mRNA-1273 Vaccine Research Articles

Retinal Artery and Vein Occlusion Risks after Coronavirus Disease 2019 or Coronavirus Disease 2019 Vaccination

To evaluate the incidence of new retinal artery occlusion (RAO) and retinal vein occlusion (RVO) after the diagnosis of coronavirus disease 2019 (COVID-19) or vaccination against COVID-19 and compare the incidences with the population with neither. Nationwide population-based cohort study. From a nationwide population-based cohort, 8 418 590 patients were categorized into control (group 1), COVID-19 infection (group 2), and COVID-19 vaccination (group 3) groups. The cumulative incidence of RAO and RVO was calculated in groups 1, 2, and 3 using the Kaplan-Meier method. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) based on the Poisson distribution for RAO and RVO according to each group and subgroup using Cox proportional hazards models, with group 1 as the reference. We conducted univariable and multivariable analyses for the risk factors of RAO and RVO according to each subgroup. Cumulative incidence and risks of incidence of RAO and RVO from the index date to day60. In multivariable analysis, no significant increase in RAO and RVO risks after COVID-19 or COVID-19 vaccination were observed in either men or women. These results were observed consistently across various conditions in sensitivity analyses. In subgroup analysis, individuals who were vaccinated before infection showed no significant increase in RAO or RVO risks in both sexes compared with the control group. In the subgroup analysis of vaccinated patients, the HRs of RAO and RVO for different vaccine types did not show an increase compared with the control group; however, an exception was observed in women who received mRNA-1273 vaccines, who showed a higher RAO HR (4.65; 95% CI, 1.27-17.03; P= 0.021). Within 60 days of COVID-19 diagnosis or vaccination, RAO and RVO occurred rarely. We observed no increase in the HR of RVO and RAO relative to COVID-19 or COVID-19 vaccination except for a possible increase in the RAO HR in women who received mRNA-1273, for which the raw incidence was extremely low. Further investigation is required to validate this result. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Monitoring strategy of COVID-19 vaccination in dialysis patients based on a multiplex immunodot method: The CovidDial study.

COVID-19 vaccine was demonstrated to be effective in dialysis patients, but boosters are mandatory due to a rapid waning of anti-spike antibodies. A vaccination strategy based on immunologic response might be useful to maintain a favorable risk-benefit balance in this vulnerable population. CoviDial is an observational prospective study enrolling 121 dialysis patients to receive a 3-dose mRNA-1273 vaccine according to a uniform schedule. At baseline, months 1, 3, 6, 9, and 12, anti-spike antibodies against four epitopes (S1, S2, ECD-S1 + S2, RBD) were monitored with a multiplex immunodot enzymatic assay. Potential correlation between initial serologic response and subsequent COVID-19 infection was then assessed. Overall, 96.2% and 96.8% of patients had anti-RBD antibodies at 3 and 12 months, respectively. All antibodies titers significantly decreased at month 6 compared to month 3. Booster vaccine induced a robust serologic response at month 9, but with a waning 3 months later, particularly for anti-S2 (37.2±3.3 vs. 61.3±3.0, p< 0.0001) and anti-S1 + S2 antibodies (68.4±3.3 vs. 88.4±2.3, p= 0.0015). Fifteen patients were later tested positive for SARS-CoV-2. At month 3, mean titers of anti-RBD, anti-S1 + S2, and anti-S2 antibodies were lower in the subsequent SARS-CoV-2 infected cohort (71.57 ±9.01 vs. 85.79 ±2.61, p= 0.0131; 41.07 ±7.96 vs. 61.68 ±3.56, p= 0.0237; 13.79 ±5.03 vs. 39.70 ±3.86, p= 0.0096; respectively). Three doses of mRNA-1273 vaccine induce a robust but time-limited immunologic response in dialysis patients. Lower anti-spike antibodies titers after initial vaccination are associated with a higher risk to subsequently contract SARS-CoV-2, even beyond 6 months.

Comparative effectiveness of mRNA-1273 and BNT162b2 COVID-19 vaccines in immunocompromised individuals: a systematic review and meta-analysis using the GRADE framework.

