Human Vaccines & Immunotherapeutics

Introduction: Recommendations from physicians and peers play a crucial role in promoting vaccination. This study evaluated differences in recommendations to others regarding four vaccines with varying efficacy (seasonal influenza, measles, human papillomavirus [HPV], and coronavirus disease 2019 [COVID-19]) between physicians and the general public and examined the impact of birth-year-based vaccination policy changes on these recommendations. Methods: This cross-sectional study was conducted in February 2026 among 492 physicians and 5,252 members of the general public in Japan. Consistency in recommendations across the four vaccines was assessed using the intraclass correlation coefficient (ICC[3,1]), and group differences were examined using a two-way mixed-design analysis of covariance. Multilevel regression discontinuity analyses were performed to evaluate the effects of birth-year-based vaccination policy. Results: Physicians showed significantly stronger recommendations to others than the general public, and their recommendation patterns generally reflected vaccine efficacy. However, physicians showed lower consistency across vaccine types than the general public (ICC[3,1]), driven primarily by heterogeneity in COVID-19 vaccine recommendations. Regression discontinuity analyses showed that birth-year-based vaccination policy, including routine vaccination opportunities, was significantly associated with recommendations to others for measles and HPV vaccines, independently of perceived benefits and risks. Conclusion: To improve vaccination coverage from a public health perspective, it is important for physicians to provide effective vaccination recommendations to the general public on a broader scale; however, it is also necessary to address the heterogeneity in vaccine-specific recommendation patterns among physicians, as observed for COVID-19. Routine vaccination opportunities may increase vaccination coverage not only through the routine vaccination program itself but also through peer effects among the general public. Vaccination policy may therefore influence vaccination coverage not only in the current generation but also in future generations. Designing vaccination policy should consider its long-term impact on future vaccination coverage as well as herd immunity.

We compared the immunogenicity of three licensed egg-based inactivated influenza vaccines, including TetrAnflu (Sinovac quadrivalent), Fluarix Tetra (GSK quadrivalent), and Vaxigrip (Sanofi trivalent), in adult healthcare workers in Hong Kong during the 2025/26 season. Paired pre- and post-vaccination sera from age- and sex-matched recipients (n=30 to 40 per group) were tested by hemagglutination-inhibition assays against vaccine strains. After adjustment for age, sex, and sampling interval, the vaccines induced broadly comparable rises in antibody titers, proportions achieving titers >=40, and seroconversion rates, with a superior response to A(H1N1) after TetrAnflu. These real-world findings support the interchangeability of these vaccines for influenza vaccination programs.

Background: Vaccination of people with HIV (PWH) on suppressive antiretroviral therapy (ART) represents a novel approach for evaluating candidate broadly neutralizing antibody (bnAb) immunogens for preventive and therapeutic HIV vaccines. Given pre-existing immunity in PWH, the safety of this approach requires careful assessment prior to broader application. Here, we report on the design and safety of the RENEW-SHCS study which evaluates the immunization of PWH with BG505 SOSIP.v4.1-GT1.1, an immunogen engineered to induce precursors of CD4 binding site (CD4bs)- and V2-apex targeting bnAbs. Methods. RENEW-SHCS is a phase I, open-label, non-randomized vaccination trial evaluating a single dose of the recombinant germline-targeting envelope trimer BG505 SOSIP.v4.1-GT1.1 (GT1.1), adjuvanted with 3M052-AF and Aluminum hydroxide (alum), in PWH on suppressive ART enrolled from the Swiss HIV Cohort Study. Participants were previously classified as bnAb or non-neutralizing antibody (nnAb) inducers, with a target enrollment of 15 per group, and were monitored for safety and immunogenicity for 24 weeks while continuing standard ART. Due to an out-of-specification stability measurement of adjuvant 3M052-AF the trial was paused after 23 immunizations and subjected to an unscheduled interim safety and reactogenicity assessment comprising protocol defined outcome measures (adverse events, clinical laboratory measurements and HIV-1 viral load). Results. Twenty-three participants (10 bnAb and 13 nnAb inducers, median age 59 years, 17 male / 6 female) were vaccinated between March and August 2025 before interruption of the trial. All participants completed follow-up with full protocol adherence. The interim-safety analysis confirmed that no vaccine-related serious adverse events occurred. Solicited local (96%) and systemic (83%) reactions were common, predominantly grade 1-2, transient, and self-limited. Transient laboratory changes occurred but mostly remained within the normal range, with no vaccine-related grade 3 abnormalities. We observed predominantly transient local and systemic reactions, which were similar or milder to the reactogenicity profile reported for immunization of adult people without HIV (PWOH) with GT1.1 adjuvanted with AS01b reported in the IAVI C101 trial. No viral rebound under ART occurred. One participant experienced two viral blips (>50 HIV-1 RNA copies/ml), one before and one 16 weeks after vaccination with subsequent re-suppression. All others maintained viral suppression (<50 copies/ml) throughout follow-up. Conclusion. RENEW-SHCS demonstrated a favorable safety and reactogenicity profile of single dose immunization with GT1.1 in PWH, comparable to that observed in PWOH. The findings of this phase I study support the feasibility of vaccinating ART-treated PWH in trials of preventive and therapeutic HIV vaccine strategies.

