Primary Dose Research Articles

An optimization model with simulation for optimal regional allocation of COVID-19 vaccines

In response to the coronavirus disease 2019 (COVID-19) pandemic, the allocation of vaccines has become a crucial undertaking, particularly in the Philippines. The efficient distribution of vaccines across different regions remains vital. In this study, we present an approach to determine the optimal allocation of COVID-19 vaccines in the Philippines, leveraging actual data on the supply of vaccines per region for different brands. A notable advantage of our work, compared to existing models, is the comprehensive consideration of crucial factors, including vaccine effectiveness, waning immunity, various age groups, population data, and weekly vaccination rates. We formulate a linear programming model with the objective of minimizing both the primary and breakthrough infections. Several constraints are incorporated into the model, including vaccine supply, the size of the eligible population, weekly vaccination rates, and the interval between vaccine doses set by the Philippine government. Our findings show that prioritizing the pediatric population (aged 5 to 11) for the primary vaccination series within the initial three months is vital. Administering first booster shots to those aged 12 and older during this period is also recommended. Numerical results indicate a preference for highly effective vaccine brands in regions with a high COVID-19 incidence proportion. Conversely, vaccines with lower effectiveness are suitable for primary doses in regions with low COVID-19 cases. This research provides an analytical approach in addressing the complexities of COVID-19 vaccine distribution and allocation. It offers essential guidance to policymakers in the Philippines, enhancing population protection, and contributing to economic recovery.

Adverse Events Following the BNT162b2 mRNA COVID-19 Vaccine (Pfizer-BioNTech) in Aotearoa New Zealand.

In February 2021, New Zealand began its largest ever immunisation programme with the BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine. We aimed to understand the association between 12 adverse events of special interest (AESIs) and a primary dose of BNT162b2 in the New Zealand population aged ≥5 years from 19 February 2021 through 10 February 2022. Using national electronic health records, the observed rates of AESIs within a risk period (1-21 days) following vaccination were compared with the expected rates based on background data (2014-2019). Standardised incidence ratios (SIRs) were estimated for each AESI with 95% confidence intervals (CIs) using age group-specific background rates. The risk difference was calculated to estimate the excess or reduced number of events per 100,000 persons vaccinated in the risk period. As of 10 February 2022, 4,277,163 first doses and 4,114,364 second doses of BNT162b2 had been administered to the eligible New Zealand population aged ≥5 years. The SIRs for 11 of the 12 selected AESIs were not statistically significantly increased post vaccination. The SIR (95% CI) for myo/pericarditis following the first dose was 2.3 (1.8-2.7), with a risk difference (95% CI) of 1.3 (0.9-1.8), per 100,000 persons vaccinated, and 4.0 (3.4-4.6), with a risk difference of 3.1 (2.5-3.7), per 100,000 persons vaccinated following the second dose. The highest SIR was 25.6 (15.5-37.5) in the 5-19 years age group, following the second dose of the vaccine, with an estimated five additional myo/pericarditis cases per 100,000 persons vaccinated. A statistically significant increased SIR of single organ cutaneous vasculitis (SOCV) was also observed following the first dose of BNT162b2 in the 20-39years age group only. A statistically significant association between BNT162b2 vaccination and myo/pericarditis was observed. This association has been confirmed internationally. BNT162b2 was not found to be associated with the other AESIs investigated, except for SOCV following the first dose of BNT162b2 in the 20-39years age group only, providing reassurances around the safety of the vaccine.

Inter-hospital variation in data collection, radiotherapy treatment, and survival in patients with head and neck cancer: A multisite study