Despite representing only 3% of the US population, immunocompromised (IC) individuals account for nearly half of the COVID-19 breakthrough hospitalizations. IC individuals generate a lower immune response after vaccination in general, and the US CDC recommended a third dose of either mRNA-1273 or BNT162b2 COVID-19 vaccines as part of their primary series. Influenza vaccine trials have shown that increasing dosage could improve effectiveness in IC populations. The objective of this systematic literature review and pairwise meta-analysis was to evaluate the clinical effectiveness of mRNA-1273 (50 or 100 mcg/dose) vs BNT162b2 (30 mcg/dose) in IC populations using the GRADE framework. The systematic literature search was conducted in the World Health Organization COVID-19 Research Database. Studies were included in the pairwise meta-analysis if they reported comparisons of mRNA-1273 and BNT162b2 in IC individuals ≥18 years of age; outcomes of interest were symptomatic, laboratory-confirmed SARS-CoV-2 infection, SARS-CoV-2 infection, severe SARS-CoV-2 infection, hospitalization due to COVID-19, and mortality due to COVID-19. Risk ratios (RR) were pooled across studies using random-effects meta-analysis models. Outcomes were also analyzed in subgroups of patients with cancer, autoimmune disease, and solid organ transplant. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Evidence was evaluated using the GRADE framework. Overall, 17 studies were included in the pairwise meta-analysis. Compared with BNT162b2, mRNA-1273 was associated with significantly reduced risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.75-0.97]; P=0.0151; I2=67.7%), severe SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.77-0.93]; P=0.0009; I2=0%), COVID-19-associated hospitalization (RR, 0.88 [95% CI, 0.79-0.97]; P<0.0001; I2=0%), and COVID-19-associated mortality (RR, 0.63 [95% CI, 0.44-0.90]; P=0.0119; I2=0%) in IC populations. Results were consistent across subgroups. Because of sample size limitations, relative effectiveness of COVID-19 mRNA vaccines in IC populations cannot be studied in randomized trials. Based on nonrandomized studies, evidence certainty among comparisons was type 3 (low) and 4 (very low), reflecting potential biases in observational studies. This GRADE meta-analysis based on a large number of consistent observational studies showed that the mRNA-1273 COVID-19 vaccine is associated with improved clinical effectiveness in IC populations compared with BNT162b2.

Real-world effectiveness of COVID-19 vaccines among Colombian adults: A retrospective, population-based study of the ESPERANZA cohort.

COVID-19 vaccines have been essential for reducing the impact of the pandemic; nevertheless, population-based data under real-life conditions are needed to compare their effectiveness in various contexts. The objective of this study was to estimate the effectiveness of vaccines in preventing hospitalization and death from COVID-19 in Colombia under real-life conditions among people aged 18 years and older, according to sex, age, confirmed history of COVID-19 and vaccination series, including the effects of boosters. This investigation was an observational, retrospective, population-based study based on the Colombian cohort "Esperanza". A total of 14,213,409 individuals aged 18 years and older were analyzed, who were matched in a 1:1 ratio of vaccinated to unvaccinated. The study groups consisted of unvaccinated individuals, those with a complete series (CS) and individuals with a CS plus booster. The vaccinated individuals received either homologous or heterologous vaccinations with Ad26.COV2-S, BNT162b2, ChAdOx1 nCoV-19, CoronaVac and mRNA-1273 vaccines. Follow-up was conducted between February 2021 and June 2022. Cox proportional hazards models were used, adjusted for potential confounders, to estimate the effectiveness of different vaccination series. For adults aged 18 years and older, the overall effectiveness of the vaccines in preventing hospitalization was 82.7% (95% CI 82.1-83.2) for CS and 80.2% (95%CI 78.7-81.6) for CS + booster. The effectiveness in preventing death was 86.0% (95%CI 85.5-86.5) for CS and 83.1% (95%CI 81.5-84.5) for CS + booster. Effectiveness decreased with age. While all efficacies were high, CoronaVac offered significantly lower protection, although this improved with a booster. Continued mass vaccination is pivotal, especially in low- and middle-income countries. The study highlights both the real-world effectiveness of these vaccines and the challenges in understanding waning immunity and the influence of different VoC(Variants of Concern) on results.

Relatively preserved functional immune capacity with standard COVID-19 vaccine regimen in people living with HIV.

People living with HIV (PLWH) are at a higher risk of severe disease with SARS-CoV-2 virus infection. COVID-19 vaccines are effective in most PLWH. However, suboptimal immune responses to the standard two-shot regimen are a concern, especially for those with moderate to severe immunodeficiency. An additional dose is recommended as part of the extended primary series in Taiwan. Herein, we study the efficacy of this additional shot in PLWH with mild immunodeficiency compared to that in healthy non-HIV people. In total, 72 PLWH that were asymptomatic or with mild immunodeficiency (CD4 counts ≥200/mm3) and suppressed virology, and 362 healthcare workers of our hospital were enrolled. None of the participants had a history of SARS-CoV-2 infection. They received mRNA-1273 and ChAdOx1 vaccines. Anti-SARS-CoV-2 neutralizing and anti-Spike IgG antibodies, and SARS-CoV-2-specific T cell responses were evaluated. The standard two-shot regimen elicited lower responses in PLWH than the healthcare workers without HIV infection, although the difference was statistically insignificant. They had comparable levels of neutralizing and anti-Spike antibodies and comparable effector CD4+ and CD8+ T cell responses. The third shot boosted the SARS-CoV-2 immunity significantly more with better antibody responses and higher IFN-γ and IL-2 responses of the CD4+ and CD8+ T cells in PLWH compared to those without HIV. Upon in vitro stimulation with extracted Wuhan strain SARS-CoV-2 proteins, CD8+ T cells from PLWH after 3 shots had more durable effector responses than the non-HIV controls with extended time of stimulation. This subtle difference between PLWH and non-HIV people implied immune exhaustion with two shots in non-HIV people. Slightly compromised immunity in PLWH indeed preserved the functional capacity for further response to the third shot or natural infection.

