赛诺菲巴斯德

Introduction Influenza A virus poses ongoing global health and economic challenges due to its antigenic variability and pandemic potential. Current seasonal vaccines targeting the variable hemagglutinin (HA) provide limited and strain-specific protection. The conserved Matrix 2 Ectodomain (M2e) offers a promising universal vaccine target, eliciting protection by targeting infected cells rather than neutralizing virions. However, the mechanism underlying protection mediated by this simple antigen is complex, and no M2e-based vaccine has been licensed yet.Area Covered Precise M2e-vaccine optimization is needed. This review provides in-depth description of M2e established knowledge, as well as comparative studies using M2e-based vaccines. From this, the ‘ideal archetype’ of a universal vaccine including M2e will be defined. Finally, a review of the current preclinical nanoparticle based M2e vaccine will be provided, described, and analyzed.Expert opinion Optimizing antigen presentation, evaluating Fc-mediated effector functions with standardized assays, and integrating M2e into multivalent nanoparticle platforms targeting complementary conserved antigens are likely to be key steps toward achieving broad, durable, and clinically translatable protection.

Establishment of diagnostic biomarkers of previous disease exposure is essential in precision medicine. One of the challenges in this application is associated with the certainty of the cases being either positive or negative in the training and test analysis sets used to establish a reliable cutoff. Practical situations like asymptomatic cases, non-reported records, absence of doctors' visits, missing biomarker samples, or lack of assay sensitivity at the time of testing may result in subjects being misclassified as negative cases. The uncertain response labels subsequently lead to a biased cutoff value determination since the main assumption of supervised classification methods is that the labels of training and test samples are true with random errors. This paper provides statistical solutions to address the unknown potential labeling issue focusing on two practical aspects: 1. Statistical visualization methods to explore sample responses and so identifying potential mislabeled cases; 2. Application of a semi-supervised learning method, Robust Mixture Discriminant Analysis (RMDA), to responses with uncertain labels for determination of cutoff value; These topics are illustrated using real pediatric serum IgA biomarker dataset for identification of RSV previous exposure status.

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection (LRTI) and hospitalizations in United States (US) infants and young children. Following ACIP’s recommendation for nirsevimab in infants up to 8 months, we conducted a systematic literature review (SLR) to describe RSV and LRTI epidemiology in US children aged ≥8 months to < 5 years across healthcare settings.Figure 1PRISMA Flow Diagram This SLR followed PRISMA guidelines and was pre-registered on PROSPERO (#CRD42024599190). Literature published from 2009-2024 were evaluated for outcomes including RSV and LRTI rates in outpatient, urgent care, or emergency department (ED); RSV and LRTI hospitalization rates; and RSV laboratory testing practice and patterns. This review identified 2085 records; based on the eligibility criteria, 101 studies were included (Figure 1). Of the 101 studies, 34 were prospective cohort, 62 were retrospective cohort, and the remaining 5 were of other designs (1 trial, 1 case-control, 3 cross-sectional surveys). 35 studies provided national-level data; 64 were on various states; 2 were of unknown geographical location. All rate numbers were heterogeneous. 8 studies reported rates in the outpatient or ED settings. In urgent care, no data were available. RSV/LRTI outpatient rates ranged 1.5 to 277.8 per 1000. In the ED, the rates ranged 10 to 84.6 per 1000. RSV hospitalization rates were reported in 26 studies, and the rates were highly variable. RSV laboratory testing patterns were reported in 7 studies with only 1 study providing outpatient data. Though limited, underestimation of RSV is indicated in the outpatient compared to the inpatient setting (testing rates: 69-77% vs. 70-100%, respectively). This systematic review underscores the significant impact of RSV in US children 8 months through < 5 years of age in all healthcare settings. No data are available for urgent care, and data from outpatient and ED settings remain limited while hospital data are variable. Inconsistent testing and reporting practices may be contributing factors. Given the variable disease burden estimates, additional studies are essential to assess healthcare utilization and impacts in this population. Mina Suh, MPH, International Health, Moderna: Grant/Research Support|Sanofi: Grant/Research Support|Sobi: Grant/Research Support Naimisha Movva, MPH,Chronic Disease Epidemiology & Regulatory Affairs, Moderna: Grant/Research Support|Sanofi: Grant/Research Support Ruvim Izikson, MD, MPH, Sanofi: Stocks/Bonds (Public Company) William V. La Via, MD, AstraZeneca: Stocks/Bonds (Public Company)|Sanofi: Employee|Sanofi: Stocks/Bonds (Public Company) Susan T. Pastula, MPH, Moderna: Grant/Research Support|Sanofi: Grant/Research Support Marina Amaral de Avila Machado, PhD, Sanofi: Stocks/Bonds (Private Company) Thomas Shin, MA, MPH, Sanofi: Employee of Sanofi|Sanofi: employee and may hold stock or stock options Christopher Rizzo, MD, Sanofi: Employee

