influenza vaccine (Agriflu / eTIV_a / Begripal)

Immunogenicity and Protective Efficacy of a Trivalent Whole-Virion Inactivated SARS-CoV-2 Vaccine Against Vaccine-Matched Ancestral, Delta, and Omicron BA.5 Variants in K18-hACE2 Mice.

Yetiskin Hazel H, Uygut Muhammet Ali MA, Pavel Shaikh Terkis Islam STI, Kaplan Busra B et al.

Continuous antigenic evolution of SARS-CoV-2 has reduced the effectiveness of vaccines based on a single ancestral strain, highlighting the need for multivalent vaccine strategies. We developed a trivalent whole-virion inactivated vaccine containing ancestral (ERAGEM), Delta, and Omicron BA.5 antigens and evaluated its immunogenicity and protective efficacy in K18-hACE2 transgenic mice. β-propiolactone-inactivated ERAGEM, Delta, and Omicron BA.5 antigens were combined at 1 µg each (3 µg total) with aluminium hydroxide and administered intraperitoneally on days 0 and 21. Variant-specific binding and neutralizing antibody responses were assessed by enzyme-linked immunosorbent assay (ELISA) and microneutralization assays. On day 42, mice were challenged with ERAGEM, Delta, or Omicron BA.5. Survival, body weight, body temperature, infectious viral titers, and viral RNA loads were evaluated. The trivalent vaccine induced binding and neutralizing antibodies against all three vaccine components, and titers rose after the booster dose. Neutralizing responses were highest against the BA.5 component. Vaccinated mice showed 100% survival following challenge with each vaccine-matched variant and maintained stable body weight and temperature throughout the observation period. Unvaccinated controls challenged with Omicron BA.5 showed no mortality, so protection against this component could be assessed only virologically. No infectious virus was detected in the lungs of vaccinated animals, while viral titers and RNA loads in the nasal turbinates were significantly reduced compared with unvaccinated controls. A trivalent whole-virion inactivated SARS-CoV-2 vaccine containing ancestral, Delta, and Omicron BA.5 antigens elicited variant-specific humoral immunity and protected mice against challenge with each vaccine-matched component: against lethal challenge for the ancestral and Delta components, and against viral burden for Omicron BA.5, which was not lethal in unvaccinated controls. These outcomes were obtained at a lower per-antigen dose than in our previously reported monovalent and bivalent formulations; because those were independent studies rather than contemporaneous comparators, this suggests a dose-sparing potential that warrants formal evaluation rather than demonstrating one. Cross-protection against variants not included in the formulation was not assessed.

Transdermal Delivery of an Adjuvanted SARS-CoV-2 Triple RBD Subunit Vaccine in Mice Using Dissolving Microneedle Array Patch.

Kim Eun E, Lee Moon-Su MS, Khan Muhammad S MS, Huang Shaohua S et al.

Background: The continuous emergence of antigenically distinct SARS-CoV-2 variants of concern (VOCs) necessitates the development of versatile and effective vaccine platforms capable of inducing broad and sustained immunity. Methods: We designed a chimeric trivalent recombinant protein, TriRBD, incorporating the receptor-binding domains (RBDs) of the Delta, Omicron BA.1, and XBB.1 subvariants. To enhance delivery efficiency and immunogenicity, TriRBD was formulated into a dissolving hyaluronic-acid-based microneedle array patch (MAP) using the droplet extension (DEN) technique. We investigated the synergistic effects of two squalene-based oil-in-water (O/W) emulsions, SqTS (Squalene/Tween-80/Span-85) and SqT (Squalene/Tween-80), as adjuvants within the MAP after gamma-irradiation sterilization, alongside safety evaluations via rabbit skin tests. Results: The SqTS-adjuvanted MAP formulation was found to be non-irritating. Immunogenicity studies in BALB/c mice revealed that MAP-delivered TriRBD elicited significantly higher and more durable IgG endpoint titers (EPT) compared to intramuscular injection, with robust antibody levels sustained for up to 52 weeks. Notably, the irradiated SqT-adjuvanted MAP group exhibited a highly balanced Th2/Th1 immune response (IgG1/IgG2a ratio), while the irradiated SqTS-adjuvanted MAP group shifted toward a Th2-preferred against TriRBD. Although the EPT against the Omicron BA.1 variant was relatively lower, the irradiated MAP-SqT-TriRBD group elicited significantly both of IgG1 and IgG2a, resulting in a balanced and broadened antibody repertoire. Conclusions: These findings demonstrate that combining a trivalent RBD antigen with a SqT-adjuvanted MAP platform provides a potent, safe, and thermostable strategy for broad-spectrum protection against evolving SARS-CoV-2 variants and future pandemic threats.

Optimization of Environmental Sampling Methods for the Detection of Virus Contamination in a Layer Chicken Farm: A Pilot Study Using Postvaccination Monitoring.

Lee Sun-Hak SH, Choi Yun-Jeong YJ, Choi Chi-Hoon CH, Cho Andrew Y AY et al.

Environmental testing of poultry farms after an outbreak of infectious viral disease such as infectious bronchitis or avian influenza is essential for verifying viral clearance and supporting the safe resumption of operations. To find optimal sampling locations inside and outside of chicken farms, a laboratory study simulating a respiratory virus-infected poultry house with wire layer cages was conducted using a commercial live attenuated infectious bronchitis virus vaccine as a surrogate virus administered to 21-day-old layer chickens. Oropharyngeal swab samples of chickens, air, and four locations within the poultry house, including manure conveyor belt, floor surface, environmental dust, and on-farm boots, were evaluated on the day before and 1, 3, 5, and 8 days after spray vaccination. Tools that were used outside the poultry house, such as off-farm shoes, farm work clothes, protective face masks, cotton gloves, egg transport vehicles, and egg transport pallets, were also evaluated. Due to inherent differences in environmental conditions and facility structures across farms, environmental sampling was performed following a standardized protocol designed in this study to ensure consistency across all collection sites. Virus loads at each sampling site were determined by quantitative real-time reverse transcription PCR and expressed as 50% egg infectious dose (EID50) equivalents. In addition, a subset of samples was further subjected to virus re-isolation through egg inoculation. The highest viral RNA loads inside and outside of the farm were observed from the manure conveyer belts and off-farm shoes, respectively. Samples taken from floor surfaces and on-farm boots also consistently showed high amounts of viral RNA. While infectious viruses were successfully re-isolated from several internal samples, no infectious virus was detected in samples collected outside the farm, suggesting that no viral spillover occurred under the experimental conditions. Our findings identified high-risk virus accumulation sites within poultry farms and highlight the utility of optimized, standardized environmental sampling protocols in enhancing detection sensitivity and supporting effective risk-based surveillance.

Influenza Vaccine Effectiveness Across Nutritional Status Categories in Patients Hospitalized With Acute Heart Failure: A Secondary Analysis of the PANDA II Trial.

Liu Xinru X, Wang Zhiyan Z, Hua Chang C, Wu Yanfang Y et al.