Incidence of multiple sclerosis relapses and pseudo-relapses following COVID-19 vaccination.

The coronavirus disease 2019 (COVID-19) pandemic created an urgency for an effective vaccine. The FDA approved vaccines offered by Pfizer-BioNTech (BNT162b2), ModernaTX (mRNA-1273) and Janssen/Johnson & Johnson (Ad26.COV2.S) have shown minimal side effects (SE) in general population studies. Multiple sclerosis (MS) patients were not specifically represented in the above studies. The MS community is interested in how these vaccines behave in people with MS. In this study, we compare the SE experienced by MS to that of the general population after SARS-CoV-2 vaccination and evaluate their risk of relapses or pseudo-relapses. A retrospective, single-site, cohort study of 250 MS patients who received the initial cycle of FDA approved SARS-CoV-2 vaccines with 151 of whom also received an additional booster dose. SE resulting immediately after COVID-19 vaccination were collected as part of the standard clinical care during patient visits. Out of the studied 250 MS patients, 135 received the first and second doses of BNT162b2 with less than 1% and 4% pseudo-relapses respectively and 79 received the third BNT162b2 dose with a pseudo-relapse rate of 3%. 88 received the mRNA-1273 vaccine with a pseudo-relapse frequency of 2% and 5% after the first and second doses respectively. 70 patients had the mRNA-1273 vaccine booster with a 3% pseudo-relapse rate. 27 received the Ad26.COV2.S first dose, 2 of whom received a second Ad26.COV2.S booster dose, with no reports of MS worsening. No acute relapses were reported in our patient population. All patients experiencing pseudo-relapse symptoms returned to baseline within 96h. COVID-19 vaccine is safe in patients with MS. Cases of temporary worsening of MS symptoms following SARS-CoV-2 are rare. Our findings support those reported by other recent studies and the CDC recommendation for MS patients to receive the FDA-approved COVID-19 vaccines, including the boosters.

Immunogenicity after two and three doses of mRNA vaccine in patients with cancer treated with exclusive radiotherapy.

Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy). Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines. Ninety-two patients were enrolled. With a median of 147days after the second dose, the median SARS-CoV-2 IgG titer was 300 BAU/mL: six patients were seronegative (Spike IgG titer≤40 BAU/mL), whereas 24, 46 and 16 were poor responders (Spike IgG titer:41-200 BAU/mL), responders (Spike IgG titer:201-800 BAU/mL) and ultraresponders (Spike IgG titer>800 BAU/mL), respectively. Among seronegative patients, two patients were negative also for cell mediated response, as tested with IFN-γ release Assay (IGRA) test. With a median of 85days after the third dose, the median SARS-CoV-2 IgG titer was 1632 BAU/mL in 81 patients: only two patients were seronegative, whereas 16 and 63 patients were responders and ultraresponders, respectively. Among the 2 persistently seronegative patients, IGRA test was negative in one who had previously received anti-CD20 therapy. Documented paucisymptomatic (n=3) or asymptomatic (n=4) infection occurred after the third dose, during the Omicron wave. In patients treated with exclusive RT, even during the Omicron breakthrough, robust humoral response and clinical protection from severe SARS-CoV-2 disease were achievable with three doses of mRNA vaccine.

Low incidence of de novo HLA antibodies after COVID-19 vaccination: A cohort study of patients awaiting kidney transplantation.

Antibodies against human leukocyte antigen (anti-HLA Abs) are associated with an increased risk of allograft loss. Herein, we report the prospective follow-up for anti-HLA Abs formation in 103 patients with end-stage kidney disease on the waiting list for transplantation who underwent COVID-19 vaccination. Sera were tested before and after vaccination using Luminex technology. The cohort comprised of 62 males and 41 females with a mean age of 56 ± 14 years. The patients received BNT162b2 (80.4%), mRNA-1273 (18.5%), AZD1222 (0.40%), or ChAdOx1-S (0.80%) vaccine. Patients were tested before and within 119 ± 50, 95 ± 46 and 25 ± 26 days after the first, second, and third dose of the vaccine, respectively. No significant change in calculated panel reactive antibody (cPRA) after vaccination was seen. Although 98.1% of patients had no change in anti-HLA Abs profile or cPRA after vaccination, two patients (1.9%) developed de novo anti-HLA Abs against class I or II HLA antigens. In those two patients, the cPRA changed from 0% and 63% at baseline to 9% and 90% after vaccination, respectively. Both patients received the BNT162b2 mRNA-based vaccine. The earliest detected anti-HLA Abs was 18 days after the first dose. In rare cases, new anti-HLA antibodies were observed after COVID-19 vaccination, with potential implications for transplantation. The low incidence of this phenomenon is outweighed by the clinical benefits of vaccination.

