Safety and durability of mRNA-1273-induced SARS-CoV-2 immune responses in adolescents: results from the phase 2/3 TeenCOVE trial.

Background: Longitudinal changes in vaccination-induced immune response remain inadequately characterized in adolescents. We present long-term safety, immunogenicity, and COVID-19 incidence following a 2-dose mRNA-1273 100-µg primary series, and immunogenicity following a single dose of mRNA-1273 50 µg in vaccine-naïve adolescents. Methods: TeenCOVE (NCT04649151) Part 1 randomized adolescents (12-17 years) to 2-dose mRNA-1273 100 µg (n = 2490) or placebo (n = 1243) 28 days apart. Subsequently, placebo recipients (n = 91) could receive open-label mRNA-1273. Primary objectives included prespecified adverse events through 12 months; secondary objectives were COVID-19 incidence and neutralizing and spike-binding antibodies (nAbs/bAbs) against SARS-CoV-2 (ancestral/variants) through 12 months (study period: December 2020-January 2022). In Part 2, vaccine-naïve adolescents (n = 52) received up to 2 doses of mRNA-1273 50 µg; interim analysis included Day 28 (D28) nAbs post-injection 1 in SARS-CoV-2-baseline-positive participants (serologic/virologic evidence of prior infection). Findings: In SARS-CoV-2-baseline-negative adolescents (N = 369), mRNA-1273 induced robust nAb responses versus baseline (geometric mean concentration [GMC] = 11; 95% CI, 11-12) at D28 (1868 [1759-1985]), 6 months (625 [583-670]) and 12 months (550 [490-618]) post-injection 2. Similar bAb responses were observed to alpha/beta/delta/gamma variants; nAb/bAb responses were similar in SARS-CoV-2-baseline-positive adolescents. The 2-dose mRNA-1273 100-µg primary series was generally well-tolerated; one case of nonserious, moderate, probable acute myocarditis resolved by 8 days from symptom onset. A single dose of mRNA-1273 50 µg in SARS-CoV-2-baseline-positive adolescents induced higher D28 nAb GMCs against ancestral SARS-CoV-2 than 2-dose mRNA-1273 100 µg in young adults (geometric mean ratio = 4.322 [3.274-5.707]). Interpretation: The overall risk-benefit profile of mRNA-1273 remains favorable in adolescents, with durable 12-month immune responses against SARS-CoV-2 (ancestral/variants). A single mRNA-1273 50-µg injection in vaccine-naïve adolescents elicited robust immune responses against SARS-CoV-2. Funding: This project has been funded in whole or in part with federal funds by the Department of Health and Human Services, United States; Administration for Strategic Preparedness and Response, United States; Biomedical Advanced Research and Development Authority, United States, under Contract No. 75A50120C00034. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Department of Health and Human Services or its components.

Safety and Immunogenicity of an mRNA-1273 Booster in Children.

BACKGROUND: A 2-dose mRNA-1273 primary series in children aged 6 months-5 years (25-µg) and 6-11 years (50-µg) had an acceptable safety profile and was immunogenic in the phase 2/3 KidCOVE study. We present data from KidCOVE participants who received an mRNA-1273 booster dose. METHODS: An mRNA-1273 booster dose (10-µg for children aged 6 months-5 years; 25-µg for children aged 6-11 years; age groups based on participant age at enrollment) was administered ≥6 months after primary series completion. The primary safety objective was the safety and reactogenicity of an mRNA-1273 booster dose. The primary immunogenicity objective was to infer efficacy of an mRNA-1273 booster dose by establishing noninferiority of neutralizing antibody (nAb) responses after a booster in children compared with nAb responses observed after the mRNA-1273 primary series in young adults (18-25 years) from the pivotal efficacy study. Data were collected from March 2022 to June 2023. RESULTS: Overall, 153 (6 months-5 years) and 2519 (6-11 years) participants received an mRNA-1273 booster dose (median age at receipt of booster: 2 and 10 years, respectively). The booster dose safety profile was generally consistent with that of the primary series in children; no new safety concerns were identified. An mRNA-1273 booster dose elicited robust nAb responses against ancestral SARS-CoV-2 among children and met prespecified noninferiority success criteria when compared with responses observed after the primary series in young adults. CONCLUSIONS: Safety and immunogenicity data support administration of a mRNA-1273 booster dose in children aged 6 months to 11 years. CLINICAL TRIALS REGISTRATION: NCT04796896.

Changes in Screening Test Volume in the National Breast and Cervical Cancer Early Detection Program during the COVID-19 Pandemic, 2020-2022.

