , Internet , Male , Middle Aged , Multiple Sclerosis/virology , Retrospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Surveys and Questionnaires , Vaccination/adverse effects , Vaccination/statistics & numerical data
2.
Front Immunol ; 12: 765211, 2021.
Article in English | MEDLINE | ID: covidwho-1581337

ABSTRACT

Saturation suppressor mutagenesis was used to generate thermostable mutants of the SARS-CoV-2 spike receptor-binding domain (RBD). A triple mutant with an increase in thermal melting temperature of ~7°C with respect to the wild-type B.1 RBD and was expressed in high yield in both mammalian cells and the microbial host, Pichia pastoris, was downselected for immunogenicity studies. An additional derivative with three additional mutations from the B.1.351 (beta) isolate was also introduced into this background. Lyophilized proteins were resistant to high-temperature exposure and could be stored for over a month at 37°C. In mice and hamsters, squalene-in-water emulsion (SWE) adjuvanted formulations of the B.1-stabilized RBD were considerably more immunogenic than RBD lacking the stabilizing mutations and elicited antibodies that neutralized all four current variants of concern with similar neutralization titers. However, sera from mice immunized with the stabilized B.1.351 derivative showed significantly decreased neutralization titers exclusively against the B.1.617.2 (delta) VOC. A cocktail comprising stabilized B.1 and B.1.351 RBDs elicited antibodies with qualitatively improved neutralization titers and breadth relative to those immunized solely with either immunogen. Immunized hamsters were protected from high-dose viral challenge. Such vaccine formulations can be rapidly and cheaply produced, lack extraneous tags or additional components, and can be stored at room temperature. They are a useful modality to combat COVID-19, especially in remote and low-resource settings.


Subject(s)
Antibodies, Neutralizing/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Viral/immunology , Cricetinae , Immunogenicity, Vaccine/immunology , Mice , Spike Glycoprotein, Coronavirus/genetics
3.
Front Immunol ; 12: 766112, 2021.
Article in English | MEDLINE | ID: covidwho-1581336

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern. The development of vaccines with high immunogenicity and safety is crucial for controlling the global COVID-19 pandemic and preventing further illness and fatalities. Here, we report the development of a SARS-CoV-2 vaccine candidate, Nanocovax, based on recombinant protein production of the extracellular (soluble) portion of the spike (S) protein of SARS-CoV-2. The results showed that Nanocovax induced high levels of S protein-specific IgG and neutralizing antibodies in three animal models: BALB/c mouse, Syrian hamster, and a non-human primate (Macaca leonina). In addition, a viral challenge study using the hamster model showed that Nanocovax protected the upper respiratory tract from SARS-CoV-2 infection. Nanocovax did not induce any adverse effects in mice (Mus musculus var. albino) and rats (Rattus norvegicus). These preclinical results indicate that Nanocovax is safe and effective.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/toxicity , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , Spike Glycoprotein, Coronavirus/immunology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Cricetinae , Macaca , Mice , Rats , SARS-CoV-2 , Vaccines, Synthetic/immunology , Vaccines, Synthetic/toxicity
4.
Front Immunol ; 12: 803742, 2021.
Article in English | MEDLINE | ID: covidwho-1581314