Immunogenicity and safety of NVX-CoV2373 as a booster: A phase 3 randomized clinical trial in adults

BackgroundTo combat the SARS-CoV-2 pandemic, multiple vaccines using different manufacturing platforms have been developed, including NVX-CoV2373 (an adjuvanted recombinant protein vaccine). As SARS-CoV-2 variants have emerged, some of which evade vaccine-induced immunity, introduction of vaccine booster doses has become critical. Employing different vaccine types for primary series vaccination and boosting could expand vaccine coverage and access. This study assessed whether NVX-CoV2373 would induce robust responses when used as a booster. MethodsThe 2019nCoV-307 study was a phase 3, randomized, observer-blinded trial evaluating immunogenicity and safety of NVX-CoV2373 in previously vaccinated adults aged 18–49 years in the United States (NCT05463068). Participants were randomized 1:1:1 to receive one intramuscular injection of NVX-CoV2373 from one of three different manufacturing lots. Immunogenicity was assessed by immunoglobulin G (IgG) and neutralizing antibodies (NAb). These responses were compared for the three lots, and for participants with primary series with or without a prior booster dose of the mRNA-1273, BNT162b2, Ad26.COV2.S, or NVX-CoV2373 COVID-19 vaccines. ResultsA total of 911 participants were randomized between July 11 and 13, 2022, with 905 being assessed for safety and 848 for immunogenicity. Immunogenicity of NVX-CoV2373 met prespecified equivalence criteria between lots, and the booster dose was well-tolerated. NVX-CoV2373 induced robust IgG and NAb responses when used as a first or later booster dose, regardless of primary series vaccine type. Seroconversion rates were also similar across previous vaccine types. Induced antibodies were strongly reactive, even to the immune-evasive Omicron BA.1 and BA.5 variants. ConclusionsNVX-CoV2373 showed consistent immunogenicity between lots, with no new safety signals identified. Use of NVX-CoV2373 as a booster dose (first or later) is supported.

Antibody Response against Severe Acute Respiratory Syndrome Coronavirus 2 Messenger Ribonucleic Acid Vaccines in Infected Individuals: A Systematic Review.

Individuals with a history of coronavirus disease 2019 (COVID-19) exhibit memory immunity acquired during natural infection. However, a decline in immunity after infection renders these individuals vulnerable to re-infection, in addition to a higher risk of infection with new variants. This systematic review examined related studies to elucidate the antibody response in these infected individuals after messenger ribonucleic acid (mRNA) vaccination. Hence, the focus of this review was to ascertain differences in the concentration of binding and neutralising antibodies of previously infected individuals in comparison to those of infection-naïve individuals after administration of two doses of mRNA vaccination through available case-control and cohort studies. Positive reverse transcriptase-polymerase chain reaction (RT-PCR) test or detectable anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies at the baseline in included studies showed categorisation of infected and uninfected individuals. This review utilised three online databases: PubMed, Scopus and Cochrane with the following keywords: (COVID-19 OR 'Coronavirus Disease 2019' OR SARS-CoV-2) AND Immun* AND (Pfizer OR BioNTech OR BNT162b2 OR Comirnaty OR Moderna OR mRNA-1273) from January 2019 to July 2021. Following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) 2020 guidelines and assessment based on the Crowe Critical Appraisal Tool (CCAT), we included 13 related qualified papers of observational studies discerning the binding and neutralising antibody concentrations of infected and uninfected individuals after administration of mRNA vaccines, such as the BNT162b2 and mRNA-1273 vaccine. The mRNA vaccines induced robust binding and neutralising antibody responses in both groups. However, infected individuals showed induction of higher antibody responses in a shorter time compared to uninfected individuals. Hence, a single dose of mRNA vaccination for infected individuals may be sufficient to reach the same level of antibody concentration as that observed in uninfected individuals after receiving two doses of vaccination.

Anti-SARS-CoV-2 (COVID-19) vaccination efficacy in patients with severe neuromuscular diseases

