A decavalent composite mRNA vaccine against both influenza and COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 has had a persistent and significant impact on global public health for 4 years. Recently, there has been a resurgence of seasonal influenza transmission worldwide. The co-circulation of SARS-CoV-2 and seasonal influenza viruses results in a dual burden on communities. Additionally, the pandemic potential of zoonotic influenza viruses, such as avian Influenza A/H5N1 and A/H7N9, remains a concern. Therefore, a combined vaccine against all these respiratory diseases is in urgent need. mRNA vaccines, with their superior efficacy, speed in development, flexibility, and cost-effectiveness, offer a promising solution for such infectious diseases and potential future pandemics. In this study, we present FLUCOV-10, a novel 10-valent mRNA vaccine created from our proven platform. This vaccine encodes hemagglutinin (HA) proteins from four seasonal influenza viruses and two avian influenza viruses with pandemic potential, as well as spike proteins from four SARS-CoV-2 variants. A two-dose immunization with the FLUCOV-10 elicited robust immune responses in mice, producing IgG antibodies, neutralizing antibodies, and antigen-specific cellular immune responses against all the vaccine-matched viruses of influenza and SARS-CoV-2. Remarkably, the FLUCOV-10 immunization provided complete protection in mouse models against both homologous and heterologous strains of influenza and SARS-CoV-2. These results highlight the potential of FLUCOV-10 as an effective vaccine candidate for the prevention of influenza and COVID-19.IMPORTANCEAmidst the ongoing and emerging respiratory viral threats, particularly the concurrent and sequential spread of SARS-CoV-2 and influenza, our research introduces FLUCOV-10. This novel mRNA-based combination vaccine, designed to counteract both influenza and COVID-19, by incorporating genes for surface glycoproteins from various influenza viruses and SARS-CoV-2 variants. This combination vaccine was highly effective in preclinical trials, generating strong immune responses and ensuring protection against both matching and heterologous strains of influenza viruses and SARS-CoV-2. FLUCOV-10 represents a significant step forward in our ability to address respiratory viral threats, showcasing potential as a singular, adaptable vaccine solution for global health challenges.

Baloxavir marboxil use for critical human infection of avian influenza A H5N6 virus.

BACKGROUND: Recent outbreaks of avian influenza and ongoing virus reassortment have drawn focus on spill-over infections. The increase in human infections with highly pathogenic avian influenza H5N6 virus and its high fatality rate posed a potential threat, necessitating the search for a more effective treatment. METHODS: Longitudinal clinical data and specimens were collected from five H5N6 patients after admission. All patients received antiviral treatment of either sequential monotherapy of oseltamivir and baloxavir or the two drugs in combination. Severity of illness; viral load in sputum, urine, and blood; and cytokine levels in serum and sputum were serially analyzed. FINDINGS: All patients developed acute respiratory distress syndrome (ARDS) and viral sepsis within 1 week after disease onset. When delayed oseltamivir showed poor effects, baloxavir was administered and rapidly decreased viral load. In addition, levels of IL-18, M-CSF, IL-6, and HGF in sputum and Mig and IL-18 in serum that reflected ARDS and sepsis deterioration, respectively, were also reduced with baloxavir usage. However, three patients eventually died from exacerbation of underlying disease and secondary bacterial infection. Nonsurvivors had more severe extrapulmonary organ dysfunction and insufficient H5N6 virus-specific antibody response. CONCLUSIONS: For critical human cases of H5N6 infection, baloxavir demonstrated effects on viral load and pulmonary/extrapulmonary cytokines, even though treatment was delayed. Baloxavir could be regarded as a first-line treatment to limit continued viral propagation, with potential future application in avian influenza human infections and poultry workers exhibiting influenza-like illness. FUNDING: This work was funded by the National Natural Science Foundation of China (81761128014).

Containment of SARS-CoV-2 Delta strain in Guangzhou, China by quarantine and social distancing: a modelling study.

China detected the first case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with Delta variant in May 2021. We assessed control strategies against this variant of concern. We constructed a robust transmission model to assess the effectiveness of interventions against the Delta variant in Guangzhou with initial quarantine/isolation, followed by social distancing. We also assessed the effectiveness of alternative strategies and that against potentially more infectious variants. The effective reproduction number (Rt) fell below 1 when the average daily number of close contacts was reduced to ≤ 7 and quarantine/isolation was implemented on average at the same day of symptom onset in Guangzhou. Simulations showed that the outbreak could still be contained when quarantine is implemented on average 1 day after symptom onset while the average daily number of close contacts was reduced to ≤ 9 per person one week after the outbreak's beginning. Early quarantine and reduction of close contacts were found to be important for containment of the outbreaks. Early implementation of quarantine/isolation along with social distancing measures could effectively suppress spread of the Delta and more infectious variants.

Insights into the Unique Lung Microbiota Profile of Pulmonary Tuberculosis Patients Using Metagenomic Next-Generation Sequencing.

The microbiota plays an important role in human health and disease development. The lung microbiota profile in pulmonary tuberculosis (TB) patients and the effects of anti-TB treatment on the profile need to be determined thoroughly and comprehensively. This study primarily aimed to determine the lung microbiota profile associated with pulmonary TB and characterize the longitudinal changes during anti-TB treatment. A total of 53 participants, comprising 8 healthy individuals, 12 untreated pulmonary TB patients, 15 treated pulmonary TB patients, 11 cured pulmonary TB patients, and 7 lung cancer patients, were recruited in the present study. Bronchioalveolar lavage fluid (BALF) samples were collected from the above participants, and throat swabs were taken from healthy individuals. Microbiomes in the samples were examined using metagenomic next-generation sequencing (mNGS). Differences in microbiota profiles were determined through a comparison of the indicated groups. Our findings indicated that the BALF samples displayed decreased richness and diversity of the microbiota compared to those of the throat swab samples, and these two kinds of samples exhibited obvious separation on principal-coordinate analysis (PCoA) plots. Untreated pulmonary TB patients displayed a unique lung microbiota signature distinct from that of healthy individuals and lung cancer patients. Our data first demonstrated that anti-TB treatment with first-line drugs increases alpha diversity and significantly affects the beta diversity of the lung microbiota, while it also induces antibiotic resistance genes (ARGs). IMPORTANCE Characterization of the lung microbiota could lead to a better understanding of the pathogenesis of pulmonary TB. Here, we applied the metagenomic shotgun sequencing instead of 16S rRNA sequencing method to characterize the lung microbiota using the BALF samples instead of sputum. We found that alterations in the lung microbiota are associated with TB infection and that anti-TB treatment significantly affects the alpha and beta diversity of the lung microbiota in pulmonary TB patients. These findings could help us better understand TB pathogenesis.