ABSTRACT

Immunocompromised patients are considered high-risk and prioritized for vaccination against COVID-19. We aimed to analyze B-cell subsets in these patients to identify potential predictors of humoral vaccination response. Patients (n=120) suffering from hematologic malignancies or other causes of immunodeficiency and healthy controls (n=79) received a full vaccination series with an mRNA vaccine. B-cell subsets were analyzed prior to vaccination. Two independent anti-SARS-CoV-2 immunoassays targeting the receptor-binding domain (RBD) or trimeric S protein (TSP) were performed three to four weeks after the second vaccination. Seroconversion occurred in 100% of healthy controls, in contrast to 67% (RBD) and 82% (TSP) of immunocompromised patients, while only 32% (RBD) and 22% (TSP) achieved antibody levels comparable to those of healthy controls. The number of circulating CD19+IgD+CD27- naïve B cells was strongly associated with antibody levels (ρ=0.761, P<0.001) and the only independent predictor for achieving antibody levels comparable to healthy controls (OR 1.07 per 10-µL increase, 95%CI 1.02-1.12, P=0.009). Receiver operating characteristic analysis identified a cut-off at ≥61 naïve B cells per µl to discriminate between patients with and without an optimal antibody response. Consequently, measuring of naïve B cells in immunocompromised hematologic patients could be useful in predicting their humoral vaccination response.


Subject(s)
B-Lymphocyte Subsets/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host/immunology , Immunogenicity, Vaccine/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Female , Humans , Male , Middle Aged , SARS-CoV-2 , Vaccines, Synthetic/immunology , /immunology
5.
Eur J Cancer ; 157: 441-449, 2021 11.
Article in English | MEDLINE | ID: covidwho-1573973

ABSTRACT

INTRODUCTION: Patients with cancer are presumed a frail group at high risk of contracting coronavirus disease (COVID-19), and vaccination represents a cornerstone in addressing the COVID-19 pandemic. However, data on COVID-19 vaccination in cancer patients are fragmentary and poor. METHODS: An observational study was conducted to evaluate the seropositivity rate and safety of a two-dose regimen of the BNT162b2 or messenger RNA-1273 vaccine in adult patients with solid cancer undergoing active anticancer treatment or whose treatment had been terminated within 6 months of the start of the study. The control group was composed of healthy volunteers. Serum samples were evaluated for SARS-COV-2 antibodies before vaccinations and 2-6 weeks after the administration of the second vaccine dose. Primary end-point: seropositivity rate. Secondary end-points: safety, factors influencing seroconversion, IgG titers of patients versus healthy volunteers, COVID-19 infection. RESULTS: Between 20th March 2021 and 12th June 2021, 293 consecutive patients with cancer-solid tumours underwent a program of COVID-19 vaccinations; of these, 2 patients refused vaccination, 13 patients did not receive the second dose of the vaccine because of cancer progression, and 21 patients had COVID-19 antibodies at baseline and were excluded. The 257 evaluable patients had a median age of 65 years (range 28-86), 66.15% with metastatic disease. Primary end-point: seropositivity rate in patients was 75.88% versus 100% in the control group. Secondary end-points: no Grade 3-4 side-effects, no COVID-19 infections were reported. Patients median IgG titer was significantly lower than in the control group; male sex and active anticancer therapy influenced negative seroconversion. BNT162b2 or messenger RNA-1273 vaccines were immunogenic in cancer patients, showing good safety profile.


Subject(s)
COVID-19 Vaccines/immunology , Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/immunology , Female , Humans , Immunogenicity, Vaccine/immunology , Italy , Male , Middle Aged , Neoplasms/virology , Pandemics/prevention & control , Prospective Studies , SARS-CoV-2/immunology , Vaccination/methods
6.
Int Immunol ; 33(10): 529-540, 2021 09 25.
Article in English | MEDLINE | ID: covidwho-1575943

ABSTRACT

Coronavirus disease 2019 (COVID-19) has caused millions of deaths, and serious consequences to public health, economies and societies. Rapid responses in vaccine development have taken place since the isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the release of the viral genome sequence. By 21 May 2021, 101 vaccines were under clinical trials, and published data were available for 18 of them. Clinical study results from some vaccines indicated good immunogenicity and acceptable reactogenicity. Here, we focus on these 18 vaccines that had published clinical data to dissect the induced humoral and cellular immune responses as well as their safety profiles and protection efficacy.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Animals , Humans , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology
7.
J Med Virol ; 94(1): 88-98, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544348