Background and purposeInter-hospital inequalities in head and neck cancer (HNC) survival may exist due to variation in radiotherapy treatment-related factors. This study investigated inter-hospital variation in data collection, primary radiotherapy treatment, and survival in HNC patients from an Australian setting. Materials and methodsData collected in oncology information systems (OIS) from seven Australian hospitals was extracted for 3,182 adults treated with curative radiotherapy, with or without surgery or chemotherapy, for primary, non-metastatic squamous cell carcinoma of the head and neck (2000–2017). Death data was sourced from the National Death Index using record linkage. Multivariable Cox regression was used to assess the association between survival and hospital. ResultsInter-hospital variation in data collection, primary radiotherapy dose, and five-year HNC-related death was detected. Completion of eleven fields ranged from 66%-98%. Primary radiotherapy treated Tis-T1N0 glottic and any stage oral cavity and oropharynx cancers received significantly different time-corrected biologically equivalent dose in two gray fractions (EQD2T) by hospital, with observed deviation from Australian radiotherapy guidelines. Increased EQD2T dose was associated with a reduced risk of five-year HNC-related death in all patients and those treated with primary radiotherapy. Hospital, tumour site, and T and N classification were also identified as independent prognostic factors for five-year HNC-related death in all patients treated with radiotherapy. ConclusionUnexplained variation exists in HNC-related death in patients treated at Australian hospitals. Available routinely collected data in OIS are insufficient to explain variation in survival. Innovative data collection, extraction, and classification practices are needed to inform clinical practice.

Ten fraction hypofractionated stereotactic body radiotherapy for the management of ultracentral lung tumors: a retrospective analysis of dosimetry, outcomes, and toxicity

BackgroundThe management of ultracentral thoracic tumors with ablative dose of radiotherapy remains challenging given proximity to critical central structures. We report patient outcomes, toxicity, and dosimetry for ultracentrally located tumors with hypofractionated stereotactic body radiotherapy (hfSBRT).MethodsSeventy-eight individuals (50 initial radiotherapy, 28 re-irradiation) undergoing 10 fraction hfSBRT for ultracentrally located thoracic tumors treated between 2009 and 2020 at a single institution were retrospectively reviewed. Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated. Incidence and grade of treatment related toxicity were evaluated. Dosimetric analysis of treatment plans and critical adjacent OARs was performed.ResultsAt a median follow up time of 13 months, 1- and 3-year OS, PFS, and LC were 89%/63%, 37%/18%, and 84%/65%, respectively. Median dose was 65 Gy (BED10 = 107.25 Gy). Median primary bronchial tree maximum dose (Dmax) was 60 Gy (V50 = 0.96 cc). Median esophageal Dmax was 38 Gy (V40 = 0 cc). Median great vessel Dmax was 68 Gy (V50 = 3.53 cc). The most common ≥ grade 2 adverse event was pneumonitis, in 15 individuals (20%). Grade 3 or higher toxicity was observed in 9 individuals (12%): three cases of grade 3 pneumonitis (two re-irradiation, one initial radiotherapy), one grade 3 esophageal stricture following re-irradiation, two grade 3 endobronchial obstructions both following initial radiotherapy, and three grade 5 hemoptysis events (two re-irradiation, one initial radiotherapy). One hemoptysis event was categorized as “possibly” related to treatment, while the remaining two events were categorized as “unlikely” related to treatment in patients with clear evidence of disease progression.ConclusionshfSBRT to ultracentral lung tumors delivered over 10 fractions is a safe and effective treatment option, with acceptable rates of toxicity and good rates of tumor control.Trial registration: IRB registration number 12573.

Trial of a Novel Radiation Shielding Device to Protect Staff in the Cardiac Catheter Laboratory

Continuous exposure to low-level scattered radiation to staff performing cardiac angiography and intervention is of concern. A novel shielding solution (NSS) (Rampart IC M1128) has the potential to provide greater shielding for staff present at the table-side. This study aimed to investigate the effectiveness of the NSS compared with a traditional shielding solution (TSS) in a randomized controlled trial that enrolled 100 patients who underwent cardiac angiography and/or intervention which were randomized to the NSS or TSS. Baseline patient characteristics and radiation dose data were collected. Staff who were scrubbed at the table-side wore 5 real-time dosimeters on the head, collar, waist, ankle, and under the apron. The median primary operator radiation dose was significantly lower (p<0.001) for all dosimeter locations with the NSS when compared with the TSS, being reduced by 86%, 80.0%, 100%, and 50.0% for the head, collar, waist, and leg respectively. Median under-apron dose was 0.0µSv for both NSS and TSS. Median second operator dose was reduced by 100%, 100%, and 100% for the head, collar, and waist respectively (p<0.001). Median NSS and TSS dose at the ankle and under apron was 0.0µSv. Median scrub nurse dose was reduced by 50% and 100% for the head and collar respectively (p<0.001). Median NSS and TSS dose at the waist, ankle, and under apron was 0.0µSv. In conclusion, the NSS tested in this study demonstrates a significant decrease in radiation dose to operators and scrub nurses when compared with traditional radiation protection measures.