INTRODUCTION: The National Breast and Cervical Cancer Early Detection Program (NBCCEDP) observed significant declines in screening volume early in the COVID-19 pandemic, January-June 2020, with variation by race/ethnicity and geography. We aimed to determine how screening in the NBCCEDP recovered from these early declines as it is important for monitoring the long-term impact on women served by the program. METHODS: Extending the previous analyses, we compared monthly breast (BC) and cervical cancer (CVC) screening volume in the NBCCEDP during 2020-2022, to five-year, pre-COVID-19 pandemic averages (2015-2019), and calculated percent change. Results were stratified by race/ethnicity and rurality groups. We employed multiple one-way ANOVA tests, which included multiple comparisons, to test for significant differences between groups. RESULTS: By December 2022, NBCCEDP breast and cervical cancer screening volumes had not fully recovered to pre-COVID-19 5-year averages, and recovery in breast cancer screening volume was slower than that of cervical cancer. Both BC and CVC screening among women in metro areas showed the smallest average monthly deficits (-8.8% BC and -4.9% CVC) compared to monthly pre-COVID-19 pandemic 5-year averages, and screening among women in rural areas showed the greatest deficits (-37.3% BC and -26.7% CVC). BC and CVC screening among Hispanic women showed the greatest improvements compared to the pre-COVID-19 averages (8.2% BC and 9.5% CVC), and cervical cancer screening among non-Hispanic Asian and Pacific Islander women showed the greatest deficits (-41.4% CVC). CONCLUSION: For increased intervention efforts, NBCCEDP recipients can focus on populations demonstrating greatest deficits in screening volume.

Hepatic stearoyl-CoA desaturase-1 deficiency induces fibrosis and hepatocellular carcinoma-related gene activation under a high carbohydrate low fat diet.

Stearoyl-CoA desaturase-1 (SCD1) is a pivotal enzyme in lipogenesis, which catalyzes the synthesis of monounsaturated fatty acids (MUFA) from saturated fatty acids, whose ablation downregulates lipid synthesis, preventing steatosis and obesity. Yet deletion of SCD1 promotes hepatic inflammation and endoplasmic reticulum stress, raising the question of whether hepatic SCD1 deficiency promotes further liver damage, including fibrosis. To delineate whether SCD1 deficiency predisposes the liver to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), we employed in vivo SCD1 deficient global and liver-specific mouse models fed a high carbohydrate low-fat diet and in vitro established AML12 mouse cells. The absence of liver SCD1 remarkably increased the saturation of liver lipid species, as indicated by lipidomic analysis, and led to hepatic fibrosis. Consistently, SCD1 deficiency promoted hepatic gene expression related to fibrosis, cirrhosis, and HCC. Deletion of SCD1 increased the circulating levels of Osteopontin, known to be increased in fibrosis, and alpha-fetoprotein, often used as an early marker and a prognostic marker for patients with HCC. De novo lipogenesis or dietary supplementation of oleate, an SCD1-generated MUFA, restored the gene expression related to fibrosis, cirrhosis, and HCC. Although SCD1 deficient mice are protected against obesity and fatty liver, our results show that MUFA deprivation results in liver injury, including fibrosis, thus providing novel insights between MUFA insufficiency and pathways leading to fibrosis, cirrhosis, and HCC under lean non-steatotic conditions.

Humoral Immunogenicity of mRNA-1345 RSV Vaccine in Older Adults.

BACKGROUND: The mRNA-1345 vaccine demonstrated efficacy against RSV disease with acceptable safety in adults ≥60 years in the ConquerRSV trial. Here, humoral immunogenicity results from the trial are presented. METHODS: This phase 2/3 trial randomly assigned adults (≥60 years) to mRNA-1345 50-µg encoding prefusion F (preF) glycoprotein (n = 17,793) vaccine or placebo (n = 17,748). RSV-A and RSV-B neutralizing antibody (nAb) and preF binding antibody (bAb) levels at baseline and day 29 post-vaccination were assessed in a per-protocol immunogenicity subset ([PPIS]; mRNA-1345, n = 1515; placebo, n = 333). RESULTS: Day 29 nAb geometric mean titers (GMTs) increased 8.4-fold against RSV-A and 5.1-fold against RSV-B from baseline. Seroresponses (4-fold rise from baseline) in the mRNA-1345 groups were 74.2% and 56.5% for RSV-A and RSV-B, respectively. Baseline GMTs were lower among participants who met the seroresponse criteria than those who did not. mRNA-1345 induced preF bAbs at day 29, with a pattern similar to nAbs. Day 29 antibody responses across demographic and risk subgroups were generally consistent with the overall PPIS. CONCLUSION: mRNA-1345 enhanced RSV-A and RSV-B nAbs and preF bAbs in adults (≥60 years) across various subgroups, including those at risk for severe disease, consistent with its demonstrated efficacy in the prevention of RSV disease.