ABSTRACT

The outbreak of the current coronavirus disease (COVID-19) occurred in late 2019 and quickly spread all over the world. The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) belongs to a genetically diverse group that mutates continuously leading to the emergence of multiple variants. Although a few antiviral agents and anti-inflammatory medicines are available, thousands of individuals have passed away due to emergence of new viral variants. Thus, proper surveillance of the SARS-CoV-2 genome is needed for the rapid identification of developing mutations over time, which are of the major concern if they occur specifically in the surface spike proteins of the virus (neutralizing analyte). This article reviews the potential mutations acquired by the SARS-CoV2 since the pandemic began and their significant impact on the neutralizing efficiency of vaccines and validity of the diagnostic assays.


Subject(s)
COVID-19/epidemiology , Genetic Drift , Genome, Viral/genetics , RNA, Viral/genetics , SARS-CoV-2/genetics , Antibodies, Neutralizing/immunology , Gene Frequency/genetics , Genetic Variation/genetics , Humans , Immunogenicity, Vaccine/immunology , Spike Glycoprotein, Coronavirus/genetics
8.
J Med Virol ; 94(1): 407-412, 2022 01.
Article in English | MEDLINE | ID: covidwho-1544345

ABSTRACT

The ChAdOx1 nCoV-19 vaccine (Oxford University-Astra Zeneca) has demonstrated nearly 70% efficacy against symptomatic COVID-19 in trials and some real-world studies. The vaccine was the first to be approved in India in early January 2021 and is manufactured by the Serum Institute of India. Favorable short-term safety data of the vaccine in India in a real-world setting has been recently demonstrated. Here, we report secondary objective (COVID-19 occurrence) measures of the same ongoing prospective observational study in prioritized recipients of the vaccine. The findings are based on participants who could complete at least 2 months of follow-up (n = 1500; female/male: 472/1028; mean age: 38.8 years). Laboratory confirmed SARS-CoV-2 infection was observed in 27/65 participants (41%) who received a single dose and 271/1435 (19%) who received both doses. Specifically, among doctors, 18/27 (66.7%) one dose recipients and 131/377 (34.7%) fully vaccinated developed SARS-CoV-2 infection. The majority of the cases were mild in all groups, and most were breakthrough infections. The occurrence of "severe" COVID-19 was 7.7 times lower (0.4%) in fully vaccinated participants compared to partially vaccinated (3.1%). Four deaths were observed in the study. One of the four deaths was due to sepsis, two due to unspecified cardiac events, and one due to unspecified post-COVID-19 complications. The results of this preliminary analysis necessitate vigorous research on the performance of vaccines against variants, optimal timing of vaccination, and also optimal timings of effectiveness studies to guide future vaccination policy.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , Adult , COVID-19/epidemiology , COVID-19/mortality , Comorbidity , Female , Humans , Immunization, Secondary/statistics & numerical data , India/epidemiology , Male , Prospective Studies , Severity of Illness Index , Vaccination
9.
Lancet Oncol ; 22(6): 765-778, 2021 06.
Article in English | MEDLINE | ID: covidwho-1531901