BACKGROUND Current polio vaccines face challenges including vaccine-derived poliovirus and high-containment manufacturing. We evaluated a recombinant trivalent virus-like particle (VLP)-based poliovirus vaccine (VPV) for safety and immunogenicity in a first-in-human phase 1 trial. METHODS In this randomized, observer-blind, active-controlled trial, 72 healthy adults (18 to 54 years) were assigned (1:1:1:1) to receive a single dose of VPV at low (45:8:25 D-antigen units [DU] + 0.1 mg aluminum phosphate [AP]), medium (45:8:25 DU + 0.3 mg AP), or high (90:12:45 DU + 0.3 mg AP) doses, or conventional inactivated poliovirus vaccine (cIPV). Primary outcomes were safety and tolerability. Secondary outcomes included neutralizing antibody titers through day 180. RESULTS No serious adverse events or Grade 3 reactions were reported. Solicited adverse events were reported in 77.8%, 55.6%, and 72.2% of the low-, medium-, and high-dose VPV groups, respectively, and 66.7% in the cIPV group. By day 29, VPV induced dose-dependent neutralizing antibody responses. For serotypes 1 and 2, the high-dose VPV group achieved geometric mean titers (GMTs) of 73,582 (95% CI, 31,198-173,545) and 110,623 (95% CI, 59,276-206,451), respectively, comparable to cIPV at 45,161 (95% CI, 20,973-97,244) and 112,361 (95% CI, 58,280-216,625). Although serotype 3 GMTs were lower for the high-dose VPV at 18,905 (95% CI, 8737-40,906) than for cIPV at 61,431 (95% CI, 31,123-121,251), 100% of high-dose VPV recipients achieved neutralizing titers [&ge;]1:1024. CONCLUSIONS A single dose of VPV was safe and highly immunogenic, supporting its potential as a next-generation vaccine to advance global polio eradication. (Funded by the Gates Foundation and Tianjin Leading Enterprises Innovative project 23YDLQSY00100; ClinicalTrials.gov number, NCT06101173).

Objectives: To develop and validate a disease-specific patient-reported outcome (PRO) measure for spinal and bulbar muscular atrophy (SBMA). Methods: A three-stage sequential design was adopted. Items were generated through qualitative interviews with patients with SBMA and expert review, refined using quantitative analyses, and evaluated for reliability and validity in independent cohorts from Japan and the United States. Results: Interviews with 12 patients generated 234 candidate items, which were refined into a final 31-item SBMAPRO comprising five domains based on an online survey of 106 patients. Internal consistency across domains ranged from Cronbach's alpha values of 0.651 to 0.901. In the Japanese cohort, test-retest reliability yielded intraclass correlation coefficients of 0.941 for physical function, 0.877 for mental health, and 0.858 for social function. Construct validity was examined through correlations with disease-specific functional measurements and the 36-Item Short Form Survey (SF-36). The SBMAPRO correlated with the SBMA Functional Rating Scale (r = -0.826, p <0.001) and with the SF-36 mental health (r = -0.693, p <0.001) and social functioning (r = -0.617, p <0.001) domains. In subscale analyses, the SBMAPRO social domain was associated with trunk-lower limb-related functional impairment (r = -0.587, p < 0.001). Similar patterns were observed in the American cohort. Conclusion: The SBMAPRO demonstrated reliability and validity in Japanese and American cohorts. Associations between mental and social domains and trunk-lower limb dysfunction suggest that mobility impairment may contribute to psychological burden and restricted social participation in SBMA, indicating that this disease-specific PRO may complement clinician-rated measures.