Studies on immunopathological changes induced by commercial IBD live vaccines in poultry birds

Intermediate plus live strain infectious bursal disease virus (IBDV) vaccines are used to control IBDV endemic infections in India. In the present study, immunopathological changes induced by commercial infectious bursal disease live vaccines with different immunization regimes were compared. A total of days old 108 Cobb broiler chicks were randomly divided into five groups with 24 chicks each in groups I, II, III and 18 chicks each in group IV and V. Group I served as control I (no immunization) and group II and III chicks were immunized with a single dose of vaccines 1 and 2 on 17th day of age (DOA), respectively. The group IV and V chicks were immunized with vaccines 1 and 2, respectively with primary dose on 17th DOA followed by booster dose on 24th DOA. Both intermediate plus live vaccines produced gross and histopathological lesions in lymphoid organs (bursa of Fabricius, thymus, spleen and caecal tonsils). Increased CD4 + , CD8 + T cells in affected bursa of Fabricius was evidenced by immunohistochemistry. Further, up-regulation in relative mRNA expression of IFN-γ, IL-1β and IL-6 were observed in bursa of Fabricius of treated birds, with maximum alteration particularly on 14th day post single immunization and 7th day post booster immunization. The findings suggest that single immunization regime on the 17th day of age showed immunization equivalent to booster immunization with lesser lesions, therefore, may be practiced and promoted in the field conditions for the better economic returns and animal welfare.

SOSIALISASI DAN PELAYANAN PEMBERIAN VAKSIN COVID-19 DOSIS 1, 2 DAN BOOSTER UNTUK DEWASA DAN LANSIA

The distribution of the Covid-19 vaccine, both primary and booster doses, is intended to provide artificial immunity against the virus that causes Covid-19, reduce the severity of the Covid-19 virus infection and simultaneously create herd immunity. The purpose of implementing this Community Service activity is to assist the role of the Indonesian government in reducing the impact of the Covid-19 pandemic and breaking the chain of transmission of Covid-19 in Indonesia through the provision of Covid-19 vaccine services. The activity was carried out in collaboration with partners from the Kepolisian Sektor Pamulang which provided health workers and vaccines. The object of this vaccination activity is employees and residents around the Swadharma Pondok Cabe Institute of Technology and Business campus environment, namely 104 persons.

Myocarditis and Pericarditis Post-mRNA COVID-19 Vaccination: Insights from a Pharmacovigilance Perspective.

Concerns remain regarding the rare cardiovascular adverse events, myocarditis and pericarditis (myo/pericarditis), particularly in younger individuals following mRNA COVID-19 vaccination. Our study aimed to comprehensively assess potential safety signals related to these cardiac events following the primary and booster doses, with a specific focus on younger populations, including children as young as 6 months of age. Using the Vaccine Adverse Events Reporting System (VAERS), the United States national passive surveillance system, we conducted a retrospective pharmacovigilance study analyzing spontaneous reports of myo/pericarditis. We employed both frequentist and Bayesian methods and conducted subgroup analyses by age, sex, and vaccine dose. We observed a higher reporting rate of myo/pericarditis following the primary vaccine series, particularly in males and mainly after the second dose. However, booster doses demonstrated a lower number of reported cases, with no significant signals detected after the fourth or fifth doses. In children and young adults, we observed notable age and sex differences in the reporting of myo/pericarditis cases. Males in the 12-17 and 18-24-year-old age groups had the highest number of cases, with significant signals for both males and females after the second dose. We also identified an increased reporting for a spectrum of cardiovascular symptoms such as chest pain and dyspnea, which increased with age, and were reported more frequently than myo/pericarditis. The present study identified signals of myo/pericarditis and related cardiovascular symptoms after mRNA COVID-19 vaccination, especially among children and adolescents. These findings underline the importance for continued vaccine surveillance and the need for further studies to confirm these results and to determine their clinical implications in public health decision-making, especially for younger populations.

