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The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were randomly assigned to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 μg (15 μg of BNT162b2 + 15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2 + 30 μg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT ] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 μg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. A total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 μg), with NT geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 μg) were also noninferior to BNT162b2 (30 μg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain, with NT GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-μg bivalent BA.1 than with 30-μg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 μg). Adverse events were more common in the 30-μg monovalent-BA.1 (8.5%) and 60-μg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). The candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 μg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.).

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of an ongoing, open-label, phase 2/3 study of monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy participants ≥12 years old (N = 412 (12–17 years, N = 30; 18–55 years, N = 174; >55 years, N = 208)) who previously received ≥3 doses of a US-authorized mRNA vaccine, the most recent being an Omicron BA.4/BA.5-adapted bivalent vaccine ≥150 days before study vaccination, were vaccinated. Serum 50% neutralizing titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 were measured 7 days and 1 month after vaccination in a subset of ≥18-year-olds (N = 40) who were positive for SARS-CoV-2 at baseline. Seven-day immunogenicity was also evaluated in a matched group who received bivalent BA.4/BA.5-adapted BNT162b2 in a previous study (ClinicalTrials.gov Identifier: NCT05472038). There were no new safety signals; local reactions and systemic events were mostly mild to moderate in severity, adverse events were infrequent, and none led to study withdrawal. The XBB.1.5-adapted BNT162b2 induced numerically higher titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 than BA.4/BA.5-adapted BNT162b2 at 7 days and robust neutralizing responses to all three sublineages at 1 month. These data support a favorable benefit-risk profile of XBB.1.5-adapted BNT162b2 30 μg. ClinicalTrials.gov Identifier: NCT05997290

Mobile health (mHealth) wearable devices are increasingly being adopted by individuals to help manage and monitor physiological signals. However, the current state of wearables does not consider the needs of racially minoritized low-socioeconomic status (SES) communities regarding usability, accessibility, and price. This is a critical issue that necessitates immediate attention and resolution. This study's aims were 3-fold, to (1) understand how members of minoritized low-SES communities perceive current mHealth wearable devices, (2) identify the barriers and facilitators toward adoption, and (3) articulate design requirements for future wearable devices to enable equitable access for these communities. We performed semistructured interviews with low-SES Hispanic or Latine adults (N=19) from 2 metropolitan cities in the Midwest and West Coast of the United States. Participants were asked questions about how they perceive wearables, what are the current benefits and barriers toward use, and what features they would like to see in future wearable devices. Common themes were identified and analyzed through an exploratory qualitative approach. Through qualitative analysis, we identified 4 main themes. Participants' perceptions of wearable devices were strongly influenced by their COVID-19 experiences. Hence, the first theme was related to the impact of COVID-19 on the community, and how this resulted in a significant increase in interest in wearables. The second theme highlights the challenges faced in obtaining adequate health resources and how this further motivated participants' interest in health wearables. The third theme focuses on a general distrust in health care infrastructure and systems and how these challenges are motivating a need for wearables. Lastly, participants emphasized the pressing need for community-driven design of wearable technologies. The findings from this study reveal that participants from underserved communities are showing emerging interest in using health wearables due to the COVID-19 pandemic and health care access issues. Yet, the needs of these individuals have been excluded from the design and development of current devices.

Introduction Vaccination is a critical tool for preventing coronavirus disease 2019 (COVID-19) and influenza illnesses. Coadministration of the COVID-19 vaccine, BNT162b2, with seasonal inactivated influenza vaccine (SIIV) can provide substantial benefits, including streamlining vaccine delivery. Methods In this phase 3 study, healthy 18- to 64-year-olds who had received three previous doses of BNT162b2 were randomized (1:1) to the coadministration group (month 0, BNT162b2 + SIIV; month 1, placebo) or the separate-administration group (month 0, placebo + SIIV; month 1, BNT162b2). The primary immunogenicity objective was to demonstrate that the immune responses elicited by BNT162b2 and SIIV [measured by full-length S-binding immunoglobulin G (IgG) levels and strain-specific hemagglutination inhibition assay (HAI) titers against four influenza strains 1 month post-vaccination, respectively] when coadministered were noninferior to those elicited by either vaccine administered alone, based on a prespecified 1.5-fold noninferiority margin [lower bound 95% CI for geometric mean ratio (GMR) > 0.67]. Reactogenicity and adverse event (AE) rates were evaluated. Results Randomized participants who received study vaccination ( N  = 1128; coadministration group, n  = 564; separate-administration group, n  = 564) had a median age of 39 years. Model-adjusted GMRs for coadministration to separate administration were 0.83 (95% CI 0.77, 0.89) for full-length S-binding IgG levels and 0.89–1.00 (lower bound of all 95% CIs > 0.67) for the four influenza strain-specific HAI titers, with all endpoints achieving the prespecified noninferiority criterion. Reactogenicity events were mostly mild or moderate when BNT162b2 was coadministered with SIIV. Serious AEs were reported in < 1% of participants within 1 month after any vaccination; none were considered vaccine-related. Conclusions BNT162b2 coadministered with SIIV elicited immune responses that were noninferior to those elicited by BNT162b2 alone and SIIV alone, and BNT162b2 had an acceptable safety profile when coadministered with SIIV. The results of this study support the coadministration of BNT162b2 and SIIV in adults. Trial Registration ClinicalTrials.gov registration: NCT05310084.

In an extension of the pivotal randomized trial showing vaccine efficacy, approximately 10,000 adults who had received two doses of BNT162b2 were assigned to receive a third dose or placebo. Local reactions were common but mild and transient. During a median follow-up of 2.5 months, SARS-CoV-2 was identified in 6 participants in the vaccine group and in 123 in the placebo group, for a vaccine efficacy of 95.3%.

