Infectious Disease Models and Innovative Therapies

In September 2023, a measles outbreak occurred in a middle school (Rhône valley, France), with the index case returning from Asia. Investigations involved case validation, virological analyses, contact tracing and checking vaccination records to determine measles vaccination coverage (VC) and attack rates (AR). Among 643 students, 49 measles cases occurred between 6 September and 18 October 2023 (AR = 7.6%). Two-dose vaccination coverage was 93.5% (601/643). Virological analyses confirmed the measles strains’ clonality (genotype D8) and the imported origin. Concordance between health record vaccination status and immunological profile was established for 27 cases. In a sub-cohort of children (all cases and 309 non-cases), AR was 100% in unvaccinated children, and 43.7%, 16.5% and 3.2% among two-dose vaccinated children with the first dose administered at 6–8, 9–11 and ≥ 12 months, respectively. After multivariate binomial regression, vaccine effectiveness (VE) was 96.4% (95% confidence interval (CI): 91.4–98.5) after two-dose vaccination with the first dose at ≥ 12 months, confirming long-term effectiveness of measles-mumps-rubella vaccines. When the first dose was given at 9–11 and 6–8 months, respectively, VE was 83.3% (95% CI: 74.3–89.2) and 60.7% (95% CI: 10.6–82.7). This measles epidemic mainly affected unvaccinated or two-dose vaccinated children with first dose administered before age 12 months.

Abstract ID2 expression is typically associated with promoting effector differentiation in CD8⁺ T cells. Here, we show that ID2 upregulation instead characterizes the optimal memory CD8⁺ T cell response in individuals who naturally maintain durable control of HIV-1 without therapy. We further identify a subset of memory CD8+ T cells co-expressing the transcription regulators TCF1 and ID2 that combine stemness with broad effector functions. These TCF1+ID2+ cells exhibit high proliferative capacity, robust cytokine production, and restrained expression of exhaustion markers, enabling sustained responses upon repeated antigen stimulation. They constitute the predominant virus-specific memory CD8+ T cell population in naturally controlled CMV, HIV-1, and SIV infections. Our findings reveal a poised memory state that balances effector and survival programs, suggesting that TCF1+ID2+ memory CD8+ T cells play a central role in maintaining durable antiviral immunity during persistent infections.

Yersinia pestis has spilled over from wild rodent reservoirs to commensal rodents and humans, causing three historically recorded pandemics. Depletion in the copy number of the plasmid-encoded virulence gene pla occurred in later-dated strains of the first and second pandemics, yet the biological relevance of the pla deletion has been difficult to test. We identified modern Y. pestis strains that independently acquired the same pla depletion as ancient strains and herein show that excision of pla from the multicopy pPCP1 plasmid is accompanied by the integration of a separate full pPCP1 harboring pla into the single-copy pCD1 plasmid, reducing pla dosage. Moreover, we demonstrate that this depletion decreases the mortality of mice in models of bubonic plague but not in the pneumonic and septicemic forms of the disease. We hypothesize that pla depletion may have been selectively advantageous in bubonic plague, owing to rodent fragmentation after pandemic-induced mortality.

We report the complete genome sequences of two valuable strains to investigate plague pathogenesis: (i) Yersinia pestis strain 6/69, which was isolated from a bubonic plague patient in Madagascar and contains pCD1, pMT1, and pPCP1 virulence plasmids, and (ii) the 6/69 strain cured of pPCP1.

ABSTRACTThe journey of early‐career researchers (ECRs) in immunology is marked by many challenges but also exciting prospects. Here we bring a snapshot of the recent ECR workshop organized by the Young European Federation of Immunology Societies (yEFIS) during the 7th European Congress of Immunology (ECI), which took place in Dublin Ireland from September 1 to 4, 2024. This article brings forward the unique experiences and perspectives of eight Principal Investigators (PIs) and the events that shaped their careers in immunology. Navigating challenges, from mastering intricate laboratory techniques, securing tenure, or moving countries, to finding the right balance between family and research life; their stories reveal the diverse paths to independence within academia. This series celebrates scientific accomplishments acknowledging the non‐linearity of career paths and the value of passion for discovery, self‐confidence, resilience, and perseverance in their academic journeys.

Purpose Airborne pathogen scan penetrate in human respiratory tract and can cause illness. The use of animal models to predict aerosol deposition and study respiratory disease pathophysiology is therefore important for research and a prerequisite to test and study the mechanism of action of treatment. NHPs are relevant animal species for inhalation studies because of their similarities with humans in terms of anatomical structure, respiratory parameters and immune system. Materials and methods The aim of this review is to provide an overview of the state of the art of pathogen aerosol studies performed in non-human primates (NHPs). Herein, we present and discuss the deposition of aerosolized bacteria and viruses. In this review, we present important advantages of using NHPs as model for inhalation studies. Results We demonstrate that deposition in the respiratory tract is not only a function of aerosol size but also the technique of administration influences the biological activity and site of aerosol deposition. Finally, we observe an influence of a region of pathogen deposition in the respiratory tract on the development of the pathophysiological effect in NHPs. Conclusion The wide range of methods used for the delivery of pathogento NHP respiratory airways is associated with varying doses and deposition profiles in the airways.

BackgroundEarly pregnancy Zika virus (ZIKV) infection is associated with major brain damage in fetuses, leading to microcephaly in 0.6–5.0% of cases, but the underlying mechanisms remain largely unknown.MethodsTo understand the kinetics of ZIKV infection during fetal development in a nonhuman primate model, four cynomolgus macaque fetuses were exposed in utero through echo-guided intramuscular inoculation with 103 PFU of ZIKV at 70–80 days of gestation, 2 controls were mock inoculated. Clinical, immuno-virological and ultrasound imaging follow-ups of the mother/fetus pairs were performed until autopsy after cesarean section 1 or 2 months after exposure (n = 3 per group).ResultsZIKV was transmitted from the fetus to the mother and then replicate in the peripheral blood of the mother from week 1 to 4 postexposure. Infected fetal brains tended to be smaller than those of controls, but not the femur lengths. High level of viral RNA ws found after the first month in brain tissues and placenta. Thereafter, there was partial control of the virus in the fetus, resulting in a decreased number of infected tissue sections and a decreased viral load. Immune cellular and humoral responses were effectively induced.ConclusionsZIKV infection during the second trimester of gestation induces short-term brain injury, and although viral genomes persist in tissues, most of the virus is cleared before delivery.