Radiographers’ attitudes toward the use of lead contact shielding

IntroductionLead contact shielding has been a crucial component of patient radiation protection since it was first introduced in the early 1900s. Concerns surrounding the hereditary effects of ionising radiation were a driver for using lead shielding. Recently the American Association of Physics in Medicine (AAPM) and the British Institute of Radiology (BIR) have published position papers that suggest that lead contact shielding is no longer needed due to reduced radiation doses for x-ray examinations. This work examines radiographers' opinions on these position papers. MethodsAn online survey with quantitative and qualitative elements was designed to explore knowledge and attitudes toward the BIR and AAPM position papers. The population for this survey was all qualified radiographers. ResultsThe majority (59%) of participants are aware of the AAPM guidance, and 76% are aware of the BIR guidance. Given the changes in the gonad tissue weighting factor, 66% believed additional emphasis should be placed on protecting organs and tissues with higher tissue weighting factors. The vast majority (87%) believed lead shielding is not the primary dose reduction strategy, with 82% agreeing that lead shielding may interfere with the AEC. ConclusionThis study identifies a perception that lead protection may still play a role in patient protection, particularly for children and pregnant patients. However, it is not considered the primary mechanism of protection. More specific guidance and information are needed to incorporate the guidance for radiographers into working practice, improving patient care. Implications for practiceLead shielding remains a tool for radiation protection in particular examinations, however, its role has diminished in clinical practice. RecommendationsAdditional research is required into the number of repeat x-rays associated with the use of lead shielding and the actual dose saving for shielding outside the field of view. Additional education and specific clarification on when to use and not use lead contact shielding is required.

Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study

In a parallel-group, international, phase 3 study (ClinicalTrials.govNCT04762680), we evaluated prototype (D614) and Beta (B.1.351) variant recombinant spike protein booster vaccines with AS03-adjuvant (CoV2 preS dTM-AS03). Adults, previously primed with mRNA (BNT162b2, mRNA-1273), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or protein (CoV2 preS dTM-AS03 [monovalent D614; MV(D614)]) vaccines were enrolled between 29 July 2021 and 22 February 2022. Participants were stratified by age (18-55 and≥56 years) and received one of the following CoV2 preS dTM-AS03 booster formulations: MV(D614) (n=1285), MV(B.1.351) (n=707) or bivalent D614+B.1.351 (BiV; n=625). Unvaccinated adults who tested negative on a SARS-CoV-2 rapid diagnostic test (control group, n=479) received two primary doses, 21 days apart, of MV(D614). Anti-D614G and anti-B.1.351 antibodies were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay 14 days post-booster (day [D]15) in 18-55-year-old BNT162b2-primed participants and compared with those pre-booster (D1) and on D36 in 18-55-year-old controls (primary immunogenicity endpoints). PsVN titers to Omicron BA.1, BA.2 and BA.4/5 subvariants were also evaluated. Safety was evaluated over a 12-month follow-up period. Planned interim analyses are presented up to 14 days post-last vaccination for immunogenicity and over a median duration of 5 months for safety. All three boosters elicited robust anti-D614G or -B.1.351 PsVN responses for mRNA, adenovirus-vectored and protein vaccine-primed groups. Among BNT162b2-primed adults (18-55 years), geometric means of the individual post-booster versus pre-booster titer ratio (95% confidence interval [CI]) were: for MV (D614), 23.37 (18.58-29.38) (anti-D614G); for MV(B.1.351), 35.41 (26.71-46.95) (anti-B.1.351); and for BiV, 14.39 (11.39-18.28) (anti-D614G) and 34.18 (25.84-45.22 (anti-B.1.351). GMT ratios (98.3% CI) versus post-primary vaccination GMTs in controls, were: for MV(D614) booster, 2.16 (1.69; 2.75) [anti-D614G]; for MV(B.1.351), 1.96 (1.54; 2.50) [anti-B.1.351]; and for BiV, 2.34 (1.84; 2.96) [anti-D614G] and 1.39 (1.09; 1.77) [anti-B.1.351]. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 (across priming vaccine subgroups), Omicron BA.1 (BNT162b2-primed participants) and Omicron BA.4/5 (BNT162b2-primed participants and MV D614-primed participants). Similar patterns in antibody responses were observed for participants aged ≥56 years. Reactogenicity tended to be transient and mild-to-moderate severity in all booster groups. No safety concerns were identified. CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. Sanofi and Biomedical Advanced Research and Development Authority (BARDA).

Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters

The SARS-CoV-2 Omicron subvariant BA.5 rapidly spread worldwide and replaced BA.1/BA.2 in many countries, becoming globally dominant. BA.5 has unique amino acid substitutions in the spike protein that both mediate immune escape from neutralizing antibodies produced by immunizations and increase ACE2 receptor binding affinity. In a comprehensive, long-term (up to 9 months post primary vaccination), experimental vaccination study using male Syrian hamsters, we evaluate neutralizing antibody responses and efficacy against BA.5 challenge after primary vaccination with Ad26.COV2.S (Janssen) or BNT162b2 (Pfizer/BioNTech) followed by a homologous or heterologous booster with mRNA-1273 (Moderna) or NVX-CoV2373 (Novavax). Notably, one high or low dose of Ad26.COV2.S provides more durable immunity than two primary doses of BNT162b2, and the NVX-CoV2373 booster provides the strongest augmentation of immunity, reduction in BA.5 viral replication, and disease. Our data demonstrate the immunogenicity and efficacy of different prime/boost vaccine regimens against BA.5 infection in an immune-competent model and provide new insights regarding COVID-19 vaccine strategies.

Hearing loss and tinnitus associated with COVID-19 vaccines: An analysis from the national pharmacovigilance database in Malaysia

Objective: To compare the reporting pattern of hearing loss and tinnitus across different vaccines brands used in Malaysia (BNT162b2, CoronaVac, ChAdOx1, Ad5.CoV2-S and BBIBP-CorV). Methods: This retrospective study included all reports of hearing loss and tinnitus occurring after COVID-19 vaccination that were received in the national pharmacovigilance database, QUEST, from February 24, 2021 through July 31, 2022. Reports given causality consistent or indeterminate were included. Results: There were 21 cases of hearing loss, with overall reporting rate of 0.29 cases per million doses. The rate was similar across BNT162b2, CoronaVac and ChAdOx1. For tinnitus, 35 cases were reported, with the overall reporting rate of 0.49 cases per million doses, and the highest rate was reported for ChAdOx1. For both events, most cases aged 30 to 49 years. No gender disparity was observed. Both events were mainly reported to have occurred after the primary doses, with a median time-to-onset of two days. There were no statistically significant differences in the reporting patterns for both events across BNT162b2, CoronaVac and ChAdOx1 by age group, gender, race, and dose number. Conclusions: Despite the low reporting rates and insufficient evidence to confirm its relationship, hearing loss and tinnitus following vaccinations should not be ignored due to its disabling potential and impact on one's quality of life. Continual reporting is encouraged for better signal characterization in the future.

Methodological quality and recommendations of hemophilia clinical practice guidelines: A scoping review.

Hemophilia clinical practice guidelines (CPGs) play a vital role in guiding healthcare professionals' decisions. However, the quality and recommendations of CPGs for hemophilia may vary. This study aimed to assess the methodological quality of hemophilia CPGs published between 2017 and 2021 and compare their recommendations for prophylaxis using clotting factor concentrate. We conducted a comprehensive search for relevant CPGs in PubMed, TripDatabase, Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) International Guidelines Database, Google Scholar, and Google. We used the AGREE-II instrument to assess the methodological quality of each CPG and compared their recommendations for prophylaxis. Of the 11 CPGs that met the inclusion criteria, 5/11 were developed in upper-middle-income countries, and 6/11 used the GRADE methodology. The primary prophylaxis dose recommendations varied among the CPGs, with 4/11 recommending a low dose, 6/11 recommending an intermediate or high dose, and 1/11 not issuing a recommendation. However, only 2/11 CPGs provided justification for their recommendations on initiation and dose, and no economic evaluations were conducted to support these recommendations. The quality of hemophilia CPGs is not optimal, with inconsistent recommendations for prophylaxis and a lack of justification for these recommendations. To ensure evidence-based and trustworthy recommendations, there is a need for transparency and improvement in the decision-making process of hemophilia CPGs.

Pelvic radiation dose measurement for trauma patients in multifield radiographic examinations: A phantom-based TLD dosimetry study.