IntroductionPatients with severe neuromuscular disease (sNMD) are considered at high risk of severe COVID-19. Muscle tissue is often replaced by fibroadipose tissue in these diseases whereas the new mRNA-based vaccines are injected intramuscularly. We aimed at evaluating the efficacy of two injections associated with a booster injection of mRNA vaccine in these patients. MethodsWe performed an observational, prospective, single-centre study to investigate the level of anti-S antibodies (Abs) and their neutralization activity at weeks 6 (W6) and 24 (W24) after two injections of mRNA-1273 vaccine and at weeks 12 (BW12) and 29 (BW29) after a booster injection of BNT162b2 vaccine in patients with sNMD. ResultsThirty-three patients with sNMD were included. At W6, 30 patients (90.1%) showed a protective serum level of specific anti-S Abs with a strong neutralization capacity. We observed a decline over time: only 12 patients (36.3%) retained anti-S Abs levels considered as protective at W24. The neutralization activity remained above the cut off in 23 (69.7%). The booster vaccination restored robust neutralization activity for all analysed 22 patients (100%) at BW12, which was maintained without any significant drop at BW29 (16). No severe adverse event was reported in this cohort and none of the 33 patients developed symptomatic COVID-19 over one year. ConclusionsThis study provides evidence that most sNMD patients receiving two injections of COVID-19 mRNA-based vaccines develop a strong humoral response after vaccination. A decline over time was observed but a single booster injection restores a long-term immunity. Moreover, no safety issues were observed.

Characterization of Immunogenicity and Safety of COVID-19 mRNA-1273 in HIV-Positive Italian Patients with Hemophilia: A Prospective Single-Center Cohort Study.

To characterize the immunogenicity of mRNA-1273 (Moderna, Cambridge, MA, USA) vaccine in HIV-positive hemophilic patients during the third COVID-19 wave in Italy and to investigate biomarkers of coagulation and endothelial perturbation before and after complete vaccination schedule, twenty-three consecutive adult HIV-positive patients with hemophilia were included. Blood was collected before and two weeks after vaccination. We measured anti-SARS-CoV-2 spike protein antibodies to assess immunogenicity; circulating biomarkers of coagulation (protein C and D-dimer), endothelial perturbation (von Willebrand factor (VWF)) and anti-Platelet Factor 4 (PF4) antibodies were analyzed. Flow-based analysis of thrombus formation was performed in nine patients using a flow-chamber device. Two weeks after completing the vaccination schedule, all patients had anti-spike antibodies values consistent with an effective immunization. Mean (±standard deviation) basal values of protein C and VWF (106 ± 21% and 171 ± 45%, respectively) were not significantly different from data obtained two weeks after the second dose (103 ± 20%, 162 ± 43%, respectively). D-dimer median values (interquartile range) were not significantly different at baseline (442 (603-142) ng/mL) and after the second dose (477 (654-262) ng/mL). Anti-PF4 antibodies were detected in three patients with no associated clinical manifestations. No significant differences were found in flow-based analysis of thrombus formation. Our data demonstrate that in HIV-positive patients with hemophilia, SARS-CoV-2 vaccination is effective and safe, with no effects on coagulation and endothelial perturbation.

Comparison, by Country, of the Uptake of COVID-19 Vaccination by Health Care Workers in the EU/EEA, January – June 2021

Aims: The aim of this study was to compare, by country, COVID-19 vaccination uptake by Health Care Workers (HCWs) from January to June 2021, to assist with policy making and prospective planning in these countries during the COVID-19 pandemic and into the future. Background: Health Care Workers (HCWs) are at high risk of exposure to COVID-19 when providing care to patients. We investigated the uptake of COVID-19 vaccination among HCWs in the EU/EEA and discussed the factors which influence this uptake. Methods: The study population included all the countries in the European Union (EU) and European Economic Area (EEA). The secondary data file was downloaded from the European Centre for Disease Prevention and Control (ECDC) website. Descriptive and comparative data were analysed and presented using Excel and Chi-square test of hypothesis. Results: The proportion of HCWs in EU/EEA countries ranged from 1.2% to 5.1% per population. From January to June 2021, the proportion of first and second dose vaccinations of HCWs ranged from 20% to 100% and from 21% to 100%, respectively. The Comirnaty–Pfizer/BioNTech vaccine (COM) was the most administered vaccine in all EU/EEA countries, followed by the Moderna mRNA-1273 vaccine (MOD) and the Astra-Zeneca–Vaxzevria vaccine (AZ). In January 2021, a median of 29% of HCWs received their first dose of COVID-19 vaccination. Italy was the only country with a mandatory vaccination policy for HCWs. Vaccination uptake rates were statistically different among EU countries (p&lt;0.05). Conclusion: Data such as these could be used in mathematical modelling potential future pandemics to predict vaccine up-take by selected, exposed, vulnerable sectors of the population, for whom it is relevant.

STAR SIGN study: Evaluation of COVID-19 vaccine efficacy against the SARS-CoV-2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease.

