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Single-cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine.

ABSTRACT: mRNA vaccines for SARS-CoV-2 have shown exceptional clinical efficacy, providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used scRNA-Seq and functional assays to compare humoral and cellular responses to 2 doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4+ T cells, and robust antigen-specific polyfunctional CD4+ T cell responses following vaccination. On the other hand, although clonally expanded CD8+ T cells were observed following both vaccination and natural infection, CD8+ T cell responses were relatively weak and variable. In addition, TCR gene usage was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of CD8+ T cell clones that occupy distinct clusters compared to those induced by vaccination and likely recognize a broader set of viral antigens of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response in which early CD4+ T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8+ T cells, together capable of contributing to future recall responses.

SUBMITTER: Sureshchandra S

PROVIDER: S-EPMC8783687 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Severe autoimmune hemolytic anemia following receipt of SARS-CoV-2 mRNA vaccine.

Project description:BackgroundLarge clinical trials have demonstrated the overall safety of vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, reports have emerged of autoimmune phenomena, including vaccine-associated myocarditis, immune thrombocytopenia, and immune thrombotic thrombocytopenia.Case presentationHere we present a novel case of a young woman who developed life-threatening autoimmune hemolytic anemia (AIHA) after her first dose of a SARS-CoV-2 mRNA vaccine. Notably, initial direct antiglobulin testing was negative using standard anti-IgG reagents, which are "blind" to certain immunoglobulin (IgG) isotypes. Further testing using an antiglobulin reagent that detects all IgG isotypes was strongly positive and confirmed the diagnosis of AIHA. The patient required transfusion with 13 units of red blood cells, as well as treatment with corticosteroids, rituximab, mycophenolate mofetil, and immune globulin.ConclusionAs efforts to administer SARS-CoV-2 vaccines continue globally, clinicians must be aware of potential autoimmune sequelae of these therapies.

| S-EPMC8661722 | biostudies-literature

T-Cell Responses Induced by an Intradermal BNT162b2 mRNA Vaccine Booster Following Primary Vaccination with Inactivated SARS-CoV-2 Vaccine.

Project description:A practical booster vaccine is urgently needed to control the coronavirus disease (COVID-19) pandemic. We have previously reported the safety and immunogenicity of a fractional intradermal booster, using the BNT162b2 mRNA vaccine in healthy volunteers who had completed two doses of inactivated SARS-CoV-2 vaccine. In this study, an intramuscular booster at full dosage was used as a control, and a half-dose vaccination was included for reciprocal comparison. Detailed T-cell studies are essential to understand cellular responses to vaccination. T-cell immunity was examined using S1 peptide restimulation and flow cytometry. The fractional dose (1:5) of the BNT162b2 mRNA vaccine enhanced antigen-specific effector T-cells, but the responses were less remarkable compared to the intramuscular booster at full dosage. However, the intradermal regimen was not inferior to the intramuscular booster a month after boosting. An intradermal booster using only one-fifth of the standard dosage could provide comparable T-cell responses with the fractional intramuscular booster. This work confirms the efficacy of intradermal and fractional vaccination in terms of T-cell immunogenicity in previously immunised populations.

| S-EPMC9501140 | biostudies-literature

Antibody Responses after a Single Dose of SARS-CoV-2 mRNA Vaccine.

Project description: Not available

| S-EPMC8008753 | biostudies-literature

Case report: acute myocarditis following the second dose of mRNA-1273 SARS-CoV-2 vaccine

Project description:Abstract Background The SARS-CoV-2 pandemic has led to the development of the first mRNA vaccines used in humans. The vaccines are well tolerated, safe, and highly efficacious; however, post-marketing surveillance is revealing potential rare adverse effects. We report a case of symptomatic acute myocarditis following administration of the second dose of mRNA-1273 SARS-CoV-2 vaccine. Case summary A 44-year-old man presented with chest pain and ST-segment elevation 4 days after receiving the second dose of mRNA-1273 SARS-CoV-2 Vaccine. Emergent coronary angiogram showed minimal coronary artery disease. Cardiac magnetic resonance imaging confirmed acute myocarditis. Diagnosis of vaccine-associated myocarditis was made given the temporal relationship and supportive treatment initiated. Follow-up at 1 month confirmed complete symptomatic recovery and echocardiogram demonstrated normalization of cardiac function. Discussion Acute myocarditis should be considered in patients who present with chest pain or dyspnoea within days of receiving mRNA-1273 SARS-CoV-2 vaccination, especially after the second dose. This may be managed successfully with supportive therapies with complete recovery of cardiac function and symptoms. Further research is warranted to determine the mechanisms by which mRNA vaccines may cause myocarditis and for potential long-term cardiovascular injury.

| S-EPMC8422333 | biostudies-literature

Myopericarditis following SARS-CoV-2 mRNA vaccine: the role of cardiac biomarkers and multimodality imaging.

