MMR + varicella zoster vaccine (MMRV zoster vaccine)

Lampricide 3-trifluoromethyl-4-nitrophenol (TFM) impacts whole-organism oxygen consumption in non-target fishes.

Göbel Melina M, Moore Aiden A, Hafenbrak Tabitha T, Lennox Robert R et al.

The application of the lampricide TFM (3-trifluoromethyl-4-nitrophenol) to streams infested with larval sea lamprey constitutes the backbone of the Sea Lamprey Control Program in the Laurentian Great Lakes, but native species have greatly varying sensitivities to TFM. Earlier work by D'Souza and colleagues revealed that the whole-animal oxygen consumption of larval sea lamprey responded in a dose-dependent manner to increasing TFM concentrations. We set out to determine 1) if TFM exposure leads to stepwise increases in whole-animal oxygen consumption in non-target fishes, and 2) if exposure to lethal TFM concentrations leads to increases in oxygen consumption comparable to the animals' Maximum Metabolic Rate (MMR). Using intermittent-flow respirometry, we tested three non-target fish species with known varying TFM sensitivity: young-of-the-year lake sturgeon (sensitive), juvenile rainbow trout (intermediate), and juvenile smallmouth bass (resistant). We confirmed that all three species exhibit increases in oxygen consumption during exposure to increasing concentrations of TFM, but found that the relationship between MMR and oxygen consumption prior to death during lethal TFM exposure is complex and species-dependent. While this complex relationship broadens the need for species-specific testing, it opens up interesting possibilities both for (1) in-situ testing, e.g., through the deployment of river-side field respirometry systems to monitor real-time responses of both target and non-target species to TFM treatments, and (2) ex-situ testing, e.g., through the establishment of less-lethal assays to determine TFM sensitivity under various species × temperature × water chemistry combinations.

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.