Introduction Hepatitis E virus (HEV) in pregnancy is associated with high maternal and perinatal morbidity and mortality. The safety and efficacy of the recombinant protein HEV vaccine (HEV239, Hecolin) have been established in non-pregnant adult populations but there is limited information among pregnant women. This trial has two co-primary objectives: 1) to assess pregnancy-related and/or serious safety events among pregnant women between 14 and 34 weeks of gestation receiving two Hecolin doses four weeks apart compared to placebo recipients, and 2) to determine immune non-inferiority of pregnant recipients of two Hecolin doses four weeks apart compared to non-pregnant women. Methods and Analysis This is a multi-site, randomized, observer-blinded, placebo-controlled vaccine safety and immunogenicity trial in pregnant women and non-pregnant women of reproductive age in Karachi, Pakistan. A total of 2,358 healthy women will be enrolled, including 2,208 pregnant women between 14 and 34 weeks of gestation, who will be randomized in a 1:1 ratio (stratified by gestational age, 14-27 and 28-34 weeks) to receive either Hecolin or a normal saline placebo in two doses administered 1 month apart during pregnancy and a third dose administered postpartum, approximately 5 months after the second dose. A third arm of 150 non-pregnant women aged 16-45 years will receive Hecolin on 0, 1, and 6 months. The co-primary outcomes will be (i) the proportion of pregnancy-related AESIs and SAEs in pregnant participants from the first dose until the end of study follow-up, compared with placebo, and (ii) the geometric mean concentration (GMC) of anti-HEV IgG at four weeks after the second dose, comparing pregnant vaccine recipients with non-pregnant vaccine recipients (non-inferiority margin of 0.67 for the GMC ratio). Immunogenicity will be evaluated in a pre-specified subset of 300 participants receiving Hecolin, including 150 pregnant participants and 150 non-pregnant participants. Secondary outcomes will include maternal, neonatal, and infant safety outcomes, as well as immunogenicity according to the number of Hecolin doses received and the trimester of vaccination. Ethics and Dissemination The trial was approved by the National Bioethics Committee (NBC) of Pakistan (Reference number: 4-87/NBC-910), the institutional Ethics Review Committee (ERC) of the Aga Khan University (Reference number: 8298), and the Institutional Review Board (IRB) of the International Vaccine Institute (IVI) (Reference number: 2022-007). All participants will provide written informed consent in accordance with Good Clinical Practice. The results will be submitted to World Health Organization (WHO) Strategic Advisory Group of Experts in Immunization (SAGE), and disseminated through conference presentations, and peer-reviewed publications.

During the 2025-26 respiratory virus season, changes to COVID-19 vaccine eligibility, recommendations, and communication may have made vaccination follow-through especially challenging. Under-vaccination may reflect not only lack of willingness, but also breakdowns between willingness and uptake. We analyzed data from 3,390 adults in the CHASING COVID Cohort who completed assessments in August 2025 and March 2026 to examine gaps between vaccine willingness and subsequent influenza and COVID-19 vaccination. Vaccine willingness was defined using prior-season vaccination and stated intention to vaccinate during the 2025-26 respiratory virus season. In August 2025, 73% of participants were influenza vaccine willing and 68% were COVID-19 vaccine willing. Among vaccine-willing participants, 17% and 39% were unvaccinated for influenza and COVID-19, respectively, by March 2026. Absence of prior-season vaccination was the strongest predictor of not vaccinating for influenza and COVID-19, respectively (aRR [95% CI]: 4.04 [3.44-4.74]; 3.01 [2.72-3.34]). Non-vaccination was also associated with food insecurity (1.99 [1.66-2.37]; 1.47 [1.33-1.63]), any healthcare barrier (1.89 [1.57-2.28]; 1.51 [1.36-1.67]), and being not at all confident in vaccine safety (2.95 [2.15-4.05]; 2.21 [1.88-2.59]). Trajectory analyses suggested willingness-uptake gaps reflected incomplete follow-through on intentions and discontinuation among some prior vaccinators. Commonly reported reasons among vaccine-willing non-vaccinators included difficulty finding a convenient time, place, or appointment and, for COVID-19, lack of healthcare provider recommendation. Findings among non-vaccinated adults with prior or stated openness to vaccinate highlight missed opportunities and suggest avenues to improve coverage through strategies that reinforce vaccine confidence, reduce access and logistical barriers, and make vaccination easier to complete.

