Comparative analysis of BNT162b2, mRNA-1273 and ChAdOx1 COVID-19 vaccine induced antibody responses and the 3rd BNT162b2 vaccine induced neutralizing antibodies against Delta and Omicron variants

Two COVID-19 mRNA and two adenovirus vector vaccines have been licensed in Europe and various vaccine combinations and dosing strategies have been exploited to maximize the immunity against COVID-19. Here, we show that among health care workers (n=328) two doses of BNT162b2, mRNA-1273, or ChAdOx1 as also a combination of an adenovirus vector and mRNA vaccines induces equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against B.1 and B.1.617.2 when administrated with a long 12-week dose interval. Two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies compared to the long interval. Third mRNA vaccine dose for the short dose interval group increased the antibody levels 4-fold compared to the levels after the second dose. Importantly, sera from all three-times vaccinated neutralized B.1.1.529 (Omicron). The data indicates that a third COVID-19 mRNA vaccine dose efficiently induces cross-protective neutralizing antibodies against multiple variants.

SARS-CoV-2 Post Vaccinated Adverse Effects and Efficacy in the Egyptian Population

Vaccines are the solution to overcome SARS-CoV-2. This study aimed to determine the post-Sinopharm vaccine safety-profile and immunity through antibody titers. Data were collected using a structured questionnaire from Egyptian participants who received two doses of Sinopharm vaccine. Data were divided into three parts, the first and second parts were to detect participants’ post-first and second dose symptoms and practices, and the third for the results of IgG anti spike protein antibodies test and laboratory tests. Pain, redness, swelling at the injection site, headache, fatigue, and lethargy were the most common post-vaccine symptoms for both first and second doses. Most of the participants felt mild or no symptoms after vaccination. The symptoms started mostly during the first day post-vaccination and lasted for no more than two days. Forty-nine percent of the participants resulted in positive antibodies tests on day 18 post-vaccination. The average antibody level for vaccinated participants with past SARS-CoV-2 infection was much higher than that for non-past infected participants. These vaccines’ administration methods need to be reevaluated by changing the dose, dose interval, adding a third dose, or mixing it with other vaccines with different techniques to improve their protection rates. Further studies are required to validate this finding.

Safety, Tolerability and Immunogenicity of Oxford-AstraZeneca ChAdOx1 Vaccine Among Polish School-Teachers

Background Polish teachers, as the priority group, were offered the ChAdOx1-S vaccine since February 2021. The objective was to investigate safety, tolerability and immunogenicity of this vaccine following two vaccine doses. Methods Teachers were invited for serological testing ≥8 weeks after second vaccination. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: ≥7.1 BAU/ml). Multivariable logistic regression methods were used to identify predictors of immunogenicity. Results Of 192 teachers, mean age 50.5±8.3 years, 83.9% were females. Median (range) dosing interval was 50 (14-95) days; median interval between the second dose and immunogenicity test was 69 days (range: 57–111). More than a half of teachers (58.3%) reported they would change the product for another (mostly mRNA) vaccine if there was such an opportunity. Adverse reactions after receiving the vaccine (either the first or the second dose) were reported by 79.2% teachers, more frequently after the first dose (84.9%), and were similar in nature to those previously reported: feeling feverish (44.8%), headache (41.7%), malaise, chills (both: 38.0%), injection-site tenderness (37.5%) and pain (32.3%). Less males than females (54.8% vs 80.1%) and older (aged ≥50 years) than younger teachers (65.7% vs 90.4%) reported side effects (p<0.002; p<0.0001, respectively). By ≥8 weeks after the boost dose, all teachers had neutralizing antibody responses. The median (range) anti-spike IgG reading was 525.0 BAU/mL (20.6-5680.0 BAU/mL); 1008.02 (115.3–5680.0) BAU/mL in teachers with evidence of prior infection and 381.42 BAU/mL (20.6–3108.8) in those without (p=0.001). Previous infection with SARS-CoV-2 and longer dose interval were both positive predictors of higher immunologic response (p<0.0001; p=0.01, respectively), with no evidence of differences by age, gender, BMI, smoking or comorbidities. Conclusions The results demonstrated good safety, tolerability and immunogenicity of the ChAdOx1-S vaccine. Immunization led to detectable anti-spike antibodies in all teachers. Our study justifies the longer dose interval as an important factor to enhance higher antibody response. Findings suggest that in immunocompetent vaccine recipients with an evidence of previous infection a delay regarding the second dose could be considered when careful management in the use of vaccine resources is needed.