ABSTRACT

BACKGROUND: The efficacy and safety profiles of vaccines against SARS-CoV-2 in patients with cancer is unknown. We aimed to assess the safety and immunogenicity of the BNT162b2 (Pfizer-BioNTech) vaccine in patients with cancer. METHODS: For this prospective observational study, we recruited patients with cancer and healthy controls (mostly health-care workers) from three London hospitals between Dec 8, 2020, and Feb 18, 2021. Participants who were vaccinated between Dec 8 and Dec 29, 2020, received two 30 µg doses of BNT162b2 administered intramuscularly 21 days apart; patients vaccinated after this date received only one 30 µg dose with a planned follow-up boost at 12 weeks. Blood samples were taken before vaccination and at 3 weeks and 5 weeks after the first vaccination. Where possible, serial nasopharyngeal real-time RT-PCR (rRT-PCR) swab tests were done every 10 days or in cases of symptomatic COVID-19. The coprimary endpoints were seroconversion to SARS-CoV-2 spike (S) protein in patients with cancer following the first vaccination with the BNT162b2 vaccine and the effect of vaccine boosting after 21 days on seroconversion. All participants with available data were included in the safety and immunogenicity analyses. Ongoing follow-up is underway for further blood sampling after the delayed (12-week) vaccine boost. This study is registered with the NHS Health Research Authority and Health and Care Research Wales (REC ID 20/HRA/2031). FINDINGS: 151 patients with cancer (95 patients with solid cancer and 56 patients with haematological cancer) and 54 healthy controls were enrolled. For this interim data analysis of the safety and immunogenicity of vaccinated patients with cancer, samples and data obtained up to March 19, 2021, were analysed. After exclusion of 17 patients who had been exposed to SARS-CoV-2 (detected by either antibody seroconversion or a positive rRT-PCR COVID-19 swab test) from the immunogenicity analysis, the proportion of positive anti-S IgG titres at approximately 21 days following a single vaccine inoculum across the three cohorts were 32 (94%; 95% CI 81-98) of 34 healthy controls; 21 (38%; 26-51) of 56 patients with solid cancer, and eight (18%; 10-32) of 44 patients with haematological cancer. 16 healthy controls, 25 patients with solid cancer, and six patients with haematological cancer received a second dose on day 21. Of the patients with available blood samples 2 weeks following a 21-day vaccine boost, and excluding 17 participants with evidence of previous natural SARS-CoV-2 exposure, 18 (95%; 95% CI 75-99) of 19 patients with solid cancer, 12 (100%; 76-100) of 12 healthy controls, and three (60%; 23-88) of five patients with haematological cancers were seropositive, compared with ten (30%; 17-47) of 33, 18 (86%; 65-95) of 21, and four (11%; 4-25) of 36, respectively, who did not receive a boost. The vaccine was well tolerated; no toxicities were reported in 75 (54%) of 140 patients with cancer following the first dose of BNT162b2, and in 22 (71%) of 31 patients with cancer following the second dose. Similarly, no toxicities were reported in 15 (38%) of 40 healthy controls after the first dose and in five (31%) of 16 after the second dose. Injection-site pain within 7 days following the first dose was the most commonly reported local reaction (23 [35%] of 65 patients with cancer; 12 [48%] of 25 healthy controls). No vaccine-related deaths were reported. INTERPRETATION: In patients with cancer, one dose of the BNT162b2 vaccine yields poor efficacy. Immunogenicity increased significantly in patients with solid cancer within 2 weeks of a vaccine boost at day 21 after the first dose. These data support prioritisation of patients with cancer for an early (day 21) second dose of the BNT162b2 vaccine. FUNDING: King's College London, Cancer Research UK, Wellcome Trust, Rosetrees Trust, and Francis Crick Institute.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/immunology , Neoplasms/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , COVID-19/blood , COVID-19/complications , COVID-19/virology , COVID-19 Vaccines/immunology , Dose-Response Relationship, Immunologic , Female , Humans , Immunogenicity, Vaccine/immunology , London/epidemiology , Male , Middle Aged , Neoplasms/blood , Neoplasms/complications , Neoplasms/virology , Prospective Studies , SARS-CoV-2 , Wales
10.
J Immunother Cancer ; 9(10)2021 10.
Article in English | MEDLINE | ID: covidwho-1495513