Seeking a simple vaccine to protect against all cancer-associated human papillomaviruses (HPV), L2 residues 17-36 of both HPV16 and HPV31 displayed on the surface of an Adeno-Associated Virus-Like Particle (AAVLP-HPV) was developed. Here, a phase 1 randomized, placebo-controlled, double-blind clinical study has been conducted in 20 male and female subjects at a single dose level (20 ug) without an adjuvant. AAVLP-HPV vaccine administration was safe and well tolerated. Repeat vaccination with AAVLP-HPV elicited L2-specific neutralizing antibodies of modest titer in serum. Antibodies cross-reactive with L2 of diverse HPV types were detected, but responses were weak in most vaccinees. We conclude that while AAVLP-HPV vaccination is well tolerated, an adjuvant is likely needed to consistently elicit durable and broadly neutralizing responses.

Cross-reactive antibodies against dengue virus are known to cause antibody-dependent enhancement (ADE) of infection or disease severity under specific conditions. In our previous study, we showed that primary immunization with the COVID-19 vaccine induces induces cross-reactive IgG causing ADE against dengue. In the present study, we investigated the influence of IgG Fc-glycosylation (analyzed by LC-MS/MS) on ADE mediated by cross-reactive IgG against dengue from IgG against SARS-CoV-2. We found a clear correlation between anti-DENV2 E IgG2 galactosylation and the ADE capacity of cross-reactive IgG against dengue in individuals vaccinated against COVID-19. IgG2 sialylation increased over time; however, it was not correlated with ADE capacity. This phenomenon was restricted to IgG2, whereas anti-DENV2 E IgG1 Fc-glycosylation remained stable after COVID-19 vaccination.

Individuals with NF2-related schwannomatosis (NF2-SWN) experience a complex constellation of physical, emotional, and social symptoms that substantially impact quality of life (QoL). Although disease-specific patient-reported outcome measures are increasingly important for evaluating treatment benefit in clinical trials, existing NF2-SWN QoL measures have limitations in content coverage and sensitivity to change. This study describes the development and initial validation a new disease-specific QoL assessment -- the Quality of Life Evaluation in NF2-related Schwannomatosis Trials (QUEST). Using a three-phase, mixed-methods approach, items were generated through concept elicitation interviews with individuals with NF2-SWN and clinicians, prioritized via patient survey data, and refined through iterative cognitive debriefing procedures. The resulting 21-item QUEST assesses the extent to which NF2-SWN has negatively impacted a persons daily life over the past seven days. Initial psychometric evaluation was conducted in an international sample of 174 individuals with NF2-SWN aged 15 years and older (117 women (67%), 158 White individuals (89%)). Exploratory factor analysis supported a four-factor structure, and the total score demonstrated excellent internal consistency and strong test-retest reliability. Evidence of construct validity was demonstrated through hypothesized associations with disease-specific, generic, and domain-specific QoL measures, as well as known-groups validity based on self-reported disease severity and number of prior surgeries. Incremental validity analyses indicated that QUEST explained unique variance beyond existing measures. Together, findings support the QUEST as a reliable and valid disease-specific QoL measure with strong content validity and feasibility for use as a clinical trial endpoint in NF2-SWN.

Colombia has been internationally recognised as a paradigmatic case of vaccine confidence crisis since the 2014 Carmen de Bolivar event, and national HPV vaccination coverage remains far below the World Health Organization 2030 target. Most published evidence focuses on female adolescents and on cervical cancer; the perception of the HPV vaccine in university-age populations of both sexes--and across the broader spectrum of HPV-attributable disease--remains comparatively understudied. We aimed to describe the influence of biopsychosocial determinants on HPV vaccine perception among university students of both sexes in Cucuta, Norte de Santander, Colombia. We conducted a cross-sectional study with a mixed quantitative-qualitative approach in 2024 among four universities (Universidad de Santander, Universidad Francisco de Paula Santander, Universidad de Pamplona and Universidad Libre; combined enrolment 21,033 students). Using convenience sampling stratified by institution, 750 actively enrolled undergraduate students of both sexes (18-60 years) completed a structured online questionnaire adapted from previously validated instruments. The instrument captured sociodemographic information, HPV knowledge and HPV vaccine perception. Data were analysed using Students t-test, one-way analysis of variance, Tukey post-hoc tests, effect sizes and 95% confidence intervals, with a 0.05 significance threshold. Of 750 respondents, 54.2% were women, 61.3% were under 20 years of age, and 75.1% attended public universities. HPV knowledge was high in 39.2%, intermediate in 42.4% and low in 18.4%; women and students aged 26 years or older displayed higher knowledge. Although 91.2% had heard of HPV and 82.5% knew that both sexes could acquire it, recognition of clinical manifestations and complications was uneven: cervical cancer 51.7%, penile cancer 30.5%, vaginal warts 45.9% and warts in the penis, larynx, anus or rectum 34.0%. Vaccine-specific knowledge was low in 77.1%, with men disproportionately represented (85.9% versus 69.5% in women). Overall positive perception of HPV vaccination was 66.6%, slightly higher in women (68.8%) than men (63.9%), in students aged 26 years or older (70.1%) and in students from private universities (68.1% versus 65.9%). Inferential analysis identified sex (Cohens d = -0.357), type of university (d = 0.189) and HPV knowledge (partial eta-squared = 0.096) as the only significant determinants. Age, socioeconomic stratum, age at sexual debut and vaccine-specific knowledge did not reach meaningful significance. HPV vaccine perception was predominantly positive but conditioned by three biopsychosocial determinants, with HPV knowledge as the primary driver. The persistent gender gap reflects historical anchoring of HPV messaging in cervical disease and female-targeted campaigns. Public-health strategies should adopt comprehensive, gender-inclusive educational interventions that explicitly visibilise non-cervical HPV-related cancers and address both sexes from a common evidence base.

