Project description:BackgroundPublic health measures to stem the coronavirus disease 2019 (COVID-19) pandemic are challenged by social, economic, health status, and cultural disparities that facilitate disease transmission and amplify its severity. Prior pre-clinical biomedical technologic advances in nucleic acid-based vaccination enabled unprecedented speed of conceptualization, development, production, and widespread distribution of mRNA vaccines that target SARS-CoV-2's Spike (S) protein.DesignTwenty-five female and male volunteer fulltime employees at the Providence VA Medical Center participated in this study to examine longitudinal antibody responses to the Moderna mRNA-1273 vaccine. IgM-S and IgG-S were measured in serum using the Abbott IgM-S-Qualitative and IgG2-S-Quantitative chemiluminescent assays.ResultsPeak IgM responses after Vaccine Dose #1 were delayed in 6 (24%) and absent in 7 (28%) participants. IgG2-S peak responses primarily occurred 40 to 44 days after Vaccine Dose #1, which was also 11 to 14 days after Vaccine Dose #2. However, subgroups exhibited Strong (n = 6; 24%), Normal (n = 13; 52%), or Weak (n = 6; 24%) peak level responses that differed significantly from each other (P < .005 or better). The post-peak IgG2-S levels declined progressively, and within 6 months reached the mean level measured 1 month after Vaccine Dose #1. Weak responders exhibited persistently low levels of IgG2-S. Variability in vaccine responsiveness was unrelated to age or gender.ConclusionHost responses to SARS-CoV-2-Spike mRNA vaccines vary in magnitude, duration and occurrence. This study raises concern about the lack of vaccine protection in as many as 8% of otherwise normal people, and the need for open dialog about future re-boosting requirements to ensure long-lasting immunity via mRNA vaccination versus natural infection.
Project description:The optimal vaccination strategy to boost responses in the context of pre-existing immune memory to the SARS-CoV-2 spike (S) glycoprotein is an important question for global public health. To address this, we explored the SARS-CoV-2-specific humoral and cellular immune responses to a novel self-amplifying RNA (saRNA) vaccine followed by a UK authorised mRNA vaccine (BNT162b2) in individuals with and without previous COVID-19, and compared these responses with those who received an authorised vaccine alone. 35 subjects receiving saRNA (saRNA group) as part of the COVAC1 clinical trial and an additional 40 participants receiving an authorised SARS-CoV-2 vaccine only (non-saRNA group) were recruited. Antibody responses were measured by ELISA and a pseudoneutralisation assay for wildtype, Delta and Omicron variants. Cellular responses were measured by IFN-ƴ ELISpot and an activation induced marker (AIM) assay. Approximately 50% in each group had previous COVID-19 prior to vaccination, confirmed by PCR or antibody positivity on ELISA. All of those who received saRNA subsequently received a full course of an authorised vaccine. The majority (83%) of those receiving saRNA who were COVID-19 naïve at baseline seroconverted following the second dose, and those with previous COVID-19 had an increase in antibody titres two weeks following saRNA vaccination (median 27-fold), however titres were lower when compared to mRNA vaccination. Two weeks following the 2nd authorised mRNA vaccine dose, binding and neutralising antibody titres were significantly higher in the saRNA participants with previous COVID-19, compared to non-saRNA, or COVID-19 naive saRNA participants. Cellular responses were again highest in this group, with a higher proportion of spike specific CD8+ than CD4+ T cells when compared to those receiving the mRNA vaccine only. These findings suggest an immunological benefit of increased antigen exposure, both from natural infection and vaccination, particularly evident in those receiving heterologous vaccination with saRNA and mRNA.
Project description:IntroductionThe longitudinal responses towards multiple doses of COVID-19 mRNA vaccines in patients with systemic autoimmune diseases remain incompletely understood. While observational studies suggested the safety of COVID-19 mRNA vaccines in rheumatic disease patients, laboratory evidence is lacking.MethodsHere we evaluated seroreactivity, clinical manifestions, and multiple disease biomarkers after 2 or 3 doses of COVID-19 mRNA vaccines in a cohort of patients with rheumatic diseases.ResultsMost patients generated high SARS-CoV-2 spike-specific neutralizing antibodies comparable to those in healthy controls after 2 doses of mRNA vaccines. The antibody level declined over time but recovered after the third dose of the vaccine. Patients with systemic lupus erythematosus (SLE) or psoriatic arthritis (PsA) remained without significant flares post-vaccination. The changes in anti-dsDNA antibody concentration and expression of type I interferon (IFN) signature genes were highly variable but did not show consistent or significant increases. Frequency of double negative 2 (DN2) B cells remained largely stable.DiscussionOur data provide experimental evidences indicating the efficacy and safety of repeated COVID-19 mRNA vaccination in rheumatic disease patients.