Vital Signs: Mammography Use and Association with Social Determinants of Health and Health-Related Social Needs Among Women - United States, 2022.

Introduction: Approximately 40,000 U.S. women die from breast cancer each year. Mammography is recommended to screen for breast cancer and reduce breast cancer mortality. Adverse social determinants of heath (SDOH) and health-related social needs (HRSNs) (e.g., lack of transportation and social isolation) can be barriers to getting mammograms. Methods: Data from the 2022 Behavioral Risk Factor Surveillance System were analyzed to estimate the prevalence of mammography use within the previous 2 years among women aged 40-74 years by jurisdiction, age group, and sociodemographic factors. The association between mammography use and measures of SDOH and HRSNs was assessed for jurisdictions that administered the Social Determinants and Health Equity module. Results: Among women aged 50-74 years, state-level mammography use ranged from 64.0% to 85.5%. Having health insurance and a personal health care provider were associated with having had a mammogram within the previous 2 years. Among women aged 50-74 years, mammography prevalence was 83.2% for those with no adverse SDOH and HRSNs and 65.7% for those with three or more adverse SDOH and HRSNs. Life dissatisfaction, feeling socially isolated, experiencing lost or reduced hours of employment, receiving food stamps, lacking reliable transportation, and reporting cost as a barrier for access to care were all strongly associated with not having had a mammogram within the previous 2 years. Conclusions and Implications for Public Health Practice: Identifying specific adverse SDOH and HRSNs that women experience and coordinating activities among health care providers, social services, community organizations, and public health programs to provide services that help address these needs might increase mammography use and ultimately decrease breast cancer deaths.

Breast and cervical cancer programs' success in maintaining screening during periods of high COVID-19: A qualitative multi-case study analysis.

Objective: During the first year of the COVID-19 pandemic, most of the Centers for Disease Control and Prevention (CDC)'s National Breast and Cervical Cancer Early Detection Program (NBCCEDP) funded programs (recipients) experienced significant declines in breast and cervical cancer screening volume. However, 6 recipients maintained breast and/or cervical cancer screening volume during July-December 2020 despite their states' high COVID-19 test percent positivity. We led a qualitative multi-case study to explore these recipients' actions that may have contributed to screening volume maintenance. Methods: We conducted 22 key informant interviews with recipients, screening provider sites, and partner organizations. Interviews explored organizational and operational changes; screening barriers; actions taken to help maintain screening volume; and support for provider sites to continue screening. We documented contextual factors that may have influenced these actions, including program structures; clinic capacity; and state COVID-19 policies. Results: Thematic analysis revealed crosscutting themes at the recipient, provider site, and partner levels. Recipients made changes to administrative processes to reduce burden on provider sites and delivered tailored technical assistance to support safe screening. Provider sites modified clinic protocols to increase patient safety, enhanced patient reminders for upcoming appointments, and increased patient education on the importance of timely screening during the pandemic. Partners worked with provider sites to identify and reduce patients' structural barriers to screening. Conclusion: Study findings provide lessons learned to inform emergency preparedness-focused planning and operations, as well as routine operations for NBCCEDP recipient programs, other cancer screening initiatives, primary care clinics, and chronic disease prevention programs.

Interim safety and immunogenicity of COVID-19 omicron BA.1 variant-containing vaccine in children in the USA: an open-label non-randomised phase 3 trial.