ABSTRACT

Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B cell malignancies have profound and prolonged immunodeficiencies and are at risk for serious infections, including respiratory virus infections. Vaccination may be important for infection prevention, but there are limited data on vaccine immunogenicity in this population. We conducted a prospective observational study of the humoral immunogenicity of commercially available 2019-2020 inactivated influenza vaccines in adults immediately prior to or while in durable remission after CD19-, CD20-, or B cell maturation antigen-targeted CAR-T-cell therapy, as well as controls. We tested for antibodies to all four vaccine strains using neutralization and hemagglutination inhibition (HAI) assays. Antibody responses were defined as at least fourfold titer increases from baseline. Seroprotection was defined as a HAI titer ≥40. Enrolled CAR-T-cell recipients were vaccinated 14-29 days prior to (n=5) or 13-57 months following therapy (n=13), and the majority had hypogammaglobulinemia and cellular immunodeficiencies prevaccination. Eight non-immunocompromised adults served as controls. Antibody responses to ≥1 vaccine strain occurred in 2 (40%) individuals before CAR-T-cell therapy and in 4 (31%) individuals vaccinated after CAR-T-cell therapy. An additional 1 (20%) and 6 (46%) individuals had at least twofold increases, respectively. One individual vaccinated prior to CAR-T-cell therapy maintained a response for >3 months following therapy. Across all tested vaccine strains, seroprotection was less frequent in CAR-T-cell recipients than in controls. There was evidence of immunogenicity even among individuals with low immunoglobulin, CD19+ B cell, and CD4+ T-cell counts. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B cell aplasia. However, relatively impaired humoral vaccine immunogenicity indicates the need for additional infection-prevention strategies. Larger studies are needed to refine our understanding of potential correlates of vaccine immunogenicity, and durability of immune responses, in CAR-T-cell therapy recipients.


Subject(s)
Cell- and Tissue-Based Therapy/methods , Hemagglutination Inhibition Tests/methods , Immunogenicity, Vaccine/immunology , Influenza, Human/drug therapy , Influenza, Human/immunology , Adolescent , Adult , Aged , Humans , Middle Aged , Prospective Studies , Young Adult
11.
JAMA Netw Open ; 4(10): e2131749, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1490644

ABSTRACT

Importance: Adults receiving dialysis treatment have a higher likelihood of death when infected with SARS-CoV-2 than adults not receiving dialysis treatment. To date, the immune response of people receiving dialysis after SARS-CoV-2 vaccination has not been systematically discussed. Objective: To assess immunogenicity rates in people with end-stage kidney disease (ESKD) receiving SARS-CoV-2 vaccines, explore postvaccination potential risk factors for nonresponse, and assess whether receiving dialysis is associated with different antibody response rates compared with the nondialysis population. Data Sources: This systematic review and meta-analysis used articles from PubMed, Medline, and Embase published before July 30, 2021, as well as articles in the medRxiv preprint server. Study Selection: Studies that evaluated the immunogenicity rate according to the postvaccine antibody response rate in patients with ESKD receiving dialysis were selected. Data Extraction and Synthesis: The meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. A random-effects model was used. Two independent reviewers conducted the literature search and extracted the data. Main Outcomes and Measures: The primary outcome was the pooled antibody postvaccine response rates in individuals with ESKD. The secondary outcomes were pooled response rates in individuals receiving and not receiving dialysis. Subgroup analysis and meta-regression were conducted to identify the sources of heterogeneity. Results: A total of 32 studies were included. The overall immunogenicity rate of the dialysis group was 86% (95% CI, 81%-89%). Meta-regression showed a significant difference was detected in the postvaccine response rate on the basis of prevalence of diabetes (regression coefficient, -0.06; 95% CI, -0.10 to -0.02; P = .004). Compared with nondialysis controls, patients in the dialysis group had a lower response rate after the first (relative risk [RR], 0.61; 95% CI, 0.47-0.79; I2 = 70.2%) and second (RR, 0.88; 95% CI, 0.82-0.93; I2 = 72.2%) doses, with statistically significantly increased RR between first and second doses (P = .007). Conclusions and Relevance: These findings suggest that the immunogenicity rate among patients receiving dialysis was 41% after the first dose and 89% after the second dose. Diabetes might be a risk factor for nonresponse in the dialysis population. Patients receiving dialysis had a poorer antibody response rate than did individuals not receiving dialysis, particularly after the first dose.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunogenicity, Vaccine/immunology , Kidney Failure, Chronic/therapy , COVID-19/epidemiology , COVID-19/immunology , Diabetes Mellitus/epidemiology , Humans , Pandemics , Renal Dialysis/adverse effects , Renal Dialysis/statistics & numerical data , SARS-CoV-2 , Vaccination/statistics & numerical data
12.
Front Immunol ; 12: 727850, 2021.
Article in English | MEDLINE | ID: covidwho-1477821