Project description:Abstract Messenger RNA vaccines are the main COVID-19 vaccines authorized for use in the United States. Side effects are typically minor and transient. We report a case series of four subjects with an acute myocarditis-like illness following mRNA COVID-19 vaccination who were hospitalized at our hospital in Lubbock, Texas. Three patients were young men who presented with acute chest pain after the second dose of the mRNA-1273 vaccine. Another patient was a 53-year-old white woman who presented with acute left arm pain 3 days after the first dose of the mRNA-1273 vaccine. She was later found to have acute decompensated heart failure, and endomyocardial biopsy revealed eosinophilic injury–mediated myocarditis.
Project description:BackgroundClinical trials of the BNT162b2 vaccine, revealed efficacy and safety. We report six cases of myocarditis, which occurred shortly after BNT162b2 vaccination.MethodsPatients were identified upon presentation to the emergency department with symptoms of chest pain/discomfort. In all study patients, we excluded past and current COVID-19. Routine clinical and laboratory investigations for common etiologies of myocarditis were performed. Laboratory tests also included troponin and C-reactive protein levels. The diagnosis of myocarditis was established after cardiac MRI.FindingsFive patients presented after the second and one after the first dose of the vaccine. All patients were males with a median age of 23 years. Myocarditis was diagnosed in all patients, there was no evidence of COVID-19 infection. Laboratory assays excluded concomitant infection; autoimmune disorder was considered unlikely. All patients responded to the BNT162b2 vaccine. The clinical course was mild in all six patients.InterpretationOur report of myocarditis after BNT162b2 vaccination may be possibly considered as an adverse reaction following immunization. We believe our information should be interpreted with caution and further surveillance is warranted.
Project description:Although vaccines against COVID-19 are effective tools in preventing severe disease, recent studies have shown enhanced protection after vaccine boosters. The aim of our study was to examine the dynamics and duration of both humoral and cellular immune responses following a three-dose regimen of the BNT162b2 mRNA vaccine. In a longitudinal prospective study we enrolled 86 adults who received the BNT162b2 vaccine, 35 unvaccinated individuals with a history of mild COVID-19 and a control group of 30 healthy SARS-CoV-2 seronegative persons. We assessed the SARS-CoV-2-specific T cell responses and IgG production up to 12 months post the third BNT162b2 dose in 24 subjects. The vaccinated group had significantly higher IgG antibody levels after two doses compared to the convalescent group (p<0.001). After the third dose, IgG levels surged beyond those detected after the second dose (p<0.001). Notably, these elevated IgG levels were maintained 12 months post the third dose. After two doses, specific T cell responses were detected in 87.5% of the vaccinated group. Additionally, there was a significant decrease before the third dose. However, post the third dose, specific T cell responses surged and remained stable up to the 12-month period. Our findings indicate that the BNT162b2 vaccine induces potent and enduring humoral and cellular responses, which are notably enhanced by the third dose and remain persistant without a significant decline a year after the booster. Further research is essential to understand the potential need for subsequent boosters.
Project description:BackgroundAlthough there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets' analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses.MethodsIn this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed.ResultsThe white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells.ConclusionOur results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.
Project description:mRNA-based COVID-19 vaccines have played a critical role in reducing severe outcomes of COVID-19. Humoral immune responses against SARS-CoV-2 after vaccination have been extensively studied in blood; however, limited information is available on the presence and duration of SARS-CoV-2 specific antibodies in saliva and other mucosal fluids. Saliva offers a non-invasive sampling method that may also provide a better understanding of mucosal immunity at sites where the virus enters the body. Our objective was to evaluate the salivary immune response after vaccination with the COVID-19 Moderna mRNA-1273 vaccine. Two hundred three staff members of the U.S. Centers for Disease Control and Prevention were enrolled prior to receiving their first dose of the mRNA-1273 vaccine. Participants were asked to self-collect 6 saliva specimens at days 0 (prior to first dose), 14, 28 (prior to second dose), 42, and 56 using a SalivaBio saliva collection device. Saliva specimens were tested for anti-spike protein SARS-CoV-2 specific IgA and IgG enzyme immunoassays. Overall, SARS-CoV-2-specific salivary IgA titers peaked 2 weeks after each vaccine dose, followed by a sharp decrease during the following weeks. In contrast to IgA titers, IgG antibody titers increased substantially 2 weeks after the first vaccine dose, peaked 2 weeks after the second dose and persisted at an elevated level until at least 8 weeks after the first vaccine dose. Additionally, no significant differences in IgA/IgG titers were observed based on age, sex, or race/ethnicity. All participants mounted salivary IgA and IgG immune responses against SARS-CoV-2 after receiving the mRNA-1273 COVID-19 vaccine. Because of the limited follow-up time for this study, more data are needed to assess the antibody levels beyond 2 months after the first dose. Our results confirm the potential utility of saliva in assessing immune responses elicited by immunization and possibly by infection.