Trauma patients often suffer from multiple injuries and require undergoing various radiography which is referred to as multifield radiographic examinations. Protective measures may be ignored for these examinations due to stressful emergency situations or patients' conditions. This study was conducted to evaluate the scattered doses received by the pelvis during different common multifield radiographic examinations with an emphasis on field size adjustment. A whole-body phantom, PBU-50, resembling the body mass, was used to carry out the common examinations for trauma patients (extremities, skull, chest, abdomen, pelvis, femur, and lumbar radiography), using a Pars Pad X-ray machine. To measure the primary entrance skin doses, three calibrated GR 200 thermoluminescence dosimeter (TLD) chips were placed in the central X-ray beam of scanned organs. Three TLDs were also placed on the pelvis symphysis pubis to measure the scattered dose received by the pelvis due to each carried-out radiography for standard and clinically used field sizes. A Harshaw 3500 TLD Reader was used to read the chips. TLD readouts (nano-Coulomb) were converted to dose (milli Gray [mGy]) using the predefined calibration curve. The scattered doses to the pelvis due to scanning a single organ differed from 0.80 to 1.70, and 0.82 to 4.09 mGy for standard and clinically used field sizes, respectively. The scattered doses to the pelvis in multifield examinations varied from 0.80 to 8.43 and 0.82 to 13.6 mGy for standard and clinically used field sizes, respectively, depending on the number of scanned organs and their distances from the pelvis. Multiple and repeated radiographs combined with insufficient protective measures can increase the patient's dose. The findings indicate that the scattered doses received by the pelvis can exceed the reference values in multifield radiography, especially if the radiation field is not restricted properly to the scanned organ.

Immune Response Kinetics Following a Third Heterologous BNT162b2 Booster Dose After Primary 2-Dose ChAdOx1 Vaccination in Relation to Omicron Breakthrough Infection: A Prospective Nationwide Cohort Study in South Korea.

Immune responses to each vaccine must be investigated to establish effective vaccination strategies for the ongoing coronavirus disease (COVID-19) pandemic. We investigated the long-term kinetics of immune responses after heterologous booster vaccination in relation to Omicron breakthrough infection (BI). Our study included 373 healthcare workers who received primary ChAdOx1 vaccine doses and a third BNT162b2 vaccine dose. BIs that occurred after the third vaccine were investigated. Blood specimens were collected before and 3 months after the booster dose from participants without BI and 1, 4, and 6 months after BI from participants who experienced BI. Spike-specific binding and neutralizing antibody levels against the wild-type virus, Omicron BA.1, and Omicron BA.5, as well as cellular responses, were analyzed. A total of 346 participants (82 in the no BI group; 192 in the BI group during the BA.1/BA.2 period; 72 in the BI group during the BA.5 period) were included in the analysis. Participants without BI exhibited the highest binding and neutralizing antibody concentrations and greatest cellular response 1 month after the third vaccination, which reached a nadir by the ninth month. Antibody and cellular responses in participants who experienced BI substantially increased postinfection. Neutralizing antibody titers in individuals who experienced BI during the BA.1/BA.2 period showed more robust increase against wild-type virus than against BA.1 and BA.5. Our findings provide evidence of antigenic imprinting in participants who received a heterologous booster vaccination, thereby serving as a foundation for further studies on the impact of BIs on immune responses.

Estimating the Cost-Effectiveness of Switching to Higher-Valency Pediatric Pneumococcal Conjugate Vaccines in the United Kingdom.

Currently, the 13-valent pneumococcal conjugate vaccine (PCV13) is administered under a 1+1 (1 primary dose) pediatric schedule in the United Kingdom (UK). Higher-valency PCVs, 15-valent PCV (PCV15), or 20-valent PCV (PCV20) might be considered to expand serotype coverage. We evaluated the cost-effectiveness of PCV20 or PCV15 using either a 2+1 (2 primary doses) or 1+1 schedule for pediatric immunization in the UK. Using a dynamic transmission model, we simulated future disease incidence and costs under PCV13 1+1, PCV20 2+1, PCV20 1+1, PCV15 2+1, and PCV15 1+1 schedules from the UK National Health Service perspective. We prospectively estimated disease cases, direct costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Scenario analyses were performed to estimate the impact of model assumptions and parameter uncertainty. Over a five-year period, PCV20 2+1 averted the most disease cases and gained the most additional QALYs. PCV20 2+1 and 1+1 were dominant (cost-saving and more QALYs gained) compared with PCV15 (2+1 or 1+1) and PCV13 1+1. PCV20 2+1 was cost-effective (GBP 8110/QALY) compared with PCV20 1+1. PCV20 was found cost-saving compared with PCV13 1+1, and PCV20 2+1 was cost-effective compared with PCV20 1+1. Policymakers should consider the reduction in disease cases with PCV20, which may offset vaccination costs.