Introduction: Synthetic oligopeptides provide a rapid and cost-efficient approach to developing antibodies and diagnostics for emerging viral variants. Methods: This study computationally and experimentally characterized a synthetic peptide analog of the SARS-CoV-2 spike subdomain 2 major disulfide loop (SD2MDL), designated S621 (CPVAIHADQLTPTWRVYSTC). Binding affinity was computationally estimated using the Heuristic Affinity Prediction Tool for Immune Complexes (HAPTIC), while experimental validation was performed using enzyme-linked immunosorbent assay (ELISA) with rabbit-derived antipeptide antibodies. Clinical diagnostic accuracy testing was done using plasma samples from RT-PCR-confirmed COVID-19 patients and pre-COVID-19 controls. Results: S621 demonstrated nanomolar binding affinity (Kdapp = 1.14 nM) and high avidity (3.67 nM), closely matching HAPTIC predictions (3.54 nM). Diagnostic evaluation yielded a sensitivity of 89.92% and specificity of 27.79%, corresponding to an overall accuracy of 71.79%. Discussion: These findings demonstrate that a single synthetic peptide derived from a conserved spike subdomain can function as a high-affinity surrogate for full-length antigens, supporting its potential application in rapid peptide-based immunodiagnostics.

Development of an effective HCV vaccine requires the induction of both broadly neutralizing antibodies (bnAbs) and a robust cellular response. One issue that has arisen is that HCV subunit vaccines have limited immunogenicity, thus requiring multivalent formats in order to elicit a robust anti-HCV immune response. Toward that end, nanoparticle vaccines possess the ability to facilitate a controlled multivalent presentation and trafficking to lymph nodes, where they can interact with both arms of the immune system. Here, we used a soluble, secreted form of E1E2 (sE1E2) to assemble native E1E2 into a nanoparticle platform using a post-purification coupling assembly system. Nanoparticles were assembled by purifying sE1E2 containing a C-terminal SpyTag and an mi3-SpyCatcher fusion separately and covalently coupling the components via incubation. Free sE1E2-SpyTag was removed from nanoparticle preparations via gel filtration. The sE1E2-mi3 nanoparticles are fully competent to bind conformation-dependent bnAbs, indicating retention of a native assembly in the nanoparticle format. Electron microscopy analysis showed a clear incorporation of sE1E2 on the surface of the nanoparticle. Immunogenicity of sE1E2-mi3 nanoparticles was examined relative to sE1E2 alone and membrane-bound E1E2 (mbE1E2) following inoculation of groups of CD1 mice. Assessment of the immunogenicity of the sE1E2-mi3 nanoparticles showed that the nanoparticle assembly has a similar immunogenicity profile to that of mbE1E2 after only a prime and one boost, and overall superior to sE1E2. This proof-of-principle study sets the stage for further exploration of nanoparticles and other multivalent platforms for the development of E1E2-based vaccines. ImportanceHepatitis C virus infects approximately 50 million people, and at present no effective HCV vaccine exists. Due to the high sequence variability of HCV and the resulting difficulty in developing a vaccine that elicits a broadly neutralizing response, multiple efforts are underway to enhance the immunogenicity of HCV vaccine candidates. In this study, we incorporated native soluble, secreted E1E2 (sE1E2) into a 60-mer nanoparticle via the SpyTag-SpyCatcher system and covalent isopeptide bond attachment using the purified components. These nanoparticles are antigenically intact and elicit a neutralizing antibody response at an earlier time point in the immunization regimen than the corresponding subunit vaccine. These studies show that a well-characterized sE1E2 platform compatible with multiple genotypes can be coupled to nanoparticles for use as a vaccine candidate.

