Immune Responses and Protection Profiles in Mice Induced by Subunit Vaccine Candidates Based on the Extracellular Domain Antigen of Respiratory Syncytial Virus G Protein Combined with Different Adjuvants.

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract disease of infants and older people. There is an urgent need for safe and effective vaccines against RSV infection. In this study, we analyzed the effects of the immune response and protection with the RSV recombinant G protein extracellular domain (Gecto) combined with various adjuvants as novel subunit vaccines in mice. All groups receiving RSV Gecto combined with adjuvants exhibited robust humoral and cellular immunity compared to those receiving an adjuvant alone or inactivated RSV vaccine. The greatest effect was observed in mice receiving Gecto combined with a CpG ODN + Alum salt adjuvant, resulting in the highest production of neutralizing antibodies against both RSV A and B subtypes, G-specific IgG and IFN-γ production in splenocytes, and interleukin-2 and interferon-γ expression in CD4+ T cells. Significant humoral and cellular immune responses were observed in mice immunized with Gecto combined with AddaS03™ or cyclosporin A adjuvants. The vaccine containing the AddaS03™ adjuvant showed significantly high expression of interleukin-4 in CD4+ T cells. Cross-protection against a challenge with either RSV A or B subtypes was observed in the Gecto plus adjuvant groups, resulting in a significant decrease in viral load and reduced pathological damage in the mouse lungs. These findings offer valuable insights into the development and application of recombinant RSV G-subunit vaccines with adjuvants.

Single-Dose Intranasal Immunisation with Novel Chimeric H1N1 Expressing the Receptor-Binding Domain of SARS-CoV-2 Induces Robust Mucosal Immunity, Tissue-Resident Memory T Cells, and Heterologous Protection in Mice.

Current COVID-19 vaccines can effectively reduce disease severity and hospitalisation; however, they are not considerably effective in preventing infection and transmission. In this context, mucosal vaccines are pertinent to prevent SARS-CoV-2 infection and spread. In this study, we generated a replication-competent recombinant chimeric influenza A virus (IAV) expressing the receptor-binding domain (RBD) of a SARS-CoV-2 prototype in the C-terminus of the neuraminidase (NA) of A/Puerto Rico/08/1934 H1N1 (PR8). The remaining seven segments from A/WSN/1933 H1N1 (WSN) were named PR8NARBD/WSN. We observed that the recombinant virus with the WSN backbone demonstrated improved expression of NA and RBD. A single intranasal dose of PR8NARBD/WSN(103PFU) in mice generated robust mucosal immunity, neutralising antibodies, cellular immunity, and tissue-resident memory T cells specific to SARS-CoV-2 and IAV. Importantly, immunisation with PR8NARBD/WSN viruses effectively protected mice against lethal challenges with H1N1, H3N2 IAV, and SARS-CoV-2 Beta variant and significantly reduced lung viral loads. Overall, our research demonstrates the promising potential of PR8NARBD/WSN as an attractive vaccine against emerging SARS-CoV-2 variants and influenza A virus infections.

Higher central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia.

AIM: To assess central set point of thyroid homeostasis in drug-naïve patients affected by first episode schizophrenia. METHODS: This cross-sectional study was conducted in Xinxiang city, Henan, China. Patients were drug-naïve patients affected by first episode schizophrenia, aged 14-50 years old and admitted to the "Second Affiliated Hospital of Xinxiang Medical University" from January 2018 to December 2018. Controls were healthy individuals who underwent annual health from Xinxiang city, a community population of the same age and time period. The parameters of "central set point of thyroid homeostasis" were measured by "thyroid-stimulating hormone (TSH) index" and "thyroid feedback quantile-based index". The parameters were compared between schizophrenia patients and controls. Linear regression models adjusted by age and sex were used to assess the association of schizophrenia with the parameters. RESULTS: A total of 235 patients and 121 controls were included in this study. Patients affected by schizophrenia had significantly higher prevalence of hyperthyroxinemia and levels of free T4, "TSH index", and "thyroid feedback quantile-based index" than controls. After adjusting age and sex, schizophrenia was independently associated with the higher level of "TSH index" (adjusted ß 0.33, 95 % confidence interval 0.17, 0.49) and "thyroid feedback quantile-based index" (adjusted ß 0.21, 95 % confidence interval 0.12, 0.30). The results with age and sex matched patients and controls were similar to those observed in the overall study population. CONCLUSION: Higher central set point may be the underlying mechanism of thyroid allostatic load in drug-naïve patients affected first episode schizophrenia.