Epidemiology of myocarditis and pericarditis following mRNA vaccines in Ontario, Canada: by vaccine product, schedule and interval

ImportanceIncreased rates of myocarditis/pericarditis following COVID-19 mRNA vaccines have been observed. However, little data are available related to product-specific differences, which have important programmatic impacts.ObjectiveThe objective of this study was to estimate reporting rates of myocarditis/pericarditis following COVID-19 mRNA vaccine by product, age, sex, and dose number, as well inter-dose interval.DesignWe conducted a population-based cohort study using passive vaccine safety surveillance data. All individuals in Ontario, Canada who received at least one dose of COVID-19 mRNA vaccine between December 14, 2020 and September 4, 2021 were included.SettingThis study was conducted in Ontario, Canada (population: 14.7 million) using the provincial COVID-19 vaccine registry and provincial adverse events following immunization database.ParticipantsWe included all individuals with a reported episode of myocarditis/pericarditis following COVID-19 vaccine in the study period. We obtained information on all doses administered in the province to calculate reporting rates.ExposureReceipt of COVID-19 mRNA vaccine (mRNA-1273 [Moderna Spikevax] or BNT162b2 [Pfizer-BioNTech Comirnaty]).Main Outcome(s) and Measure(s)Reported rate of myocarditis/pericarditis meeting level 1-3 of the Brighton Collaboration case definitions.ResultsThere were 19,740,741 doses of mRNA vaccines administered and 297 reports of myocarditis/pericarditis meeting our inclusion criteria. Among these, 69.7% occurred following the second dose of COVID-19 mRNA vaccine and 76.8% occurred in males. The median age of individuals with a reported event was 24 years. The highest reporting rate of myocarditis/pericarditis was observed in males aged 18-24 years following mRNA-1273 as the second dose; the rate in this age group was 5.1 (95% CI 1.9-15.5) times higher than the rate following BNT162b2 as the second dose. Overall reporting rates were higher when the inter-dose interval was shorter (i.e., ≤30 days) for both vaccine products. Among individuals who received mRNA-1273 for the second dose, rates were higher for those who had a heterologous as opposed to homologous vaccine schedule.Conclusions and RelevanceOur results suggest that vaccine product, inter-dose interval and vaccine schedule combinations may play a role in the risk of myocarditis/pericarditis, in addition to age and sex. Certain programmatic strategies could reduce the risk of myocarditis/pericarditis following mRNA vaccines.

Serological responses and vaccine effectiveness for extended COVID-19 vaccine schedules in England

The UK prioritised delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval between doses up to 12 weeks. In 750 participants aged 50–89 years, we here compare serological responses after BNT162b2 and AZD1222 vaccination with varying dose intervals, and evaluate these against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. We show that antibody levels 14–35 days after dose two are higher in BNT162b2 recipients with an extended vaccine interval (65–84 days) compared with those vaccinated with a standard (19–29 days) interval. Following the extended schedule, antibody levels were 6-fold higher at 14–35 days post dose 2 for BNT162b2 than AZD1222. For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with dose interval. Higher dose two VE was observed with >6 week interval between BNT162b2 doses compared to the standard schedule. Our findings suggest higher effectiveness against infection using an extended vaccine schedule. Given global vaccine constraints these results are relevant to policymakers.