BACKGROUND: Variant-containing mRNA vaccines for COVID-19 to broaden protection against SARS-CoV-2 variants are recommended based on findings in adults. We report interim safety and immunogenicity of an omicron BA.1 variant-containing (mRNA-1273.214) primary vaccination series and booster dose in paediatric populations. METHODS: This open-label, two-part, non-randomised phase 3 trial enrolled participants aged 6 months to 5 years at 24 US study sites. Eligible participants were generally healthy or had stable chronic conditions, without known SARS-CoV-2 infection in the previous 90 days. Individuals who were acutely ill or febrile 1 day before or at the screening visit or those who previously received other COVID-19 vaccines (except mRNA-1273 for part 2) were excluded. In part 1, SARS-CoV-2-vaccine-naive participants received two-dose mRNA-1273.214 (25 µg; omicron BA.1 and ancestral Wuhan-Hu-1 mRNA) primary series. In part 2, participants who previously completed the two-dose mRNA-1273 (25 µg) primary series in KidCOVE (NCT04796896) received a mRNA-1273.214 (10 µg) booster dose. Primary study outcomes were safety and reactogenicity of the mRNA-1273.214 primary series (part 1) or booster dose (part 2) as well as the inferred effectiveness of mRNA-1273.214 based on immune responses against ancestral SARS-CoV-2 (D614G) and omicron BA.1 variant at 28 days post-primary series (part 1) or post-booster dose (part 2). The safety set included participants who received at least one dose of the study vaccine; the immunogenicity set included those who provided immunogenicity samples. Interim safety and immunogenicity are summarised in this analysis as of the data cutoff date (Dec 5, 2022). This trial is registered with ClinicalTrials.gov, NCT05436834. FINDINGS: Between June 21, 2022, and Dec 5, 2022, 179 participants received one or more doses of mRNA-1273.214 primary series (part 1) and 539 received a mRNA-1273.214 booster dose (part 2). The safety profile within 28 days after either dose of the mRNA-1273.214 primary series and the booster dose was consistent with that of the mRNA-1273 primary series in this age group, with no new safety concerns or vaccine-related serious adverse events observed. At 28 days after primary series dose 2 and the booster dose, both mRNA-1273.214 primary series (day 57, including all participants with or without evidence of prior SARS-CoV-2 infection at baseline) and booster (day 29, including participants without evidence of prior SARS-CoV-2 infection at baseline) elicited responses that were superior against omicron-BA.1 (geometric mean ratio part 1: 25·4 [95% CI 20·1-32·1] and part 2: 12·5 [11·0-14·3]) and non-inferior against D614G (part 1: 0·8 [0·7-1·0] and part 2: 3·1 [2·8-3·5]), compared with neutralising antibody responses induced by the mRNA-1273 primary series (in a historical comparator group). INTERPRETATION: mRNA-1273.214 was immunogenic against BA.1 and D614G in children aged 6 months to 5 years, with a comparable safety profile to mRNA-1273, when given as a two-dose primary series or a booster dose. These results are aligned with the US Centers for Disease Control and Prevention recommendations for the use of variant-containing vaccines for continued protection against the emerging variants of SARS-CoV-2. FUNDING: Moderna.

No immunological interference or concerns about safety when seasonal quadrivalent influenza vaccine is co-administered with a COVID-19 mRNA-1273 booster vaccine in adults: A randomized trial.

The objective of the study was to assess the safety and immunogenicity of mRNA-1273 COVID-19 booster vaccination when co-administered with an egg-based standard dose seasonal quadrivalent influenza vaccine (QIV). This was a phase 3, randomized, open-label study. Eligible adults aged ≥ 18 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and QIV 2 weeks apart (Seq group) or concomitantly (Coad group). Primary objectives were non-inferiority of haemagglutinin inhibition (HI) and anti-Spike protein antibody responses in the Coad compared to Seq group. 497/498 participants were randomized and vaccinated in the Seq/Coad groups, respectively. The adjusted geometric mean titer/concentration ratios (95% confidence intervals) (Seq/Coad) for HI antibodies were 1.02 (0.89-1.18) for A/H1N1, 0.93 (0.82-1.05) for A/H3N2, 1.00 (0.89-1.14] for B/Victoria, and 1.04 (0.93-1.17) for B/Yamagata; and 0.98 (0.84-1.13) for anti-Spike antibodies, thus meeting the protocol-specified non-inferiority criteria. The most frequently reported adverse events in both groups were pain at the injection site and myalgia. The 2 groups were similar in terms of the overall frequency, intensity, and duration of adverse events. In conclusion, co-administration of mRNA-1273 booster vaccine with QIV in adults was immunologically non-inferior to sequential administration. Safety and reactogenicity profiles were similar in both groups (clinicaltrials.gov NCT05047770).

What is the context? Updated booster shots against COVID-19 disease are likely to offer more protection as the virus is changing over time.It is important for doctors, other healthcare providers and patients to know whether COVID-19 booster vaccines can be given at the same time as other vaccines recommended for adults.What is new? The results of our study showed that an mRNA-based COVID-19 booster vaccine could be given at the same time as the seasonal influenza vaccine.When given together, both vaccines led to immune responses and had side effects that were similar to those observed when they were given at separate times.What is the impact? The potential benefits of administering more than 1 vaccine during a healthcare visit include improved coverage and a reduced number of doctor visits needed to receive all vaccines.Co-administration of COVID-19 booster vaccines and influenza vaccines could be an attractive option for patients and healthcare professionals.

Safety and Immunogenicity of the mRNA-1273 COVID-19 Vaccine in Solid Organ Transplant Recipients.