ABSTRACT

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.


Subject(s)
Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine/immunology , Primary Immunodeficiency Diseases/immunology , SARS-CoV-2/immunology , Adolescent , Adult , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD4 Lymphocyte Count , COVID-19/prevention & control , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunocompromised Host/immunology , Longitudinal Studies , Male , Middle Aged , Vaccination , Young Adult
13.
Front Immunol ; 12: 726960, 2021.
Article in English | MEDLINE | ID: covidwho-1477820

ABSTRACT

Objectives: In the context of the Covid-19 pandemic, the fast development of vaccines with efficacy of around 95% preventing Covid-19 illness provides a unique opportunity to reduce the mortality associated with the pandemic. However, in the absence of efficacious prophylactic medications and few treatments for this infection, the induction of a fast and robust protective immunity is required for effective disease control, not only to prevent the disease but also the infection and shedding/transmission. The objective of our study was to analyze the level of specific humoral and cellular T-cell responses against the spike protein of SARS-CoV-2 induced by two mRNA-based vaccines (BNT162b2 and mRNA-1273), but also how long it takes after vaccination to induce these protective humoral and cellular immune responses. Methods: We studied in 40 healthy (not previously infected) volunteers vaccinated with BNT162b2 or mRNA-1273 vaccines the presence of spike-specific IgG antibodies and SARS-CoV-2-specific T cells at 3, 7 and 14 days after receiving the second dose of the vaccine. The specific T-cell response was analyzed stimulating fresh whole blood from vaccinated volunteers with SARS-CoV-2 peptides and measuring the release of cytokines secreted by T cells in response to SARS-CoV-2 stimulation. Results: Our results indicate that the immunization capacity of both vaccines is comparable. However, although both BNT162b2 and mRNA-1273 vaccines can induce early B-cell and T-cell responses, these vaccine-mediated immune responses do not reach their maximum values until 14 days after completing the vaccination schedule. Conclusion: This refractory period in the induction of specific immunity observed after completing the vaccination could constitute a window of higher infection risk, which could explain some emerging cases of SARS-CoV-2 infection in vaccinated people.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines/immunology , Immunogenicity, Vaccine/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Adult , Antibodies, Neutralizing/immunology , COVID-19/prevention & control , Female , Humans , Immunity, Cellular/immunology , Immunity, Humoral/immunology , Immunization Schedule , Immunoglobulin G/blood , Lymphocyte Count , Male , Prospective Studies , Vaccination
15.
Front Immunol ; 12: 742914, 2021.
Article in English | MEDLINE | ID: covidwho-1472387

ABSTRACT

Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/immunology , COVID-19/immunology , SARS-CoV-2/immunology , T-Lymphocytes/immunology , Vaccines, Inactivated/immunology , Adult , Aged , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/pathology , Chile , Comorbidity , Female , Humans , Immunization Schedule , Immunogenicity, Vaccine/immunology , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interferon-gamma/immunology , Lymphocyte Count , Male , Middle Aged , Severity of Illness Index , Vaccination , Young Adult
16.
Ann Rheum Dis ; 80(10): 1255-1265, 2021 10.
Article in English | MEDLINE | ID: covidwho-1467676