Project description: Not available

| S-EPMC8499913 | biostudies-literature

Symptomology following mRNA vaccination against SARS-CoV-2.

Project description:Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.

| S-EPMC8527734 | biostudies-literature

Antibody Responses in Seropositive Persons after a Single Dose of SARS-CoV-2 mRNA Vaccine.

Project description: Not available

| S-EPMC8008743 | biostudies-literature

An mRNA Vaccine against SARS-CoV-2 - Preliminary Report.

Project description:BackgroundThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally, prompting an international effort to accelerate development of a vaccine. The candidate vaccine mRNA-1273 encodes the stabilized prefusion SARS-CoV-2 spike protein.MethodsWe conducted a phase 1, dose-escalation, open-label trial including 45 healthy adults, 18 to 55 years of age, who received two vaccinations, 28 days apart, with mRNA-1273 in a dose of 25 μg, 100 μg, or 250 μg. There were 15 participants in each dose group.ResultsAfter the first vaccination, antibody responses were higher with higher dose (day 29 enzyme-linked immunosorbent assay anti-S-2P antibody geometric mean titer [GMT], 40,227 in the 25-μg group, 109,209 in the 100-μg group, and 213,526 in the 250-μg group). After the second vaccination, the titers increased (day 57 GMT, 299,751, 782,719, and 1,192,154, respectively). After the second vaccination, serum-neutralizing activity was detected by two methods in all participants evaluated, with values generally similar to those in the upper half of the distribution of a panel of control convalescent serum specimens. Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.ConclusionsThe mRNA-1273 vaccine induced anti-SARS-CoV-2 immune responses in all participants, and no trial-limiting safety concerns were identified. These findings support further development of this vaccine. (Funded by the National Institute of Allergy and Infectious Diseases and others; mRNA-1273 ClinicalTrials.gov number, NCT04283461).

| S-EPMC7377258 | biostudies-literature

Tracking B Cell Responses to the SARS-CoV-2 mRNA-1273 Vaccine

Project description:The COVID-19 pandemic left an unprecedented social and economic impact on the world. This rapidly evolving global instigated a worldwide effort to develop an effective vaccine. Despite the generation of a protective antibody response in most individuals after two doses of an anti-spike mRNA vaccine, some studies have shown that a poorer response is elicited in some individuals, particularly those that are immunocompromised or elderly. To gain further insight into the cellular mechanisms driving B cell evolution in response to vaccination against SARS-CoV-2, we performed longitudinal single-cell transcriptomic, epitope sequencing (CITE-seq), and repertoire profiling of three COVID-19 vaccinees. Spike-specific (S-2P+) B cells showed early immune activation at v1D14 (14 days after vaccine dose 1) and accumulation of somatic hyper mutation (SHM) up to v2M6 (months 6). At v2D6, the S-2P+ cells expanded into memory B cell (MBC) cluster 5 with a dynamic kinetics over time. At v2M6, majority of S-2P+ cells were into resting memory (RM) subset within cluster 5. Analysis of B cell receptor (BCR) repertoire showed selection of genes commonly detected in neutralizing monoclonal antibodies from COVID-19 patients. Tracking of S-2P+ B cell response showed clonal association between earlier activated CD38+ memory, as well as tissue-like memory, with RM B cells at v2M6. These clones showed evolving signal with progressive accumulation of SHM over time. The presence of early plasmablast (PB) within these clones corroborates our previous report that associates PB response with sustained immunity. This integrated analysis allowed us to characterize the transcriptional activity underpinning the development of B cells involved in inducing an immune response to the COVID-19 vaccine.

2023-07-07 | GSE219098 | GEO

Acute Myocarditis Following mRNA-1273 SARS-CoV-2 Vaccination.

Project description:Myocarditis has been described previously as a rare side effect of both influenza and smallpox vaccines. In this report, we present a case of acute perimyocarditis in a young, healthy man after vaccination with the mRNA-1273 severe acute respiratory syndrome coronavirus -2 (SARS-CoV-2; Moderna) vaccine. He presented with chest pain and decompensated heart failure 3 days after administration of his second dose, and his symptoms resolved by 9 days post-inoculation. This case highlights a rare but potentially serious side effect of this mRNA vaccine that primary care physicians and cardiologists should be aware of in order to identify and appropriately manage these patients.

| S-EPMC8278869 | biostudies-literature

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