Reduced Dosing Frequency Following a Switch to Rix-FP for the Treatment of Hemophilia B: Results from the Athn 2 Study

Introduction: The approval of extended half-life recombinant factor IX (rFIX) replacement products has expanded the range of therapeutic options available for the treatment of hemophilia B. Compared with standard half-life FIX, these products allow for extended dosing intervals while maintaining appropriate bleed control. One such extended half-life product is rIX-FP (IDELVION; CSL Behring), a recombinant fusion protein linking rFIX with recombinant albumin, offering the possibility of dosing up to every 21 days in adults. The ATHN 2: Factor Switching Study provides information on patient outcomes following a switch from a previous FIX product to rIX-FP. Methods: ATHN 2 was a factor-switching study sponsored by the American Thrombosis and Hemostasis Network (ATHN) conducted in participants across the US hemophilia treatment center (HTC) network. This was a multi-center, longitudinal, observational study with two arms: a prospective arm following participants for up to one year after switching factor replacement product, and a retrospective arm including participants who have switched products within the 50 weeks prior to enrollment with retrospective and/or prospective assessment for up to one year. Male and female children and adults (≥2 years) with FIX clotting activity ≤5% of normal who had previously been treated with plasma-derived or recombinant FIX for at least 50 exposure days were eligible for inclusion. Treatment was administered at the discretion of the participant's hemophilia caregiver. Data was collected at study/clinic visits, or via a telephone interview conducted every three months. Baseline demographic data was collected for all participants. The prescribed dosing frequency for each participant was collected before and after the switch to rIX-FP, including dosing frequency taken from the first and last treatment records taken during the study following the switch. Participants were also asked to rank their satisfaction with rIX-FP upon the completion or early termination of the study. Results: A total of 41 participants were included in this analysis; 27 in the prospective arm and 14 in the retrospective arm. The mean (SD) age across all participants was 22.5 (17.1) years, ranging from 2 to 71 years. The median age was 18 years old and most participants had severe hemophilia B (FIX activity &lt;1%; n=26, 63%). Prior to the switch to rIX-FP, 76% (n=31) of participants were receiving prophylaxis and 24% (n=10) received episodic treatment. The majority of participants (62%) receiving prophylaxis were treated twice a week (Table 1). Following the treatment switch, 93% of participants were initially assigned to a once-weekly or less frequent dosing regimen. This proportion remained stable over the course of the study, with 89% of participants on once-weekly or less frequent prophylaxis by the time of the last record taken. Among 23 participants with complete data on their prophylaxis dose interval before and after treatment switch, 70% of the participants were able to extend their dose frequency and maintain the extended dose frequency through the study. Thirty-seven participants responded to the satisfaction survey, with the majority (n=33, 89%) being somewhat or very satisfied with rIX-FP treatment. Conclusions: Switching to rIX-FP allowed participants to extend their prophylaxis dosing interval and a majority of participants were able to maintain the extended dose interval through the study period. In addition, a majority of participants were satisfied with rIX-FP treatment, altogether suggesting that extended half-life factor replacement with rIX-FP offers a valuable treatment option for hemophilia B. Figure 1 Figure 1. Disclosures Journeycake: HEMA Biologics: Honoraria; LFB: Honoraria. Chrisentery-Singleton: Biomarin: Speakers Bureau; Kedrion: Consultancy; Takeda: Consultancy, Speakers Bureau; Spark: Consultancy, Research Funding; Sanofi: Consultancy; Pfizer: Consultancy, Research Funding, Speakers Bureau; Octapharma: Consultancy; Novo Nordisk: Consultancy, Speakers Bureau; Hema Biologics: Consultancy; Grifols: Consultancy; Genentech: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau. Desai: CSL Behring: Current Employment. von Drygalski: Pfizer: Research Funding; Novo Nordisk: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hematherix, Inc: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Super FVa; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL Behring: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biomarin: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; uniQure: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Patel: CSL Behring: Current Employment. Raffini: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Bayer: Consultancy; XaTek: Consultancy. Recht: Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; uniQure: Consultancy; Takeda: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy; Octapharma: Consultancy; Novo Nordisk: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Genentech: Consultancy; CSL Behring: Consultancy; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Catalyst Biosciences: Consultancy. Sidinio: Biomarin: Consultancy; Takeda: Consultancy, Research Funding; Pfizer: Consultancy; Novo Nordisk: Consultancy; Bayer: Consultancy; Guardian Therapeutics: Consultancy; Octapharma: Consultancy, Research Funding; Genentech/Roche: Consultancy, Research Funding; Catalyst: Consultancy. Wang: Bayer: Consultancy; Biomarin: Consultancy; CSL Behring: Consultancy; Genentech: Consultancy; Hema Biologics: Consultancy; Novo Nordisk: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy. Zhang: CSL Behring: Current Employment, Current holder of individual stocks in a privately-held company. Neufeld: Pfizer: Consultancy; Chiesi: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Octapharma: Consultancy, Research Funding; Acceleron Pharma: Consultancy; Baxter: Consultancy; Shire: Consultancy; Takeda: Consultancy; CSL: Consultancy; Biogen: Consultancy; Novo Nordisk: Consultancy; Bristol Myers-Squibb: Consultancy; ATHN: Research Funding; Celgene: Research Funding.