Evidence on vaccine effectiveness (VE) of 2025-26 COVID-19 vaccines is limited. We estimated VE of BNT162b2 LP.8.1-adapted vaccine among non-immunocompromised adults [&ge;]65 years through December 2025 using linked claims and immunization registry data from two U.S. states. VE against COVID-19-related ED/UC encounters was 48% (95% CI:19, 66).

Background: Responses to vaccination programmes vary widely, with contrasting perceptions of benefits and harms. This study aimed to provide a contemporary characterization of distinct groups of respondents by moving past traditional "pro" versus "anti" vaccination binaries. The results captured the complex spectrum of vaccine sentiment to directly inform the next strategic phases of a multi-year public health campaign regarding vaccine perceptions and behaviours within the diverse population of London. Methods: Data came from the 2024 Why We Get Vaccinated survey conducted in London, UK using a community-based participatory approach. Participants answered vaccine-related questions based on previous vaccine uptake, future willingness to vaccinate (WTV), perceived effectiveness, and safety concerns. We employed Bayesian Binomial logistic regression to identify sociodemographic predictors of individual responses. Subsequently, a Bayesian Nonparametric Latent Class Analysis (BNP-LCA) using a Dirichlet Process Mixture model was used to identify distinct groups and their sociodemographic compositions. Results: The LCA identified five distinct classes. Class 1, the Consistent Uptakers (37.2%), exhibited high vaccine uptake (89.2%) and near-universal belief in efficacy (98.0%) with minimal safety concerns. Class 2, the Concerned Uptakers (17.5%), maintained high WTV (72.2%) despite significant concerns regarding adverse effects (71.2%). Class 3, the Consistent Refusers (18.4%), demonstrated uniform rejection of vaccines and high levels of safety concern (74.4%). Class 4, the Unconcerned Refusers (20.8%), acknowledged vaccine effectiveness (98.4%) but showed very low uptake (1.7%), possibly due to low perceived personal risk rather than active resistance. Class 5, the Undecided/Uninformed (6.0%), was characterized by pervasive uncertainty and "Don't Know" responses regarding efficacy (80.3%) and vaccination intent. Sociodemographic analysis revealed that residential instability, i.e renting, and caregiving responsibilities were significant barriers to uptake, while older age and retirement were the strongest positive predictors. Conclusions: Vaccine behaviour and attitudes in London are a multidimensional construct. The discovery of "Unconcerned Refusers" and "Concerned Uptakers" highlights that "one-size-fits-all" public health campaigns may not be effective. Tailored public health messaging is required to address the specific uncertainties and socio-economic barriers identified across these distinct profiles. These findings provide a functional framework that will directly guide upcoming resource allocation, messaging adaptations, and policy decisions for the next iterations of the ongoing campaign

Background: Anti-amyloid antibody therapies have changed the clinical pathway for early Alzheimer disease (AD). Lecanemab and donanemab are now clinically available in many countries, including Japan, and their use requires biomarker confirmation, repeated magnetic resonance imaging monitoring, management of amyloid-related imaging abnormalities, infusion capacity, staff resources, and shared decision-making. In Japan, these treatments are provided under the universal public health insurance system and are regulated by the optimal use guidelines. Therefore, it is important to understand not only the number of treated patients but also how specialists perceive clinical, logistical, and policy challenges in routine practice. Objective: This paper describes the protocol for a nationwide anonymous online survey of dementia specialists in Japan. The survey aims to evaluate the real-world implementation of anti-amyloid antibody therapies, including current clinical practice, facility readiness, perceived barriers, possible policy solutions, and physician preferences assessed using a discrete choice experiment and best-worst scaling. Methods: This is a prospective, cross-sectional, anonymous online survey using Google Forms. The survey targets board-certified specialists of the Japanese Society for Dementia Research and the Japanese Psychogeriatric Society, with a main focus on physicians who have completed the official training course required for anti-amyloid antibody therapy. The questionnaire includes items on respondent and facility characteristics, perceived value of treatment, treatment experience, diagnostic and eligibility assessment, amyloid and APOE testing, MRI monitoring, infusion capacity, continued-administration facilities, blood-based biomarkers, preclinical AD, a discrete choice experiment, and best-worst scaling. Among respondents routed to the DCE section, the discrete choice experiment asks respondents to choose between hypothetical anti-amyloid antibody treatment profiles for early AD, defined by expected efficacy, risk of amyloid-related imaging abnormalities requiring treatment interruption or discontinuation, treatment duration, visit frequency, waiting time, and monthly out-of-pocket cost. Best-worst scaling evaluates the relative importance of policy and system-level solutions. Results: Data collection started on June 3, 2026, and is planned to close on June 30, 2026. This protocol was prepared before data lock and before any outcome analyses. The main results will be reported after data cleaning and analysis according to the prespecified analysis plan. Conclusions: This protocol describes a nationwide survey designed to clarify clinical, logistical, and policy challenges in the implementation of anti-amyloid antibody therapies in Japan. By publishing the survey design and analysis plan before data lock, this study aims to improve transparency and interpretability. The findings will help identify where Japanese dementia specialists perceive bottlenecks in diagnosis, biomarker testing, safety monitoring, infusion delivery, continued administration, and reimbursement. They may also inform policy discussions on APOE testing, blood-based biomarkers, regional care coordination, and service reimbursement for anti-amyloid antibody therapy.

