Liem Binh Luong Nguyen

1. Seasonal influenza remains a major cause of morbidity and mortality worldwide, particularly among older adults [1]. Individuals aged 65 years account for a substantial proportion of influenza-a...

Background: OVX033 is a potential universal sarbecovirus vaccine candidate targeting the highly conserved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein. Preclinical studies have demonstrated cross-variant protection and favorable tolerability. This first-in-human trial evaluated the safety and immunogenicity of a single intramuscular dose of OVX033 in healthy adults (18–49 years). Methods: In this randomized, placebo-controlled, observer-blind, sequential, dose-escalation study, 48 participants, previously vaccinated with SARS-CoV-2 licensed vaccines, received either OVX033 (100 µg, 250 µg, or 500 µg; n = 12 per cohort) or placebo (n = 12, 4 per cohort). Solicited reactogenicity was recorded for 7 days, unsolicited adverse events (AEs) for 28 days, and serious AEs (SAEs) for 6 months. Immunogenicity assessments included anti-N immunoglobulin G (IgG) and N-specific T-cell responses. Results: OVX033 was safe and well-tolerated whatever the dose level. Injection site pain was the most common local reaction; fatigue, headache, and myalgia were the most frequent systemic symptoms. No severe reactogenicity, treatment-related SAEs, or safety signals were identified. OVX033 elicited a robust anamnestic anti-N IgG response, with titers peaking at day 29, and 4-fold rises versus baseline observed in 67%–100% of vaccinees. Modest increases of N-specific IFN-γ CD4+ T-cell responses were measured on days 8 and 29 after vaccination, while CD8+ T-cell responses remained below the limit of quantification. No clear OVX033 dose effect was evidenced. Conclusions: OVX033 demonstrated a favorable safety profile and strong boosting of preexisting N-specific humoral immunity. Although a N-specific T-cell–mediated immune response was achieved, it remained of limited amplitude. This limitation could be addressed by implementing a 2-dose regimen, or through the adjuvantation of the vaccine. Clinical Trials Registration: NCT06128382; EU-CT 2023-506396-94-00.

Streptococcus pneumoniae causes invasive pneumococcal disease and pneumonia. This study models the burden of adult pneumococcal disease in France. Over a 5-year period, approximately 630,000 cases and €3.1 billion of costs were attributable to pneumococcus, mostly non-invasive disease, with nearly 80% due to serotypes included in 20-valent pneumococcal conjugate vaccine.

Background: The immunopathogenesis of clade IIb monkeypox virus (MPXV) infection and its relationship with clinical severity remain poorly defined. We characterized cytokine responses in acute and convalescent mpox to delineate inflammatory profiles. Methods: In a multicenter cohort, we quantified 45 plasma protein biomarkers in 3 adult groups: acute mpox (polymerase chain reaction–confirmed clade IIb MPXV infection sampled 30 days postinfection); and uninfected controls matched for age, sex, race, and HIV status. Biomarkers spanned innate and adaptive immune activation, systemic inflammation, and tissue repair. Principal component analysis and unsupervised hierarchical clustering defined immune profiles. Associations with clinical features were explored via logistic regression. Results: Sixteen participants with acute mpox (median [IQR], 6 days [4–8] from symptom onset; 13% vaccinated) were compared with 16 controls. Three immune clusters were identified. Cluster 1 comprised only unvaccinated acute mpox and exhibited a broad inflammatory signature (IFN-γ, CXCL9/10/11, CCL 7/8, IL-6/10, OSM). Cluster 2 displayed elevated TNFSF12 and FLT3LG, suggestive of tissue remodeling. Cluster 3 demonstrated lower cytokine expression. Mucosal involvement was associated with the inflammatory cluster 1 (odds ratio, 7.85; 95% CI, 1.02–102.40; P = .048). Among 25 participants who were convalescent (median [IQR], 405 days [225–450] postinfection; 12% vaccinated), clustering did not distinguish cases from controls. However, targeted comparisons demonstrated persistent low-grade immune activation (IL-6, OSM) and tissue-remodeling signatures (TGF-α, VEGF-A). Conclusions: Acute clade IIb mpox displays distinct inflammatory profiles, with systemic inflammation concentrated among those with mucosal disease. Convalescence shows partial resolution but persistent tissue repair activity. These pathways may support risk stratification and targeted therapeutic interventions.

Streptococcus pneumoniae causes invasive pneumococcal disease and pneumonia. This study models the burden of adult pneumococcal disease in France. Over a 5-year period, approximately 630,000 cases and €3.1 billion of costs were attributable to pneumococcus, mostly non-invasive disease, with nearly 80% due to serotypes included in 20-valent pneumococcal conjugate vaccine.

Médecin Sans Frontière (MSF) intervient depuis les années 1980 à Ndhiwa, un sous-comté du Sud-Ouest du Kenya, où sévit une épidémie généralisée de VIH, avec une prévalence à 24% et une incidence à 2,2/100 personnes année (PA). Conformément aux objectifs de l’ONUSIDA 90-90-90, puis 95-95-95, MSF a décidé de mettre en place différentes interventions pour diminuer l’incidence de l’infection par le VIH. Dans un premier temps, nous avons développé un modèle mathématique de la transmission et de l’histoire naturelle de l’infection par le VIH à Ndhiwa afin d’étudier l’efficacité et le coût efficacité de trois niveaux d’interventions sur le continuum de soin. Nous avons ainsi estimé qu’en maintenant l’offre de soins à son niveau actuel, sans intervention, l’incidence de l’infection par le VIH diminuerait à 1,51/100 PA en 2032, tandis que seules les interventions de rétention et la combinaison de toutes les stratégies faisaient baisser l’incidence respectivement à 1,03/100 PA et 0,75/100 PA. Comparé au standard de soins, la stratégie de rétention avait un rapport incrémental de coût-efficacité de 130€/année de vie gagnée (AVG) tandis que La combinaison des interventions atteint un ICER de 370€/AVG. Dans un deuxième temps, nous avons modélisé l’efficacité d’une intervention qui améliorerait le continuum de soin de 90-90-90 à 95-95-95, comparée à une intervention qui implémenterait une prophylaxie pré-exposition (PrEP) sur une population à haut risque avec un taux de couverture de 10%. Nous estimons que dans une épidémie généralisée où le continuum de soin atteint 90-90-90, l’amélioration du continuum de soin à 95-95-95 est plus efficace que la PrEP pour diminuer l’incidence de l’infection par le VIH En conclusion, les résultats de notre travail soulignent les effets synergiques e très coût-efficace d’interventions multimodales sur le continuum de soin, et leur rôle important aussi important que la PrEP pour diminuer l’incidence de l’infection par le VIH.

Introduction: Individuals living with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited. Methods: The AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022–March 2023) with 6 months of follow-up. Adults with BMI ≥35 kg/m² were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs ≥50 years), and BMI (<40 vs ≥40 kg/m²). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for four influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed. Results: A total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m². At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1–2.3), A/H3N2 (2.0; 95% CI, 1.3–3.2), and B/Yamagata (1.3; 95% CI, 1.0–1.8), but not for B/Victoria (0.9; 95% CI, 0.6–1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups. Conclusion: In adults living with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population