BACKGROUND: Immunosuppressed individuals, including solid organ transplant recipients (SOTRs), are at high risk for severe COVID-19. METHODS: This open-label, phase 3b trial evaluated mRNA-1273 in 137 adult kidney and 77 liver SOTRs and 20 immunocompetent participants. In Part A, SOTRs received three 100-µg doses of mRNA-1273; immunocompetent participants received 2 doses. In Part B, an additional 100-µg dose was offered ≥4 months post-primary series. Here, we report interim trial results. RESULTS: mRNA-1273 was well-tolerated in SOTRs. Four serious adverse events were considered vaccine-related by the investigator in 3 SOTRs with pre-existing comorbidities. No vaccine-related biopsy-proven organ rejection events or deaths were reported. mRNA-1273 elicited modest neutralizing antibody (nAb) responses after dose 2 and improved responses after dose 3 in SOTRs. Post-dose 3 responses among liver SOTRs were comparable to post-dose 2 responses in immunocompetent participants. Post-additional dose responses were increased in SOTRs regardless of the primary series vaccination. In liver SOTRs, post-additional dose responses were ∼3-fold higher versus post-dose 2 but were lower than immunocompetent participant responses. Most kidney SOTRs received multiple immunosuppressants and had reduced antibody responses versus liver SOTRs. CONCLUSIONS: mRNA-1273 (100 µg) was well-tolerated and dose 3 and the additional dose improved antibody responses among SOTRs.

Safety and Immunogenicity of a Messenger RNA-Based Cytomegalovirus Vaccine in Healthy Adults: Results From a Phase 1, Randomized, Clinical Trial.

BACKGROUND: This phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of mRNA-1647, an mRNA-based cytomegalovirus (CMV) vaccine, in CMV-seronegative and -seropositive adults. METHODS: Participants were randomly assigned to receive 30, 90, 180, or 300 µg of mRNA-1647 or placebo on a 0-, 2-, and 6-month schedule and followed for 12 months after the last dose. RESULTS: A total of 154 (80 CMV-seronegative and 74 CMV-seropositive) participants were enrolled; 118 participants were randomized to mRNA-1647 and 36 to placebo. Mean (SD) age was 32.5 (8.6) and 35.1 (8.9) years in the placebo and mRNA-1647 groups, respectively, in phase B (63% and 64% female) and 42.5 (6.2) and 33.3 (8.7) years, respectively, in phase C (2% and 16% female). No deaths, related serious adverse events, or adverse events of special interest were reported. Most adverse reactions were grade ≤2 severity. Increased neutralizing antibody, binding antibody, and antigen-specific cell-mediated responses were observed across mRNA-1647 treatment groups, regardless of CMV serostatus. CONCLUSIONS: This phase 1, first-in-human trial demonstrated mRNA-1647 has an acceptable safety profile in adults and elicits humoral and cellular immune responses. TRIALS REGISTRATION: NCT03382405; https://clinicaltrials.gov/ct2/show/NCT03382405.

LIGHT signaling through LTßR and HVEM in keratinocytes promotes psoriasis and atopic dermatitis-like skin inflammation.

Psoriasis (PS) and atopic dermatitis (AD) are common skin inflammatory diseases characterized by hyper-responsive keratinocytes. Although, some cytokines have been suggested to be specific for each disease, other cytokines might be central to both diseases. Here, we show that Tumor necrosis factor superfamily member 14 (TNFSF14), known as LIGHT, is required for experimental PS, similar to its requirement in experimental AD. Mice devoid of LIGHT, or deletion of either of its receptors, lymphotoxin ß receptor (LTßR) and herpesvirus entry mediator (HVEM), in keratinocytes, were protected from developing imiquimod-induced psoriatic features, including epidermal thickening and hyperplasia, and expression of PS-related genes. Correspondingly, in single cell RNA-seq analysis of PS patient biopsies, LTßR transcripts were found strongly expressed with HVEM in keratinocytes, and LIGHT was upregulated in T cells. Similar transcript expression profiles were also seen in AD biopsies, and LTßR deletion in keratinocytes also protected mice from allergen-induced AD features. Moreover, in vitro, LIGHT upregulated a broad spectrum of genes in human keratinocytes that are clinical features of both PS and AD skin lesions. Our data suggest that agents blocking LIGHT activity might be useful for therapeutic intervention in PS as well as in AD.

Variation in cervical cancer screening test utilization and results in a United States-based program.