Vaccine-elicited immune responses are impaired in patients with inflammatory bowel disease (IBD) treated with anti-TNF biologics. To assess vaccination efficacy against the novel omicron sublineages BQ.1.1 and XBB.1.5 in immunosuppressed patients with IBD. This prospective multicentre case-control study included 98 biologic-treated patients with IBD and 48 healthy controls. Anti-spike IgG concentrations and surrogate neutralisation against SARS-CoV-2 wild-type, BA.1, BA.5, BQ.1.1, and XBB.1.5 were measured at two different time points (2-16 weeks and 22-40 weeks) following third dose vaccination. Surrogate neutralisation was based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Primary outcome was surrogate neutralisation against tested SARS-CoV-2 sublineages. Secondary outcomes were proportions of participants with insufficient surrogate neutralisation, impact of breakthrough infection, and correlation of surrogate neutralisation with anti-spike IgG concentration. Surrogate neutralisation against all tested sublineages was reduced in patients with IBD who were treated with anti-TNF biologics compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.001) at visit 1. Anti-TNF therapy (odds ratio 0.29 [95% CI 0.19-0.46]) and time since vaccination (0.85 [0.72-1.00]) were associated with low, and mRNA-1273 vaccination (1.86 [1.12-3.08]) with high wild-type surrogate neutralisation in a β-regression model. Accordingly, higher proportions of patients treated with anti-TNF biologicshad insufficient surrogate neutralisation against omicron sublineages at visit 1 compared to patients treated with non-anti-TNF biologics and healthy controls (each p ≤ 0.015). Surrogate neutralisation against all tested sublineages decreased over time but was increased by breakthrough infection. Anti-spike IgG concentrations correlated with surrogate neutralisation. Patients with IBD who are treated with anti-TNF biologics show impaired neutralisation against novel omicron sublineages BQ.1.1 and XBB.1.5 and may benefit from prioritisation for future variant-adapted vaccines.

Persistence of antibody responses to COVID-19 vaccines among participants in the COVID-19 Community Research Partnership

IntroductionHigh levels of immunity to SARS-CoV-2 in the community correlate with protection from COVID-19 illness. Measuring COVID-19 antibody seroprevalence and persistence may elucidate the level and length of protection afforded by vaccination and infection within a population. MethodsWe measured the duration of detectable anti-spike antibodies following COVID-19 vaccination in a multistate, longitudinal cohort study of almost 13,000 adults who completed daily surveys and submitted monthly dried blood spots collected at home. ResultsOverall, anti-spike antibodies persisted up to 284 days of follow-up with seroreversion occurring in only 2.4% of the study population. In adjusted analyses, risk of seroreversion increased with age (adults aged 55–64: adjusted hazard ratio [aHR] 2.19 [95% confidence interval (CI): 1.22, 3.92] and adults aged > 65: aHR 3.59 [95% CI: 2.07, 6.20] compared to adults aged 18–39). Adults with diabetes had a higher risk of seroreversion versus nondiabetics (aHR 1.77 [95% CI: 1.29, 2.44]). Decreased risk of seroreversion was shown for non-Hispanic Black versus non-Hispanic White (aHR 0.32 [95% CI: 0.13, 0.79]); college degree earners versus no college degree (aHR 0.61 [95% CI: 0.46, 0.81]); and those who received Moderna mRNA-1273 vaccine versus Pfizer-BioNTech BNT162b2 (aHR 0.35 [95% CI: 0.26, 0.47]). An interaction between healthcare worker occupation and sex was detected, with seroreversion increased among male, non-healthcare workers. ConclusionWe established that a remote, longitudinal, multi-site study can reliably detect antibody durability following COVID-19 vaccination. The survey platform and measurement of antibody response using at-home collection at convenient intervals allowed us to explore sociodemographic factors and comorbidities and identify predictors of antibody persistence, which has been demonstrated to correlate with protection against disease. Our findings may help inform public health interventions and policies to protect those at highest risk for severe illness and assist in determining the optimal timing of booster doses.Clinical trials registry: NCT04342884.

Comparative Risks of Potential Adverse Events Following COVID-19 mRNA Vaccination Among Older US Adults