ABSTRACT

Patients with rheumatic diseases are at increased risk of infectious complications; vaccinations are a critical component of their care. Disease-modifying antirheumatic drugs may reduce the immunogenicity of common vaccines. We will review here available data regarding the effect of these medications on influenza, pneumococcal, herpes zoster, SARS-CoV-2, hepatitis B, human papilloma virus and yellow fever vaccines. Rituximab has the most substantial impact on vaccine immunogenicity, which is most profound when vaccinations are given at shorter intervals after rituximab dosing. Methotrexate has less substantial effect but appears to adversely impact most vaccine immunogenicity. Abatacept likely decrease vaccine immunogenicity, although these studies are limited by the lack of adequate control groups. Janus kinase and tumour necrosis factor inhibitors decrease absolute antibody titres for many vaccines, but do not seem to significantly impact the proportions of patients achieving seroprotection. Other biologics (interleukin-6R (IL-6R), IL-12/IL-23 and IL-17 inhibitors) have little observed impact on vaccine immunogenicity. Data regarding the effect of these medications on the SARS-CoV-2 vaccine immunogenicity are just now emerging, and early glimpses appear similar to our experience with other vaccines. In this review, we summarise the most recent data regarding vaccine response and efficacy in this setting, particularly in light of current vaccination recommendations for immunocompromised patients.


Subject(s)
Antirheumatic Agents/therapeutic use , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Immunocompromised Host , Immunogenicity, Vaccine/immunology , Rheumatic Diseases/drug therapy , COVID-19/complications , COVID-19 Vaccines/therapeutic use , Humans , Rheumatic Diseases/complications , SARS-CoV-2
17.
J Hepatol ; 75(2): 439-441, 2021 08.
Article in English | MEDLINE | ID: covidwho-1454288

ABSTRACT

BACKGROUND & AIMS: The development of COVID-19 vaccines has progressed with encouraging safety and efficacy data. Concerns have been raised about SARS-CoV-2 vaccine responses in the large population of patients with non-alcoholic fatty liver disease (NAFLD). The study aimed to explore the safety and immunogenicity of COVID-19 vaccination in NAFLD. METHODS: This multicenter study included patients with NAFLD without a history of SARS-CoV-2 infection. All patients were vaccinated with 2 doses of inactivated vaccine against SARS-CoV-2. The primary safety outcome was the incidence of adverse reactions within 7 days after each injection and overall incidence of adverse reactions within 28 days, and the primary immunogenicity outcome was neutralizing antibody response at least 14 days after the whole-course vaccination. RESULTS: A total of 381 patients with pre-existing NAFLD were included from 11 designated centers in China. The median age was 39.0 years (IQR 33.0-48.0 years) and 179 (47.0%) were male. The median BMI was 26.1 kg/m2 (IQR 23.8-28.1 kg/m2). The number of adverse reactions within 7 days after each injection and adverse reactions within 28 days totaled 95 (24.9%) and 112 (29.4%), respectively. The most common adverse reactions were injection site pain in 70 (18.4%), followed by muscle pain in 21 (5.5%), and headache in 20 (5.2%). All adverse reactions were mild and self-limiting, and no grade 3 adverse reactions were recorded. Notably, neutralizing antibodies against SARS-CoV-2 were detected in 364 (95.5%) patients with NAFLD. The median neutralizing antibody titer was 32 (IQR 8-64), and the neutralizing antibody titers were maintained. CONCLUSIONS: The inactivated COVID-19 vaccine appears to be safe with good immunogenicity in patients with NAFLD. LAY SUMMARY: The development of vaccines against coronavirus disease 2019 (COVID-19) has progressed rapidly, with encouraging safety and efficacy data. This study now shows that the inactivated COVID-19 vaccine appears to be safe with good immunogenicity in the large population of patients with non-alcoholic fatty liver disease.


Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 , Immunogenicity, Vaccine/immunology , Non-alcoholic Fatty Liver Disease , Vaccination , Vaccines, Inactivated , Adult , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , China/epidemiology , Female , Humans , Male , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/epidemiology , Outcome Assessment, Health Care , SARS-CoV-2/immunology , Vaccination/adverse effects , Vaccination/methods , Vaccination/statistics & numerical data , Vaccines, Inactivated/administration & dosage , Vaccines, Inactivated/adverse effects
18.
J Hepatol ; 75(2): 435-438, 2021 08.
Article in English | MEDLINE | ID: covidwho-1454287

ABSTRACT

BACKGROUND & AIMS: Two SARS-CoV-2 mRNA vaccines were approved to prevent COVID-19 infection, with reported vaccine efficacy of 95%. Liver transplant (LT) recipients are at risk of lower vaccine immunogenicity and were not included in the registration trials. We assessed vaccine immunogenicity and safety in this special population. METHODS: LT recipients followed at the Tel-Aviv Sourasky Medical Center and healthy volunteers were tested for SARS-CoV-2 IgG antibodies directed against the Spike-protein (S) and Nucleocapsid-protein (N) 10-20 days after receiving the second Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine dose. Information regarding vaccine side effects and clinical data was collected from patients and medical records. RESULTS: Eighty LT recipients were enrolled. Mean age was 60 years and 30% were female. Twenty-five healthy volunteer controls were younger (mean age 52.7 years, p = 0.013) and mostly female (68%, p = 0.002). All participants were negative for IgG N-protein serology, indicating immunity did not result from prior COVID-19 infection. All controls were positive for IgG S-protein serology. Immunogenicity among LT recipients was significantly lower with positive serology in only 47.5% (p <0.001). Antibody titer was also significantly lower in this group (mean 95.41 AU/ml vs. 200.5 AU/ml in controls, p <0.001). Predictors for negative response among LT recipients were older age, lower estimated glomerular filtration rate, and treatment with high dose steroids and mycophenolate mofetil. No serious adverse events were reported in either group. CONCLUSION: LT recipients developed substantially lower immunological response to the Pfizer-BioNTech SARS-CoV-2 mRNA-based vaccine. Factors influencing serological antibody responses include age, renal function and immunosuppressive medications. The findings require re-evaluation of vaccine regimens in this population. LAY SUMMARY: The Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine elicited substantially inferior immunity in liver transplant recipients. Less than half of the patients developed sufficient levels of antibodies against the virus, and in those who were positive, average antibody levels were 2x less compared to healthy controls. Factors predicting non-response were older age, renal function and immunosuppressive medications.


Subject(s)
Antibodies, Viral/blood , COVID-19 Vaccines , COVID-19 , Immunogenicity, Vaccine/immunology , Immunoglobulin G/blood , Immunosuppressive Agents/therapeutic use , Liver Transplantation/methods , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Female , Humans , Israel/epidemiology , Kidney Function Tests , Male , Middle Aged , Risk Factors , SARS-CoV-2/immunology , Serologic Tests/methods , Serologic Tests/statistics & numerical data , Vaccination/adverse effects , Vaccination/methods
19.
Front Immunol ; 12: 737406, 2021.
Article in English | MEDLINE | ID: covidwho-1450813

ABSTRACT

IL-7/IL-7R signaling is critical for development, maturation, maintenance and survival of many lymphocytes in the thymus and periphery. IL-7 has been used as immunotherapy in pre-clinical and clinical studies to treat cancer, HIV infection and sepsis. Here, we discuss the critical function of IL-7 in diagnosis, prognosis and treatment of COVID-19 patients. We also summarize a promising role of IL-7 as a vaccine adjuvant. It could potentially enhance the immune responses to vaccines especially against SARS-CoV-2 or other new vaccines.


Subject(s)
Adjuvants, Immunologic , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Interleukin-7/immunology , SARS-CoV-2/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Humans , Immunogenicity, Vaccine/immunology , Interleukin-7/metabolism , Receptors, Interleukin-7/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...