BACKGROUND: Little is known about cervical cancer screening strategy utilization (cytology alone, cytology plus high-risk human papillomavirus [HPV] testing [cotesting], primary HPV testing) and test results in the United States. METHODS: Data from the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program were analyzed for 199,578 persons aged 21-65 years screened from 2019 to 2020. Screening test utilization and results were stratified by demographic characteristics and geographic region. Age-standardized pooled HPV test positivity and genotyping test positivity were estimated within cytology result categories. RESULTS: Primary HPV testing was performed in 592 persons (0.3%). Among the remaining 176,290 persons aged 30-65 years, cotesting was utilized in 72.1% (95% confidence interval [CI] 71.9-72.3%), and cytology alone was utilized in 27.9% (95% CI 27.7-28.1%). Utilization of cytology alone varied by geographic region, ranging from 18.3% (95% CI 17.4-19.1%) to 49.0% (95% CI 48.4-49.6%). HPV genotyping test utilization among those with positive pooled HPV test results was 33.9%. In persons aged ≥30 years, variations in age-adjusted test results by region were observed for pooled HPV-positive test results and for HPV genotyping-positive test results. CONCLUSIONS: Cervical cancer screening strategy utilization and test results vary substantially by geographic region within a national screening program. Variation in utilization may be due to regional differences in screening test availability or the preferences of healthcare systems, screened persons and/or clinicians. Test result variations may reflect differing risk factors for HPV infections by geographic region.

Interim Report of the Reactogenicity and Immunogenicity of Severe Acute Respiratory Syndrome Coronavirus 2 XBB-Containing Vaccines.

BACKGROUND: Monovalent Omicron XBB.1.5-containing vaccines were approved for coronavirus disease 2019 (COVID-19) 2023-2024 immunizations. METHODS: This ongoing, open-label, phase 2/3 study evaluated messenger RNA (mRNA)-1273.815 monovalent (50-µg Omicron XBB.1.5 spike mRNA) and mRNA-1273.231 bivalent (25-µg each Omicron XBB.1.5 and BA.4/BA.5 spike mRNAs) vaccines, administered as fifth doses to adults who previously received primary series, third doses of an original mRNA COVID-19 vaccine, and fourth doses of an Omicron BA.4/BA.5 bivalent vaccine. Interim safety and immunogenicity 29 days after vaccination are reported. RESULTS: Participants (randomized 1:1) received 50-µg of mRNA-1273.815 (n = 50) or mRNA-1273.231 (n = 51); median intervals (interquartile range) from prior BA.4/BA.5 bivalent doses were 8.2 (8.1-8.3) and 8.3 (8.1-8.4) months, respectively. Fold increases in neutralizing antibody (nAb) against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants from prebooster nAb levels were numerically higher against XBB.1.5, XBB.1.16, EG.5.1, BA.2.86, and JN.1 than BA.4/BA.5, BQ.1.1, or D614G on day 29. Monovalent vaccine also cross-neutralized FL.1.5.1, EG.5.1, BA.2.86, HK.3.1, HV.1, and JN.1 variants in a participant subset (n = 20) 15 days after vaccination. Reactogenicity was similar to that of mRNA-1273 vaccines. CONCLUSIONS: XBB.1.5-containing mRNA-1273 vaccines elicit robust, diverse nAb responses against more recent SARS-CoV-2 variants, including JN.1, supporting the XBB.1.5-spike update for COVID-19 vaccines.

Utilizing the 2022 Oncology Navigation Standards of Practice to Revise a Mixed Oncology Navigation Practice Model.

OBJECTIVES: The 2022 Oncology Nursing Society Oncology Navigation Standards of Professional Practice offer a framework for role delineation in oncology navigation. The goal of completing a job task analysis using the standards with four independent navigation teams was to identify a core map of work which would align skills, experience and knowledge with clinical nurse navigators, social work navigators, and patient navigators. Role delineation reduces suboptimal use of resources and inconsistent navigation services. METHODS: An independent job task analysis was conducted with each of the four oncology navigation teams. Patient navigators and clinical nurse navigators were asked to report on each requested task over a 2-week period. The team discussed and determined alignment or misalignment with the standards. This discussion included the request and skill level of each navigator. RESULTS: Sixty percent of the tasks identified in the job task analysis were in alignment with the standards for role and level of care. Thirty percent of the tasks aligned for role, but not for level of care, with nurse navigators performing a high number of non-nursing/clerical tasks. Ten percent were outside the scope of navigation. CONCLUSIONS: Four enterprise opportunities were identified: (1) formalize standards for Tumor Board management, (2) create a core model for essential metrics, (3) establish standardized process for medical record retrieval for new oncology patients, and (4) explore alternative staffing models. IMPLICATIONS FOR NURSING PRACTICE: Using a job task analysis allows time for meaningful exploration of roles and scope of work completed by the team. High work volume for navigation teams often leads to a "this is the way we've always done it" mentality. A job task analysis provides a structured approach with dedicated time and a safe space for navigators to "think critically" about their daily work, identify opportunities for change, and progress using this framework.