Background: The N-terminal ectodomain (NTE) of the SARS-CoV-2 membrane (M) glycoprotein is a short, flexible region that remains exposed on the virion surface and exhibits immunogenic potential across multiple coronaviruses. Despite its small size and conformational plasticity, this region contains conserved linear epitopes that may serve as practical surrogates for full-length proteins in serological diagnostics. Objective: To develop and evaluate a synthetic peptide-based diagnostic assay targeting the NTE of the SARS-CoV-2 M protein. Methods: Epitope prediction, peptide synthesis, and antibody affinity assays were performed to design homomultivalent peptide analogs that exploit avidity effects through disulfide polymerization. The resulting peptide antigens were tested in an enzyme-linked immunosorbent assay (ELISA) using clinical samples from RT-PCR-confirmed COVID-19 patients and biobanked controls. Results: The selected peptide analogs (M1, M1i, M1s) corresponded to a conserved surface-exposed motif of the SARS-CoV-2 M protein. Polymeric M1 exhibited a twofold gain in apparent affinity (Kdapp = 4.33 nM) compared with the monomeric form (Kdapp = 8.00 nM). Clinical validation using 1,222 patient samples yielded a sensitivity of 95.26% and specificity of 52.27%, with an overall diagnostic accuracy of 88.70%. Conclusion: The M peptide analogs demonstrate that synthetic peptide antigens can serve as stable, high-sensitivity surrogates for whole-protein assays. This design principle may be applied to other emerging pathogens where rapid assay development and scalability are critical. Keywords: Peptides, Antibodies, COVID-19, Enzyme-Linked Immunosorbent Assay, Protein Binding

ABSTRACT Importance: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality in patients with Systemic Lupus Erythematosus (SLE), due to both traditional CVD risk factors and SLE specific factors. Although statins are first-line therapy for primary prevention of CVD in the general population, it is unclear whether statins protect against first time cardiovascular events (CVEs) in patients with SLE. Objective: Determine whether statins are protective in primary prevention of CVEs among patients with SLE. Design, setting, and participants: This cohort study is a retrospective analysis of a well-characterized, prospective cohort of patients with SLE with patient follow-up beginning in 2013. Main outcome and measures: CVEs were defined as the occurrence of myocardial infarction, thrombotic stroke, onset of angina, or coronary bypass procedure. Statin use in the prior year was quantified based on standardized defined daily doses (DDD). Rates of occurrence were compared using pooled logistic regression. A multivariable model was performed to adjust for possible confounders. Results: The analysis was based on 8708 person-years of follow-up from 1396 cohort participants: 1283 (92%) were women, 567 (41%) Black, and 665 (48%) White. Patients were stratified by use of statin within the last year: none, < standard DDD, or [&ge;] standard DDD. The rate of events per 1000 person-years was respectively 5.3, 8.5, and 8.0 (p=0.31) within these 3 groups, suggesting potential lack of protective effect of statin treatment. The rates of CVEs among statin versus non-statin users remained the same after adjusting for and stratifying by total cholesterol level (p=0.18). Significantly higher rates of CVEs occurred among those with body mass index (BMI) 25-30 kg/m^2 (p=0.0066) and those prescribed [&ge;] 10 mg/day of prednisone (p=0.0003). Multivariable analysis also suggested a potential lack of protective effect of statins against CVEs (OR 1.48; 95% CI, 0.79-2.75; p=0.21883) and diabetes mellitus was found to be independently associated with an increased risk for development of CVEs (OR 4.48; 95% CI 1.99-10.08; p=0.00029). Conclusion and Relevance: Among patients with SLE, statin use may not be protective in primary prevention of CVEs, regardless of statin exposure. Prednisone use, history of diabetes mellitus, and elevated BMI were drivers of increased cardiovascular risk in univariate analysis. Diabetes mellitus persisted as an independent risk factor for CVEs in a multivariable model. Our work reinforces findings from clinical trials which have shown no reduction in subclinical measures of atherosclerosis with statin use among patients with SLE, as well as a mechanistic substudy which demonstrated that statins are ineffective in normalizing the pro-atherogenic changes induced by SLE.