Background The COVID-19 Prevention Network (CoVPN) co-conducted six COVID-19 phase 3 vaccine efficacy (VE) trials that featured harmonized immunogenicity analyses using validated antibody assays. These trials enabled a uniquely comprehensive characterization of immunogenicity produced by different vaccine platforms and regimens in individuals with and without prior SARS-CoV-2 acquisition. Methods Comparisons of serum binding antibody concentration and serum neutralization antibody ID50 titers were performed across three strata: vaccine immunity (vaccination in SARS-CoV-2-naïve individuals), natural immunity (placebo with prior SARS-CoV-2 acquisition), and hybrid immunity (vaccination after prior SARS-CoV-2 acquisition). We compared immunogenicity across immunity strata for each trial and each dose, adjusting for age, sex assigned at birth, and body mass index. Antibody levels were also examined in relation to VE. Results Antibody levels in response to a single vaccine dose varied across trials and generally increased most substantially after a second dose in naïve participants. Fold rise in antibody levels after a single dose were more pronounced in participants with hybrid immunity: a single dose of any of the tested vaccine yielded responses comparable to or exceeding the post-dose-two (peak) response of any two-dose vaccine in naïve participants. Population-level antibody levels demonstrated high concordance with VE across trials and immunity strata. Conclusions In SARS-CoV-2-naïve individuals, a two-dose vaccine regimen is needed to provide antibody levels correlated with protection against disease caused by the cognate virus strain. In contrast, in individuals with prior SARS-CoV-2 acquisition, a single dose of any of the tested vaccines/platforms (mRNA/protein/vector) provides comparably high antibody levels.

mRNA delivery using lipid nanoparticles (LNPs) has become a cornerstone of modern biological therapeutics. During the formulation of LNPs, uniform mixing of LNP components is critical to ensuring desirable functional properties. This study employs simple bi-directional T-mixing of lipids in ethanol with mRNA in buffer to evaluate the effects of mixing chamber turbulence on mRNA-LNP biophysical attributes and develops a mechanistic model relating the mixing processes to biological performance. LNPs encapsulating hEPO mRNA formulated under turbulent mixing conditions with ionizable lipid OF-02 demonstrate higher hEPO expression than those formulated under laminar mixing conditions via two routes of administration in an in vivo mouse model. By measuring LNP zeta potential, fusogenicity, and lipid fluidity as functions of pH, we propose a hypothetical model for increased pH-sensitivity of the turbulently formulated LNPs, presumably resulting in improved intracellular release of mRNA. Unique profiles measured by small-angle X-ray scattering (SAXS) and greater homogeneity observed by cryo-TEM for LNPs formulated under turbulent mixing conditions further support this model. Increased serum protein binding for these turbulently mixed mRNA-LNPs suggests an additional mode of action involving receptor-mediated uptake following systemic delivery. A follow-up study with LNPs made with reduced lipid : mRNA mass ratios indicates that turbulent mixing may preserve LNP function with lower lipid load, compared to LNPs made with higher lipid load under laminar flow conditions. Altogether, these findings underscore important connections between LNP performance and formulation process, offering valuable insights for optimization of mRNA-LNP formulations.