The highly contagious SARS-CoV-2 Omicron subvariants severely attenuated the effectiveness of currently licensed SARS-CoV-2 vaccines based on ancestral strains administered via intramuscular injection. In this study, we generated a recombinant, replication-incompetent human adenovirus type 5, Ad5-S-Omicron, that expresses Omicron BA.1 spike. Intranasal, but not intramuscular vaccination, elicited spike-specific respiratory mucosal IgA and residential T cell immune responses, in addition to systemic neutralizing antibodies and T cell immune responses against most Omicron subvariants. We tested intranasal Ad5-S-Omicron as a heterologous booster in mice that previously received intramuscular injection of inactivated ancestral vaccine. In addition to inducing serum broadly neutralizing antibodies, there was a significant induction of respiratory mucosal IgA and neutralizing activities against Omicron subvariants BA.1, BA.2, BA.5, BA.2.75, BF.7 as well as pre-Omicron strains Wildtype, Beta, and Delta. Serum and mucosal neutralizing activities against recently emerged XBB, BQ.1, and BQ.1.1 could also be detected but were much lower. Nasal lavage fluids from intranasal vaccination contained multimeric IgA that can bind to at least 10 spike proteins, including Omicron subvariants and pre-Omicron strains, and possessed broadly neutralizing activities. Intranasal vaccination using Ad5-S-Omicron or instillation of intranasal vaccinee’s nasal lavage fluids in mouse nostrils protected mice against Omicron challenge. Taken together, intranasal Ad5-S-Omicron booster on the basis of ancestral vaccines can establish effective mucosal and systemic immunity against Omicron subvariants and multiple SARS-CoV-2 variants. This candidate vaccine warrants further development as a safe, effective, and user-friendly infection and transmission-blocking vaccine.

Human cytomegalovirus (HCMV), recognized as the largest known DNA virus in the Herpesviridae family, is widely disseminated throughout the human population and poses a substantial threat to public health. HCMV is highly infectious. A majority of HCMV-infected individuals usually exhibit asymptomatic latent infections, while the immunocompromised or immunosuppressed populations infected with HCMV have high mortality. HCMV has long stood as a hot topic of research in the international virology community, and elucidating its pathogenic mechanisms is broadly regarded as a prerequisite for the development of vaccines and effective therapeutic drugs. This review presents a comprehensive and detailed analysis of the advances in the biological characteristics, pathogenesis, virus-host interactions, and the preventive and therapeutic strategies targeting HCMV infection. It will provide valuable insights and references for uncovering the pathogenic mechanisms of HCMV, identifying new drug targets, and developing potential immunotherapies.

Introduction: Over the past decade, Corynebacterium striatum (C. striatum), an emerging multidrug-resistant (MDR) pathogen, has significantly challenged healthcare settings, especially those involving individuals with weakened immune systems. The rise of these superbugs necessitates innovative solutions.Methods: This study aimed to isolate and characterize bacteriophages targeting MDR-C. striatum. Utilizing 54 MDR-C. striatum isolates from a local hospital as target strains, samples were collected from restroom puddles for phage screening. Dot Plaque and Double-layer plate Assays were employed for screening.Results: A novel temperate bacteriophage, named CSP1, was identified through a series of procedures, including purification, genome extraction, sequencing, and one-step growth curves. CSP1 possesses a 39,752 base pair circular double-stranded DNA genome with HK97-like structural proteins and potential for site-specific recombination. It represents a new species within the unclassified Caudoviricetes class, as supported by transmission electron microscopy, genomic evolutionary analysis, and collinearity studies. Notably, CSP1 infected and lysed 21 clinical MDR-C. striatum isolates, demonstrating a wide host range. The phage remained stable in conditions ranging from -40 to 55°C, pH 4 to 12, and in 0.9% NaCl buffer, showing no cytotoxicity.Discussion: The identification of CSP1 as the first phage targeting clinical C. striatum strains opens new possibilities in bacteriophage therapy research, and the development of diagnostic and therapeutic tools against pathogenic bacteria.

The outbreaks of respiratory pathogens like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus (IV) have heightened the demand for highly effective vaccines that provide strong and durable immunity in human populations. However, immune responses to vaccination vary significantly among individuals and populations. Recent studies have demonstrated that the gut microbiota play an essential role in regulating respiratory pathogens vaccination-induced immune responses through the systemic effects of gut-lung axis on distant organs, the lungs. In this review, we first synthesize the changes in gut microbiota composition and immune responses that occur during respiratory pathogen infections and vaccination. Then, we discuss the underlying immunological mechanisms of bidirectional immunomodulatory effects between gut microbiota and vaccines. Finally, we explore the strategies for designing next-generation vaccines against respiratory pathogens in term of gut microbiota-mediated immunological pathway.

Background: High-risk human papillomavirus (hrHPV) infection is a necessary cause of almost all cervical cancers. Relative to hrHPV 16/18 infection, non-16/18 hrHPV infection is of less concern. However, the increasing prevalence of non-16/18 hrHPV infections has become an important public health issue. The early identification and treatment of cervical cytological abnormalities in women infected with non-16/18 hrHPV reduces the incidence of cervical cancer. To date, no study has examined the risk factors for cytological abnormalities in this high-risk population. Objective: This population-based, cross-sectional study aimed to identify the risk factors for cervical cytological abnormalities in women infected with non-16/18 hrHPV. Methods: A total of 314,587 women from the general population were recruited for cervical cancer screening at 136 primary care hospitals in Xiangyang, China. Of these, 311,604 women underwent HPV genotyping, and 17,523 non-16/18 hrHPV–positive women were referred for cytological screening according to the screening program. A logistic regression model was used to assess the risk factors for cytological abnormalities among these non-16/18 hrHPV–positive women. A separate analysis was performed to determine the factors influencing high-grade cytological abnormalities. Results: The non-16/18 hrHPV infection rate was 5.88% (18,323/311,604), which was 3-fold higher than that of hrHPV 16/18 (6068/311,604, 1.95%). Among the non-16/18 hrHPV–positive women who underwent ThinPrep cytologic test, the overall prevalence rates of cervical cytological abnormalities and high-grade cytological abnormalities were 13.46% (2359/17,523) and 1.18% (206/17,523), respectively. Multivariate logistic regression analysis revealed that women with middle or high school educational attainment were at a higher risk of having cytological abnormalities than those who received primary education (odds ratio [OR] 1.31, 95% CI 1.17-1.45; P<.001, and OR 1.32, 95% CI 1.14-1.53; P<.001, respectively). Living in rural areas (OR 2.58, 95% CI 2.29-2.90; P<.001), gravidity ≥3 (OR 2.77, 95% CI 1.19-6.45; P=.02), cervix abnormalities detected in pelvic examination (OR 1.22, 95% CI 1.11-1.34; P<.001), and having a cervical cancer screening 3 years ago (OR 0.79, 95% CI 0.62-1.00; P=.048) were associated with cytological abnormalities. The risk factors for high-grade cytological abnormalities included middle school education (OR 1.45, 95% CI 1.07-1.98; P=.02), living in rural regions (OR 1.52, 95% CI 1.10-2.10; P=.01), and cervix abnormality (OR 1.72, 95% CI 1.30-2.26; P<.001). Conclusions: The dominant epidemic of non-16/18 hrHPV infection is revealed in Chinese women. Multiple risk factors for cervical cytological abnormalities have been identified in women infected with non-16/18 hrHPV. These findings can provide important information for clinically actionable decisions for the screening, early diagnosis, intervention, and prevention of cervical cancer in non-16/18 hrHPV–positive women.