Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have constituted a public health issue with drastic mortality higher than 34%, necessitating the development of an effective vaccine. During MERS-CoV infection, the trimeric spike protein on the viral envelope is primarily responsible for attachment to host cellular receptor, dipeptidyl peptidase 4 (DPP4). With the goal of generating a protein-based prophylactic, we designed a subunit vaccine comprising the recombinant S1 protein with a trimerization motif (S1-Fd) and examined its immunogenicity and protective immune responses in combination with various adjuvants. We found that sera from immunized wild-type and human DPP4 transgenic mice contained S1-specific antibodies that can neutralize MERS-CoV infection in susceptible cells. Vaccination with S1-Fd protein in combined with a saponin-based QS-21 adjuvant provided long-term humoral as well as cellular immunity in mice. Our findings highlight the significance of the trimeric S1 protein in the development of MERS-CoV vaccines and offer a suitable adjuvant, QS-21, to induce robust and prolonged memory T cell response.

Objectives. The aim of this study was to investigate the auditory and vestibular consequences of congenital cytomegalovirus (cCMV) infection in a C57BL/6 mouse model. This model, established via intraperitoneal inoculation, was designed to mimic clinical phenotypes.Methods. A cCMV infection model was developed by intraperitoneally inoculating C57BL/6 mice with murine cytomegalovirus. Auditory and vestibular functions were evaluated using auditory brainstem response tests, as well as open field, swim, and rotarod assessments. Histologic analysis of the inner ear was also conducted.Results. The study successfully established a cCMV infection model in C57BL/6 mice. Auditory deficits of varying severity and laterality were observed, mirroring the clinical spectrum seen in humans. In contrast, vestibular function was minimally affected and did not correlate with auditory deficits. Histopathologic examination revealed predominant damage to spiral ganglion neurons, while the vestibular organs remained relatively intact.Conclusion. Our optimized mouse model effectively recapitulates the inner ear manifestations of human cCMV infection. The predominance of auditory over vestibular deficits provides valuable insights for developing targeted therapeutic interventions for cCMV-related inner ear sequelae.

Recessive variants of SLC26A4 are a common cause of hereditary hearing impairment and are responsible for non-syndromic enlarged vestibular aqueducts and Pendred syndrome. Patients with bi-allelic SLC26A4 variants often suffer from fluctuating hearing loss and recurrent vertigo, ultimately leading to severe to profound hearing impairment. However, there are currently no satisfactory prevention or treatment options for this condition. The CRISPR/Cas9 genome-editing technique is a well-known tool for correcting point mutations or manipulating genes and shows potential therapeutic applications for hereditary disorders. In this study, we used the homology-independent targeted integration (HITI) strategy to correct the SLC26A4 c.919-2A>G variant, the most common SLC26A4 variant in the Han Chinese population. Next-generation sequencing was performed to evaluate the editing efficiency of the HITI strategy. The results showed that only 0.15% of the reads successfully exhibited HITI integration, indicating that the c.919-2 region may not be a suitable region for HITI selection. This suggests that other site selection or insertion strategies may be needed to improve the efficiency of correcting the SLC26A4 c.919-2A>G variant. This experience may serve as a valuable reference for other researchers considering CRISPR target design in this region.

Background: Otitis media with effusion (OME) is a widespread condition that causes hearing impairment, particularly in pediatric populations. Existing non-absorbable tubes often require elective or unplanned removal surgery. Bioabsorbable polylactic acid (PLA) offers a promising alternative due to its inherent biocompatibility and tunable degradation characteristics. In this study, we designed, fabricated, and comprehensively evaluated a novel PLA middle-ear ventilation tube. Methods: Bioabsorbable PLA tubes were designed and fabricated based on commercial models. In vitro biocompatibility was assessed according to ISO 10993 guidelines. A guinea pig model was used to perform in vivo evaluations, including otoscopic examinations, auditory brainstem response (ABR) measurements, micro-computed tomography (micro-CT) imaging, and histological analyses. Results: The PLA tubes were successfully designed and fabricated, exhibiting dimensions comparable to those of commercially available products. In vitro testing confirmed their biocompatibility. In vivo observations revealed that the PLA segments remained stable, with no significant inflammation detected. ABR measurements revealed no adverse impacts on hearing function. Micro-CT imaging confirmed tube integrity and indicated initial signs of degradation over a 9-month period, as evidenced by radiographic morphology. Histological analyses indicated a favorable tissue response with minimal foreign body reaction. Conclusions: The developed PLA middle-ear ventilation tube represents a highly promising alternative to conventional non-absorbable tubes. It demonstrates excellent biocompatibility, preserves auditory function, and exhibits a controlled degradation profile. This preclinical study provides strong support for further investigation and subsequent clinical trials to validate its safety and efficacy in human patients.