Preliminary Population Exposure to Indoor Radon and Thoron in Dhaka City, Bangladesh

Radon, an element of natural radiation, is considered one of the leading causes of lung cancer worldwide. In Bangladesh, radon has been clarified as a foremost source of radiation exposure. Potential natural-radiation-induced elevated cancer risks were estimated in Bangladesh previously for the population. In this survey, as a very preliminary study in the country, comparative indoor radon (222Rn, Rn) and thoron (220Rn, Tn) concentration/population exposure was determined for the multistoried dwellings of south-western areas of Dhaka city. RADUET was used to assess annual Rn and Tn concentrations in determining the primary inhalation dose for the population. The annual effective dose of Rn and Tn was evaluated in this study for dwellings at 0.3 mSvy−1, constituting a Tn dose contribution of an average of 40% with a dwelling-based wide range of 10–96%. Thus, Tn should not be neglected for Bangladesh while estimating radiological inhalation dose from the indoor environment. Again, the equilibrium factors, F of Rn and Tn, were determined by short-term measurement at averages of 0.6 and 0.02, respectively. Furthermore, using questionnaire estimation by principal component analysis, PCA following the dwelling characteristics, human lifestyles, and estimated long-term indoor Rn and Tn concentrations, this paper discussed indoor atmospheric/Rn factors for the investigated multistoried dwellings in Dhaka city.

Characterization of immune responses to two and three doses of the adenoviral vectored vaccine ChAdOx1 nCov-19 and the whole virion inactivated vaccine BBV152 in a mix-and-match study in India

Infections with SARS-CoV-2 variants and declining immunity after primary vaccination, encouraged the use of booster doses. Some countries changed their immunization programmes to boost with vaccines different from the ones in their original schedule, based on results from immunogenicity and effectiveness studies. This study reports immunological analysis of samples collected in a phase 4 randomized trial, where participants who had previously received two primary doses of ChAdOx1 nCov-19 (ChAd) or inactivated BBV152 vaccine were randomized to receive either ChAd or BBV152 booster and further categorized as: Group 1 (two primary doses of ChAd - ChAd booster), Group 2 (two primary doses of ChAd - BBV152 booster), Group 3 (two primary doses of BBV152 - ChAd booster), and Group 4 (two primary doses of BBV152 - BBV152 booster). SARS-CoV-2 specific cellular and humoral responses at day 0 (pre-boost samples 12–36 weeks after the second primary dose), and at day 28 post booster, were measured in a subset of participants (ChAd recipients, n = 37 and BBV152 recipients, n = 36). Additionally, on day180 post-booster humoral responses were assessed for the entire cohort (N = 378). Primary vaccination with 2 doses of BBV152 generated higher memory-B cells (median% 0.41 vs 0.35) and cytokine producing CD8-Tcells (median% 0.09 vs 0.04) while lower anti-spike IgG levels (medianAU/ml: 12,433 vs 27,074) as compared to ChAd. Irrespective of the primary vaccine received, ChAd boosted individuals generated higher memory-B cell frequencies and anti-spike IgG levels as compared to BBV152 booster. The percentage ACE-2 inhibition against Omicron and its sub-variants was higher in Group 3 (median > 60 %) as compared to other groups (median < 25 %). At day180 post booster the hierarchy of the antibody amounts was Group 1 ∼ Group 2 ∼ Group 3 > Group 4.Sustained humoral and robust cellular immune response to SARS-CoV-2 can be obtained with ChAd booster irrespective of the primary vaccination regimen. The trial is registered with ISRTCN (CTRI/2021/08/035648).

Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033)

BackgroundThis phase III study evaluated safety, tolerability, and immunogenicity of V114 (15-valent pneumococcal conjugate vaccine) in Japanese infants. V114 contains all 13 serotypes in PCV13 plus additional serotypes 22F and 33F. MethodsHealthy Japanese infants were randomized to receive three primary doses of V114 or PCV13 (dose 1 at 2–6 months of age; doses 2 and 3 ≥ 27 days after prior dose), plus a toddler dose at 12–15 months of age. Adverse events (AEs) were collected on Days 1–14 following each vaccination. Serotype-specific anti-pneumococcal immunoglobulin G (IgG) was measured 30 days post-dose 3, pre-dose 4, and 30 days post-dose 4. Primary objectives included non-inferiority of V114 to PCV13 for the 13 shared serotypes based on serotype-specific IgG response rates (IgG ≥ 0.35 μg/mL) and geometric mean concentration (GMC) ratios, and for serotypes 22F and 33F based on IgG response rates and compared with the lowest response of any serotype in the PCV13 group, at 30 days post-dose 3. ResultsOverall, 694 infants were randomized to V114 (n = 347) or PCV13 (n = 347). Proportions of participants with solicited and serious AEs were comparable between vaccination groups. V114 met non-inferiority criteria for all 13shared serotypes, based on difference in proportion of responders (lower bound of two-sided 95 % confidence interval [CI] > −10.0) and IgG GMC ratios (V114/PCV13, lower bound of two-sided 95 % CI > 0.5) at 30 days post-dose 3. The non-inferiority criterion based on IgG response rates was met for serotype 22F, but narrowly missed for serotype 33F (90.9 %, lower bound of two-sided 95 % CI −10.6). ConclusionIn Japanese infants, a four-dose series of V114 was generally well tolerated. Compared with PCV13, V114 provided non-inferior immune responses to the 13 shared serotypes and higher immune responses to serotype 22F and 33F post-primary series.Trial registration:ClinicalTrials.gov: NCT04384107; EudraCT 2019-003644-68.

Evaluation of potential adverse events following COVID-19 mRNA vaccination among adults aged 65 years and older: Two self-controlled studies in the U.S.

BackgroundOur near-real-time safety monitoring of 16 adverse events (AEs) following COVID-19 mRNA vaccination identified potential elevation in risk for six AEs following primary series and monovalent booster dose administration. The crude association with AEs does not imply causality. Accordingly, we conducted robust evaluation of potential associations. MethodsWe conducted two self-controlled case series studies of COVID-19 mRNA vaccines (BNT162b2 and mRNA-1273) in U.S. Medicare beneficiaries aged ≥ 65 years. Adjusted incidence rate ratio (IRRs) and 95 % confidence intervals (CIs) were estimated following primary series doses for acute myocardial infarction (AMI), pulmonary embolism (PE), immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC); and following monovalent booster doses for AMI, PE, ITP, Bell’s Palsy (BP) and Myocarditis/Pericarditis (Myo/Peri). ResultsThe primary series study included 3,360,981 individuals who received 6,388,542 primary series doses; the booster study included 6,156,100 individuals with one monovalent booster dose. The AMI IRR following BNT162b2 primary series and booster was 1.04 (95 % CI: 0.91 to 1.18) and 1.06 (95 % CI: 1.003 to 1.12), respectively; for mRNA-1273 primary series and booster, 1.01 (95 % CI: 0.82 to 1.26) and 1.05 (95 % CI: 0.998 to 1.11), respectively. The hospital inpatient PE IRR following BNT162b2 primary series and booster was 1.19 (95 % CI: 1.03 to 1.38) and 0.86 (95 % CI: 0.78 to 0.95), respectively; for mRNA-1273 primary series and booster, 1.15 (95 % CI: 0.94 to 1.41) and 0.87 (95 % CI: 0.79 to 0.96), respectively. The studies’ results do not support that exposure to COVID-19 mRNA vaccines elevate the risk of ITP, DIC, Myo/Peri, and BP. ConclusionWe did not find an increased risk for AMI, ITP, DIC, BP, and Myo/Peri and there was not consistent evidence for PE after exposure to COVID-19 mRNA primary series or monovalent booster vaccines. These results support the favorable safety profile of COVID-19 mRNA vaccines administered in the U.S. elderly population.