Head-to-head safety comparisons of the mRNA vaccines for SARS-CoV-2 are needed for decision making; however, current evidence generalizes poorly to older adults, lacks sufficient adjustment, and inadequately captures events shortly after vaccination. Additionally, no studies to date have explored potential variation in comparative vaccine safety across subgroups with frailty or an increased risk of adverse events, information that would be useful for tailoring clinical decisions. To compare the risk of adverse events between mRNA vaccines for COVID-19 (mRNA-1273 and BNT162b2) overall, by frailty level, and by prior history of the adverse events of interest. This retrospective cohort study was conducted between December 11, 2020, and July 11, 2021, with 28 days of follow-up following the week of vaccination. A novel linked database of community pharmacy and Medicare claims data was used, representing more than 50% of the US Medicare population. Community-dwelling, fee-for-service beneficiaries aged 66 years or older who received mRNA-1273 vs BNT162b2 as their first COVID-19 vaccine were identified. Data analysis began on October 18, 2022. Dose 1 of mRNA-1273 vs BNT162b2 vaccine. Twelve potential adverse events (eg, pulmonary embolism, thrombocytopenia purpura, and myocarditis) were assessed individually. Frailty was measured using a claims-based frailty index, with beneficiaries being categorized as nonfrail, prefrail, and frail. The risk of diagnosed COVID-19 was assessed as a secondary outcome. Generalized linear models estimated covariate-adjusted risk ratios (RRs) and risk differences (RDs) with 95% CIs. This study included 6 388 196 eligible individuals who received the mRNA-1273 or BNT162b2 vaccine. Their mean (SD) age was 76.3 (7.5) years, 59.4% were women, and 86.5% were White. A total of 38.1% of individuals were categorized as prefrail and 6.0% as frail. The risk of all outcomes was low in both vaccine groups. In adjusted models, the mRNA-1273 vaccine was associated with a lower risk of pulmonary embolism (RR, 0.96 [95% CI, 0.93-1.00]; RD, 9 [95% CI, 1-16] events per 100 000 persons) and other adverse events in subgroup analyses (eg, 11.0% lower risk of thrombocytopenia purpura among individuals categorized as nonfrail). The mRNA-1273 vaccine was also associated with a lower risk of diagnosed COVID-19 (RR, 0.86 [95% CI, 0.83-0.87]), a benefit that was attenuated by frailty level (frail: RR, 0.94 [95% CI, 0.89-0.99]). In this cohort study of older US adults, the mRNA-1273 vaccine was associated with a slightly lower risk of several adverse events compared with BNT162b2, possibly due to greater protection against COVID-19. Future research should seek to formally disentangle differences in vaccine safety and effectiveness and consider the role of frailty in assessments of COVID-19 vaccine performance.

Humoral and cellular immunity in three different types of COVID-19 vaccines against SARS-CoV-2 variants in a real-world data analysis.

An effective vaccine response is currently a critical issue in the control of COVID-19. Little is known about humoral and cellular immunity comparing protein-based vaccine with other types of vaccines. The relevance of basal immunity to antibody production is also unknown. Seventy-eight individuals were enrolled in the study. The primary outcome were the level of spike-specific antibodies and neutralizing antibodies measured by ELISA. Secondary measures included memory T cells and basal immunity estimated by flow cytometry and ELISA. Correlations for all parameters were calculated using the nonparametric Spearman correlation method. We observed that two doses of mRNA-based Moderna mRNA-1273 (Moderna) vaccine produced the highest total spike-binding antibody and neutralizing ability against the wild-type (WT), Delta, and Omicron variants. The protein-based MVC-COV1901 (MVC) vaccine developed in Taiwan produced higher spike-binding antibodies against Delta and Omicron variants and neutralizing ability against the WT strain than the adenovirus-based AstraZeneca-Oxford AZD1222 (AZ) vaccine. Moderna and AZ vaccination produced more central memory T cells in PBMC than the MVC vaccine. However, the MVC vaccine had the lowest adverse effects compared to the Moderna and AZ vaccines. Surprisingly, the basal immunity represented by TNF-α, IFN-γ, and IL-2 prior to vaccination was negatively correlated with the production of spike-binding antibodies and neutralizing ability. This study compared memory T cells, total spike-binding antibody levels, and neutralizing capacity against WT, Delta, and Omicron variants between the MVC vaccine and the widely used Moderna and AZ vaccines, which provides valuable information for future vaccine development strategies.

Vaccination is the most effective and best way to avoid the disease of COVID-19.

Most of the vaccines that are effective against SARS-CoV-2 have used the following functional strategies: inactivated viruses, live attenuated viruses, viral vector-based vaccines, subunit vaccines, recombinant proteins, and DNA/RNA vaccines. Among the vaccines that stimulate the host's immune system with the help of DNA are: undergoing Phase 2/3 trials including INO-4800 (International Vaccine Institute; Inovio Pharmaceuticals), Symvivo, Canada-COVID19 (AnGes, Inc.); GX-19 (Genexine, Inc.). BNT162b2and mRNA-1273 vaccines were made by BioNTech/Pfizer/Fosun Pharma group and Moderna/NIAID group, respectively, which are considered as types of RNA vaccines. Vaccines that are based on the viral vector are AstraZeneca, Sputonium, and Johnson-Jensen. Among the inactive viral vaccines, the following can be mentioned: CoronaVac (Sinovac) WIBP vaccine (Wuhan Institute of Biological Products, Sinopharm), BBIBPCorV (Beijing Institute of Biological Products, Sinopharm), BBV152/Covaxin (Bharat Biotech, ICMR, National Institute of Virology) And among the protein-based/subunit vaccines, the following can be counted: NVX-CoV2373: (Novavax); SCB-2019 vaccine (Clover Biopharmaceuticals AUS Pty Ltd.); Covax-19 (GeneCure Biotechnologies; Vaxine Pty Ltd.) mRNA vaccines, viral vector vaccines, and protein subunit vaccines cannot cause disease because these vaccines stimulate the immune system to produce antibodies against virus proteins instead of the virus itself (or its antigen). MRNA vaccines increase SARS-CoV-2 proteins and ultimately stimulate the production of T and B lymphocytes. The epidemic of HCoVs and their destructive and harmful effects on life has caused the scientific community to seek the production of an effective and efficient vaccine before its catastrophic release. We all need to know that none of us will be healed until the other is healed. The purpose of this review article is to present a selection of existing knowledge in the field of fighting and preventing the coronavirus.