Effectiveness of ChAdOx1 vaccine in older adults during SARS-CoV-2 Gamma variant circulation in São Paulo

A two-dose regimen of the Oxford-AstraZeneca (ChAdOx1) Covid-19 vaccine with an inter-dose interval of three months has been implemented in many countries with restricted vaccine supply. However, there is limited evidence for the effectiveness of ChAdOx1 by dose in elderly populations in countries with high prevalence of the Gamma variant of SARS-CoV-2. Here, we estimate ChAdOx1 effectiveness by dose against the primary endpoint of RT-PCR-confirmed Covid-19, and secondary endpoints of Covid-19 hospitalization and Covid-19-related death, in adults aged ≥60 years during an epidemic with high Gamma variant prevalence in São Paulo state, Brazil using a matched, test-negative case-control study. Starting 28 days after the first dose, effectiveness of a single dose of ChAdOx1 is 33.4% (95% CI, 26.4–39.7) against Covid-19, 55.1% (95% CI, 46.6–62.2) against hospitalization, and 61.8% (95% CI, 48.9–71.4) against death. Starting 14 days after the second dose, effectiveness of the two-dose schedule is 77.9% (95% CI, 69.2–84.2) against Covid-19, 87.6% (95% CI, 78.2–92.9) against hospitalization, and 93.6% (95% CI, 81.9–97.7) against death. Completion of the ChAdOx1 vaccine schedule affords significantly increased protection over a single dose against mild and severe Covid-19 outcomes in elderly individuals during widespread Gamma variant circulation.

Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review

Given the typical age onset of schizophrenia, there are tremendous economic and social impacts that extend beyond the person and their families. One critical determinant of the diseases' impact is the patient's adherence to antipsychotic drug treatment. Approved in 2015 for the treatment of schizophrenia, paliperidone palmitate (Invega Trinza, a 3-month injection, noted as PP3M) is a second-generation long-acting injectable antipsychotic medication. Among the different formulations offered for palmitate paliperidone, including the 1 and 3-month formulations, the longer duration 3-month formulation was better at preventing relapse in schizophrenic patients. To date, different formulations of palmitate paliperidone that have been studied on relapse episodes of schizophrenia include once-daily extended-release oral paliperidone (ORAL paliperidone), once-monthly paliperidone palmitate (PP1M), and once-every-3-months paliperidone palmitate (PP3M). Post-hoc analyses show that patients who were withdrawn from PP1M paliperidone had the least risk of relapse, followed by patients withdrawn from PP3M and patients withdrawn from ORAL paliperidone. PP3M was better at preventing relapse compared to ORAL paliperidone. The results demonstrated that 50% of patients who were withdrawn from ORAL paliperidone, PP1M, or PP3M remained relapse-free for ~2, 6, and 13 months, respectively. Compared to PP1M, PP3M is just as safe and effective and has the added advantage of increased adherence related to a longer dose interval, decreasing the risk of relapse.