Background: Real-world evidence evaluating the long-term effectiveness and safety of dimethyl fumarate (DMF) in relapsing-remitting multiple sclerosis (RRMS) remains limited, particularly in Middle Eastern populations. Furthermore, whether previous exposure to disease-modifying therapies influences longitudinal treatment response has not been adequately characterized. We evaluated the real-world effectiveness, safety, and temporal treatment dynamics of DMF in RRMS and compared outcomes between treatment-naive and previously treated patients. Methods: This longitudinal observational cohort study enrolled 120 adults with RRMS initiating DMF (TECRA (R)) at two multiple sclerosis centers in Iran. Clinical outcomes, magnetic resonance imaging (MRI) activity, disability progression, and adverse events were assessed over 18 months at 6-month intervals. Repeated Expanded Disability Status Scale (EDSS) measurements were analyzed using linear mixed-effects models, while relapse counts and MRI lesion activity were evaluated using generalized estimating equations. Prespecified subgroup analyses examined differences according to prior treatment status. Results: Ninety-five patients completed the study. DMF produced a marked suppression of disease activity, reducing the annualized relapse rate by 95% (1.56 {+/-} 0.93 to 0.08 {+/-} 0.24; P < 0.001). EDSS improved during the first year and remained near baseline after 18 months despite a modest increase during the final follow-up interval. MRI inflammatory activity declined significantly throughout follow-up, although a mild increase in gadolinium-enhancing lesions after 12 months suggested possible attenuation of treatment effect over time. Overall, 88.4% of patients remained relapse-free, 70.5% demonstrated no MRI disease activity, and 64.2% achieved no evidence of disease activity (NEDA-3). While overall clinical outcomes were comparable between treatment-naive and previously treated patients, longitudinal analyses revealed distinct temporal patterns of MRI activity between groups. DMF was well tolerated, with predominantly mild cutaneous and gastrointestinal adverse events and infrequent treatment discontinuation. Conclusions: In conclusion, DMF was well tolerated and effective in reducing clinical and radiological disease activity. These findings support the long-term effectiveness of DMF in routine clinical practice while highlighting the importance of continued clinical and radiological monitoring to optimize individualized treatment strategies.

Personalized neoantigen vaccines are an emerging strategy for cancer immunotherapy, but their effectiveness depends on selecting tumor-specific antigens capable of inducing functional T-cell responses. The VACINUS AI-informed neoantigen prioritization framework previously identified and peptide-validated three immunogenic Tier 1 neoantigens in the B16F10 melanoma model. In this study, we extended that framework by translating these validated neoantigens into a multi-epitope messenger RNA vaccine formulated with lipid nanoparticles and evaluating its preclinical immunogenicity and antitumor activity. The three VACINUS-prioritized B16F10 neoantigens were encoded within a single multi-epitope construct, BF-V1_27-Ser, and formulated to generate BF-RNA-P. In B16F10 tumor-bearing mice, BF-RNA-P induced neoantigen-specific CD8+T-cell responses, with the strongest response directed against the B16F10-1-4 epitope. Combination with anti-PD-1 further enhanced vaccine-induced CD44+IFN-{gamma}+ CD8+ T-cell activation, whereas anti-PD-1 alone did not induce detectable peptide-specific responses. BF-RNA-P also suppressed tumor growth in vivo, and combination treatment produced the strongest antitumor effect, reflected by reduced tumor volume and lower endpoint tumor burden. Together, these findings demonstrate that VACINUS-prioritized and peptide-validated neoantigens can be reformatted into a multi-epitope messenger RNA/lipid nanoparticle vaccine while retaining antigen-specific immunogenicity and antitumor activity. This study provides preclinical proof-of-concept for integrating AI-informed, TCR-aware neoantigen prioritization with messenger RNA/lipid nanoparticle delivery as a translational strategy for personalized cancer vaccine development.