Three 3-μg doses of the BNT162b2 vaccine were found to be immunogenic in children younger than 5 years of age and were associated with local reactions and systemic events that were similar to those seen in older children.

•We show BNT162b2 vaccine ph or phase 3 data from participants with baseline history of past/active neoplasm.•Efficacy and safety were evaluated through up to 6 months of follow-up post-BNT162b2 dose 2.•BNT162b2 has similar efficacy in those with history of past/active neoplasm as overall population.•BNT162b2 has favorable safety profile in these participants, similar to overall study population.•Results inform real-world use of BNT162b2 during the pandemic and future trials in cancer patients. Individuals with an underlying malignancy have high risk of poor COVID-19 outcomes. In clinical trials, COVID-19 vaccines were safe and efficacious against infection, hospitalization, and death, but most trials excluded participants with cancer. We report results from participants with a history of past or active neoplasm (malignant or benign/unknown) and up to 6 months’ follow-up post-dose 2 from the placebo-controlled, observer-blinded trial of the 2-dose BNT162b2 mRNA COVID-19 vaccine. Between July 2020–January 2021, 46,429 participants aged ≥ 12 years were randomized at 152 sites in 6 countries. Healthy participants with pre-existing stable neoplasm could participate; those receiving immunosuppressive therapy were excluded. Data are reported for participants, aged ≥ 16 years for safety and ≥ 12 years for efficacy, who had any history of neoplasm at baseline (data cut-off: March 13, 2021). Adverse-event (AE) data are controlled for follow-up time before unblinding and reported as incidence rates (IRs) per 100 person-years follow-up. At baseline, 3813 participants had a history of neoplasm; most common malignancies were breast (n = 460), prostate (n = 362), and melanoma (n = 223). Four BNT162b2 and 71 placebo recipients developed COVID-19 from 7 days post-dose 2; vaccine efficacy was 94.4% (95% CI: 85.2, 98.5) after up to 6 months’ follow-up post-dose 2. This compares favorably with vaccine efficacy of 91.1% in the overall trial population after the same follow-up. AEs were reported at IRs of 95.4(BNT162b2) and 48.3 (placebo) per 100 person-years. Most common AEs were reactogenicity events (injection-site pain, fatigue, pyrexia). Three BNT162b2 and 1 placebo recipients withdrew because of vaccine-related AEs. No vaccine-related deaths were reported. In participants with past or active neoplasms, BNT162b2 vaccine has a similar efficacy and safety profile as in the overall trial population. These results can inform BNT162b2 use during the COVID-19 pandemic and future trials in participants with cancer. Clinical trial number: NCT04368728.

Manipulating the signaling environment is an effective approach to alter cellular states for broad-ranging applications, from engineering tissues to treating diseases. Such manipulation requires knowing the signaling states and histories of the cells , for which high-throughput discovery methods are lacking. Here, we present an integrated experimental-computational framework that learns signaling response signatures from a high-throughput perturbation atlas and infers combinatorial signaling activities in cell types with high accuracy and temporal resolution. Specifically, we generated signaling perturbation atlas across diverse cell types/states through multiplexed sequential combinatorial screens on human pluripotent stem cells. Using the atlas to train IRIS, a neural network-based model, and predicting on mouse embryo scRNAseq atlas, we discovered global features of combinatorial signaling code usage over time, identified biologically meaningful heterogeneity of signaling states within each cell type, and reconstructed signaling histories along diverse cell lineages. We further demonstrated that IRIS greatly accelerates the optimization of stem cell differentiation protocols by drastically reducing the combinatorial space that needs to be tested. This framework leads to the revelation that different cell types share robust signal response signatures, and provides a scalable solution for mapping complex signaling interactions to guide targeted interventions.

This study investigates the vulnerabilities of Solstice Pods, wireless collaboration devices often used in academic environments, focusing on universities with publicly exposed devices. We analyzed 22 universities, each with 10 or fewer Solstice Pods exposed on Censys.io, a platform for identifying publicly exposed devices. This subset was selected to emphasize vulnerabilities in smaller, publicly exposed systems, without excluding large institutions that may have only a few devices exposed. Our research centers on unauthorized access to device configuration pages and the retrieval of live session keys, which are critical for screen sharing. From 81 exposed Solstice Pods, we manually examined several IP addresses and found that critical configurations, including screen-key disabling, password changes, and session key retrieval, were accessible in some cases. To scale testing, we developed the Solstice Pod Access Retrieval Key (SPARK), a Python tool using SSL/TLS requests to interact with the devices' configuration pages. The SPARK tool successfully generated live session keys in 13 instances across 9 universities, while 68 attempts failed. Statistical analysis revealed that self-signed certificates (issued by Mersive, the Solstice Pod vendor) significantly reduced vulnerability to the SPARK tool, with a success rate of 8.33% for devices using self-signed certificates, compared to 63.89% for those with non-self-signed certificates. To assess the statistical significance of this difference, Chi-square and Fisher's exact tests were performed, yielding p-values of 0.0464 and 0.0231, respectively. Additionally, a proportions test showed a highly significant result with a p-value of 0.00077. This study underscores the risks of publicly exposed Solstice Pods and highlights the real-world consequences of these vulnerabilities. If exploited, these vulnerabilities could lead to unauthorized access to sensitive data, disruption of university operations, and compromise of ongoing academic collaborations. The findings call for stronger security measures, particularly the use of self-signed certificates, to reduce vulnerabilities and protect sensitive information in these devices.