Are National Breast and Cervical Cancer Early Detection Program Recipients Providing Services in Counties Heavily Burdened by Breast and Cervical Cancer?

INTRODUCTION: Alignment of National Breast and Cervical Cancer Early Detection Program (NBCCEDP) clinical services with the spatial distribution of breast and cervical cancer burden is essential to maximizing programmatic impact and addressing cancer disparities. This study identified spatial clustering of breast and cervical cancer burden scores and assessed whether and to what extent NBCCEDP clinical services were associated with clusters for the 5-year period, 2015-2019. METHODS: We examined burden scores for spatial clustering using Local Indicators of Spatial Association (LISA) tests in GeoDA. We then used t-tests to compare the NBCCEDP 5-year average percentage of eligible women served clinical breast and cervical cancer services between hotspot (high burden) and coolspot clusters. RESULTS: There was statistically significant spatial clustering in the pattern of breast and cervical cancer burden scores across counties, with hotspot clusters mostly observed in the Southern region, Idaho and Nevada. For both breast and cervical cancer, higher percentages of eligible women received breast and cervical cancer clinical services in coolspot clusters compared to hotspot clusters during each year from 2015-2019. CONCLUSION: NBCCEDP clinical services can help reduce breast and cervical cancer burden. Yet, during 2015-2019, increased service delivery was not aligned with the spatial distribution of counties with greater breast and cervical cancer burdens. NBCCEDP recipients may improve their impact on breast and cervical cancer burden by prioritizing and consistently increasing service delivery in cancer burden hotspot clusters if they have not already maximized their resources in these areas.

Variation in State-Level Mammography Use, 2012 and 2020.

OBJECTIVES: Mammography is a screening tool for early detection of breast cancer. Uptake in screening use in states can be influenced by Medicaid coverage and eligibility policies, public health outreach efforts, and the Centers for Disease Control and Prevention-funded National Breast and Cervical Cancer Early Detection Program. We described state-specific mammography use in 2020 and changes as compared with 2012. METHODS: We estimated the proportion of women aged ≥40 years who reported receiving a mammogram in the past 2 years, by age group, state, and demographic and socioeconomic characteristics, using 2020 Behavioral Risk Factor Surveillance System data. We also compared 2020 state estimates with 2012 estimates. RESULTS: The proportion of women aged 50-74 years who received a mammogram in the past 2 years was 78.1% (95% CI, 77.4%-78.8%) in 2020. Across measures of socioeconomic status, mammography use was generally lower among women who did not have health insurance (52.0%; 95% CI, 48.3%-55.6%) than among those who did (79.9%; 95% CI, 79.3%-80.6%) and among those who had a usual source of care (49.4%; 95% CI, 46.1%-52.7%) than among those who did not (81.0%; 95% CI, 80.4%-81.7%). Among women aged 50-74 years, mammography use varied across states, from a low of 65.2% (95% CI, 61.4%-69.0%) in Wyoming to a high of 86.1% (95% CI, 83.8%-88.3%) in Massachusetts. Four states had significant increases in mammography use from 2012 to 2020, and 8 states had significant declines. CONCLUSION: Mammography use varied widely among states. Use of evidence-based interventions tailored to the needs of local populations and communities may help close gaps in the use of mammography.

TNF-like weak inducer of apoptosis inhibition is comparable to IL-13 blockade in ameliorating atopic dermatitis inflammation.

BACKGROUND: Targeting IL-13 is highly efficacious in patients with Th2-biased atopic dermatitis (AD), but inhibition of other inflammatory molecules might also limit disease. We investigated the importance of the TNF family cytokine TNF-like weak inducer of apoptosis (TWEAK; TNFSF12) to keratinocyte dysregulation and the pathogenesis of AD in mice and also tested if blocking TWEAK has a similar therapeutic effect as targeting IL-13. METHODS: Conditional knockout mice lacking Fn14 (TNFRSF12A), the receptor for TWEAK, only in keratinocytes, were repetitively sensitized with house dust mite allergen and analyzed for AD-like skin inflammation. To determine the translational potential, wild-type mice with AD were therapeutically treated with anti-TWEAK and/or anti-IL-13 antibodies, and skin inflammation was assessed. RESULTS: Mice deficient in Fn14 in keratinocytes were resistant to developing maximal clinical features of AD, exhibiting reduced epidermal hyperplasia and dermal thickening, less skin infiltration of immune cells, and downregulated inflammatory gene expression. Moreover, therapeutic neutralization of TWEAK in wild-type mice with AD reduced all of the pathological features to a comparable extent as blocking IL-13. CONCLUSIONS: The activity of TWEAK in keratinocytes contributes to AD development, and neutralizing TWEAK represents a future potential therapeutic option in human AD similar to targeting IL-13.

