pneumococcal vaccine (Prevenar20 / PCV20 / PF 06482077)

Pneumococcal meningitis secondary to chronic orbital inflammation with skull base erosion: a case report.

Tie Xinghua X, Sun Xiaoman X

This case report describes a 32-year-old female patient who developed acute pneumococcal meningitis following six-year chronic orbital inflammatory changes after strabismus corrective surgery. The patient experienced gradual deterioration of right-eye vision and recurrent retro-orbital headache; serial magnetic resonance imaging (MRI) from 2021 to 2023 demonstrated diffuse intraconal retrobulbar abnormalities and extraocular-muscle thickening. She subsequently presented with high fever, generalized seizures and impaired consciousness. Cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) detected Streptococcus pneumoniae and low-abundance Epstein-Barr virus (EBV) DNA; Active EBV-associated central nervous system infection could not be confirmed in the absence of CSF quantitative EBV polymerase chain reaction (PCR), EBV serology and immune-status testing. The patient received broad-spectrum intravenous antimicrobial, antiviral and glucocorticoid therapy, followed by endoscopic endonasal resection of inflammatory lesions at the ethmoid-skull-base complex. Histopathological examination of surgical specimens revealed non-specific inflammatory granulation tissue, and Langerhans cell histiocytosis was excluded. At six-month follow-up, the patient remained seizure-free; infectious foci showed near-complete resolution on imaging, yet mild residual orbital-leptomeningeal abnormalities persisted with modest visual improvement. This case demonstrates the potential for delayed intracranial extension from long-standing chronic orbital inflammation and highlights both the diagnostic utility and interpretive limitations of CSF-mNGS in clinical practice.

Immunogenicity and protective efficacy of recombinant BCG expressing a multi-epitope vaccine against mycobacterium tuberculosis.

Zhang Xuan-Ji XJ, Luo Jia-Rui JR, Tian Ting-Ting TT, Shi Juan J et al.

Mycobacterium tuberculosis (Mtb) infects approximately one-quarter of the global population, of whom 5%-10% develop active tuberculosis (TB). Although Bacillus Calmette-Guérin (BCG) remains the cornerstone vaccine against severe infant TB, its efficacy in adults is limited, underscoring the need for novel TB vaccines. This study aimed to design a multi-epitope vaccine, tMEV, and validate its protective potential through bioinformatic prediction and in vivo experiments. tMEV was constructed from dominant T- and B-cell epitopes derived from Mtb ESAT-6, PE35, PPE38, and PE4 proteins, fused with an adjuvant. Its vaccine candidacy was assessed via physicochemical and solubility profiling, secondary and tertiary structure modeling, TLR-4 molecular docking, molecular dynamics simulation, and immune simulation. The tMEV coding sequence was cloned into pMV361 and transformed into BCG to generate recombinant BCG (rBCG-tMEV). Immunogenicity, antigenicity, and protective efficacy were evaluated in mouse immunization and Mtb challenge models. tMEV exhibited favorable vaccine-like properties in silico. In mice, both tMEV and rBCG-tMEV induced Mtb-specific immune responses. Compared with PBS, tMEV significantly enhanced cellular and humoral immunity with a Th2-biased profile. Relative to conventional BCG, rBCG-tMEV elicited a superior mixed Th1-Th2 response and higher antigen-specific immunity, accompanied by increased secretion of IFN-γ, IL-2, TNF-α, granzyme B, and perforin. Moreover, rBCG-tMEV markedly reduced bacterial loads in the lungs and spleens of Mtb-infected mice, conferring partial protection. These findings demonstrate that tMEV and rBCG-tMEV possess robust immunogenicity and protective potential against Mtb, representing promising novel TB vaccine candidates and providing a rationale for future vaccine development and optimization.

Correction to "Screening Natural Cholesterol Analogs to Assemble Self-Adjuvant Lipid Nanoparticles for Antigens Tagging Guided Therapeutic Tumor Vaccine".

A Phase 1/2 Trial Evaluating the Safety and Immunogenicity of an mRNA-based Seasonal Influenza Vaccine Candidate Encoding Hemagglutinin and Neuraminidase.

De Coster Ilse I, Cardona Jose F JF, Ferguson Murdo M, Leroux-Roels Isabel I et al.

Hemagglutinin (HA) is the principal immunologic target of most licensed seasonal influenza vaccines. Targeting both HA and neuraminidase (NA) might improve vaccine effectiveness. This randomized phase 1/2 study evaluated an investigational mRNA-based quadrivalent seasonal influenza vaccine, encoding HA and NA of A/H1N1, A/H3N2, B/Victoria, and B/Yamagata (FLUm4HA-4NA). In phase 1, adults aged 18-50 years received either one of twelve mRNA vaccine formulations of varying HA-only or HA and NA mRNA doses, or a licensed quadrivalent seasonal influenza comparator. In phase 2, participants aged 18-64 years (younger adults) and 65-85 years (older adults) received FLUm4HA-4NA (three groups per age category, with different HA/NA mRNA doses) or age-appropriate licensed quadrivalent comparator. Primary endpoints were safety/reactogenicity, and hemagglutination inhibition [HI] and NA inhibition [NI] responses against the four seasonal strains at day 29. Cross-reactive HI/NI responses against drifted strains, virus neutralization, and HA-/NA-specific cell-mediated immunity were evaluated in phase 2 as tertiary objectives. A total of 293 participants (21-25 per group) were vaccinated in phase 1, 480 younger (108-137 per group) and 483 older adults (117-125 per group) in phase 2. Solicited events were more frequent with FLUm4HA-4NA than comparators and were mostly short-lived and mild or moderate. No deaths or vaccine-related serious adverse events were reported. Post-vaccination HI and neutralizing titers in the FLUm4HA-4NA groups were similar or higher for the A strains and lower for the B strains versus comparators. NI responses exceeded those of comparators for all four strains. HI and NI titers against evaluated drifted A strains were similar or higher after FLUm4HA-4NA than after comparator vaccination. HA-specific CD4+ and CD8+ T-cell responses were generally higher after FLUm4HA-4NA than comparator vaccination. FLUm4HA-4NA showed an acceptable safety profile and humoral and cellular immunogenicity in the study population, supporting further development and formulation optimization to improve influenza B HI responses. ClinicalTrials.gov: NCT05823974; euclinicaltrials.eu: 2022-502308-66-00.