Robust antibody response after the third mRNA coronavirus vaccination in Japanese hemodialysis patients

BackgroundHemodialysis patients have chronic kidney disease, are often elderly, and have many complications such as hypertension, type 2 diabetes, cardiac disease, and cerebrovascular disease. Therefore, hemodialysis patients infected with COVID-19 are prone to severe disease. Vaccination is the most promising means of preventing the onset and reducing the severity of COVID-19. However, many reports have found that anti-spike antibody titers after two doses of mRNA vaccine are lower in hemodialysis patients than in healthy controls. For this reason, a third vaccination is recommended for hemodialysis patients. In Japan, there are several reports of a third vaccination, especially for hemodialysis patients. In this study, we also examined the antibody response to COVID-19 vaccine in Japanese hemodialysis patients who received the third dose of the vaccine.MethodsStudy participants received a third vaccination (257 with BNT162b2 vaccine and 5 with mRNA-1273 vaccine) approximately 7–9 months after the second (BNT162b2 vaccine). Anti-SARS-CoV-2 spike IgG antibody titers were measured (Abbott SARS-CoV-2 IgG II Quan) in 185 hemodialysis patients and 109 healthcare workers approximately 2 weeks after the second vaccination and in 162 hemodialysis patients and 100 healthcare workers approximately 2 weeks after the third.ResultsFollowing the second vaccination, 97.6% of the hemodialysis group and 100% of the control group were positive for the anti-spike antibody. The median level of the anti-spike antibody was 2728.7 AU/mL (IQR, 1024.2–7688.2 AU/mL) in the hemodialysis group and 10,500 AU/ml (IQR, 9346.1–2,4500 AU/mL) in the controls. Following the third vaccination, 99.4% of the hemodialysis group (only one person tested negative for the antibody) and 100% of the control group were positive for the anti-spike antibody. The median level of the anti-spike antibody was 20,000 AU/mL (IQR, 7729–37,000 AU/mL) in the hemodialysis group and 21,500 AU/ml (IQR, 14,000–32,250 AU/mL) in the control group. The factors involved in the low response to the BNT152b2 vaccine after the second vaccination included old age, low BMI, low Cr index, low nPCR, low GNRI, low lymphocyte count, steroid administration, and complications related to blood disorders. However, in hemodialysis patients, the response after the third vaccination was excellent, and all factors associated with the suppressed response to these vaccines were no longer significant.ConclusionsThe humoral response of hemodialysis patients to two doses of mRNA vaccine was weaker than that of healthy controls. However, a third vaccination eliminated that difference.

Establishing immunogenicity and safety of needle-free intradermal delivery by nanoporous ceramic skin patch of mRNA SARS-CoV-2 vaccine as a revaccination strategy in healthy volunteers

IntroductionNanoporous microneedle arrays (npMNA) are being developed as skin patches for vaccine delivery. As alternative for needle-based immunisation, they may potentially result in higher vaccine acceptance, which is important for future mass vaccination campaigns to control outbreaks, such as COVID-19, and for public vaccination in general. In this study we investigated the safety and immunogenicity of needle-free intradermal delivery of a fractional third or fourth dose of mRNA-1273 vaccine by npMNA. MethodsThis study was an open-label, randomised-controlled, proof-of-concept study. Healthy adults were eligible if they had received a primary immunisation series against SARS-CoV-2 with two doses of mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) mRNA vaccine. A history of a COVID-19 infection or booster vaccination with mRNA-1273 or BNT162b2 was allowed if it occurred at least three months before inclusion. Participants were randomised in a 1:1 ratio to receive 20 µg mRNA-1273 vaccine, either through npMNA patch applied on the skin (ID-patch group), or through intramuscular (IM) injection (IM-control group). Primary outcomes were reactogenicity up to two weeks after vaccination, and fold-increase of SARS-CoV-2 spike S1-specific IgG antibodies 14 days post-vaccination. ResultsIn April 2022, 20 participants were enroled. The geometric mean concentration (GMC) did not increase in the ID-patch group after vaccination, in contrast to the IM-control group (GMC was 1,006 BAU/mL (95% CI 599–1,689), 3,855 (2,800–5,306), and 3,513 (2,554–4,833) at day 1, 15 and 29, respectively). In addition, SARS-CoV-2-specific T cell responses were lower after ID vaccination through npMNA. ConclusionNeedle-free delivery of 20 µg mRNA-1273 vaccine by npMNA failed to induce antibody and T cell responses. As this is a potentially very useful vaccination method, it is important to determine which adjustments are needed to make this npMNA successful. Clinical trial registry (on ClinicalTrial.gov)NCT05315362.