Efficacy and Safety of an mRNA-Based RSV PreF Vaccine in Older Adults.

BACKGROUND: Respiratory syncytial virus (RSV) can cause substantial morbidity and mortality among older adults. An mRNA-based RSV vaccine, mRNA-1345, encoding the stabilized RSV prefusion F glycoprotein, is under clinical investigation. METHODS: In this ongoing, randomized, double-blind, placebo-controlled, phase 2-3 trial, we randomly assigned, in a 1:1 ratio, adults 60 years of age or older to receive one dose of mRNA-1345 (50 µg) or placebo. The two primary efficacy end points were the prevention of RSV-associated lower respiratory tract disease with at least two signs or symptoms and with at least three signs or symptoms. A key secondary efficacy end point was the prevention of RSV-associated acute respiratory disease. Safety was also assessed. RESULTS: Overall, 35,541 participants were assigned to receive the mRNA-1345 vaccine (17,793 participants) or placebo (17,748). The median follow-up was 112 days (range, 1 to 379). The primary analyses were conducted when at least 50% of the anticipated cases of RSV-associated lower respiratory tract disease had occurred. Vaccine efficacy was 83.7% (95.88% confidence interval [CI], 66.0 to 92.2) against RSV-associated lower respiratory tract disease with at least two signs or symptoms and 82.4% (96.36% CI, 34.8 to 95.3) against the disease with at least three signs or symptoms. Vaccine efficacy was 68.4% (95% CI, 50.9 to 79.7) against RSV-associated acute respiratory disease. Protection was observed against both RSV subtypes (A and B) and was generally consistent across subgroups defined according to age and coexisting conditions. Participants in the mRNA-1345 group had a higher incidence than those in the placebo group of solicited local adverse reactions (58.7% vs. 16.2%) and of systemic adverse reactions (47.7% vs. 32.9%); most reactions were mild to moderate in severity and were transient. Serious adverse events occurred in 2.8% of the participants in each trial group. CONCLUSIONS: A single dose of the mRNA-1345 vaccine resulted in no evident safety concerns and led to a lower incidence of RSV-associated lower respiratory tract disease and of RSV-associated acute respiratory disease than placebo among adults 60 years of age or older. (Funded by Moderna; ConquerRSV ClinicalTrials.gov number, NCT05127434.).

Stochastic Interventional Vaccine Efficacy and Principal Surrogate Analyses of Antibody Markers as Correlates of Protection against Symptomatic COVID-19 in the COVE mRNA-1273 Trial.

The COVE trial randomized participants to receive two doses of mRNA-1273 vaccine or placebo on Days 1 and 29 (D1, D29). Anti-SARS-CoV-2 Spike IgG binding antibodies (bAbs), anti-receptor binding domain IgG bAbs, 50% inhibitory dilution neutralizing antibody (nAb) titers, and 80% inhibitory dilution nAb titers were measured at D29 and D57. We assessed these markers as correlates of protection (CoPs) against COVID-19 using stochastic interventional vaccine efficacy (SVE) analysis and principal surrogate (PS) analysis, frameworks not used in our previous COVE immune correlates analyses. By SVE analysis, hypothetical shifts of the D57 Spike IgG distribution from a geometric mean concentration (GMC) of 2737 binding antibody units (BAU)/mL (estimated vaccine efficacy (VE): 92.9% (95% CI: 91.7%, 93.9%)) to 274 BAU/mL or to 27,368 BAU/mL resulted in an overall estimated VE of 84.2% (79.0%, 88.1%) and 97.6% (97.4%, 97.7%), respectively. By binary marker PS analysis of Low and High subgroups (cut-point: 2094 BAU/mL), the ignorance interval (IGI) and estimated uncertainty interval (EUI) for VE were [85%, 90%] and (78%, 93%) for Low compared to [95%, 96%] and (92%, 97%) for High. By continuous marker PS analysis, the IGI and 95% EUI for VE at the 2.5th percentile (519.4 BAU/mL) vs. at the 97.5th percentile (9262.9 BAU/mL) of D57 Spike IgG concentration were [92.6%, 93.4%] and (89.2%, 95.7%) vs. [94.3%, 94.6%] and (89.7%, 97.0%). Results were similar for other D29 and D57 markers. Thus, the SVE and PS analyses additionally support all four markers at both time points as CoPs.