Precise modification of the surface charge of antigen enhances vaccine immunogenicity.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

The negative impact of loneliness and perceived stress on mental health during two-month lockdown in Shanghai.

BACKGROUND: Shanghai undergone COVID-19 lockdown for 2 months in 2022, affecting >25 million population. We aim to find changes in mental health during Shanghai lockdown and if mental health was associated with Shanghai lockdown, loneliness, and perceived stress. METHODS: We conducted two cross-sectional online surveys in China, which were before and at the end of Shanghai lockdown (survey 1 in January 2022, N = 1123; survey 2 in June 2022, N = 2139). Participants reported mental health, loneliness, and perceived stress through the 12-item General Health Questionnaire (GHQ-12), the short-form UCLA Loneliness Scale (ULS-8), and the 10-item Perceived Stress Scale (PSS-10). We compared data between survey 1 and 2. We ran a multiple linear regression model to investigate the impact of Shanghai lockdown, loneliness and perceived stress on mental health. RESULTS: There's an increase in the proportion of lonely people during Shanghai lockdown (49.77 % to 65.26 %). During Shanghai lockdown, the proportion of lonely people (68.97 % VS. 61.35 %, p < 0.001) and risk for mental health conditions (50.50 % VS. 43.27 %, p < 0.001) were higher among residents in Shanghai than outside Shanghai. Shanghai lockdown (b = 0.556, p = 0.02), higher ULS-8 (b = 0.284, p < 0.001) and higher PSS-10 (b = 0.365, p < 0.001) were associated with higher GHQ-12. LIMITATIONS: Participants reported their mental health status during Shanghai lockdown retrospectively. CONCLUSION: Shanghai lockdown had psychological impacts not only on residents in Shanghai but also outside Shanghai. Addressing loneliness and perceived stress accommodated to the lockdown situation should be considered.

Lung-Targeted Transgene Expression of Nanocomplexed Ad5 Enhances Immune Response in the Presence of Preexisting Immunity.

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5-host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus-adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

Recombinant Human Thymosin Beta-4 Protects against Mouse Coronavirus Infection.

Coronaviruses (CoVs) are enveloped and harbor an unusually large (30-32 kb) positive-strand linear RNA genome. Highly pathogenic coronaviruses cause severe acute respiratory syndrome (SARS) (SARS-CoV and SARS-CoV-2) and Middle East respiratory syndrome (MERS) (MERS-CoV) in humans. The coronavirus mouse hepatitis virus (MHV) infects mice and serves as an ideal model of viral pathogenesis, mainly because experiments can be conducted using animal-biosafety level-2 (A-BSL2) containment. Human thymosin beta-4 (Tß4), a 43-residue peptide with an acetylated N-terminus, is widely expressed in human tissues. Tß4 regulates actin polymerization and functions as an anti-inflammatory molecule and an antioxidant as well as a promoter of wound healing and angiogenesis. These activities led us to test whether Tß4 serves to treat coronavirus infections of humans. To test this possibility, here, we established a BALB/c mouse model of coronavirus infection using mouse CoV MHV-A59 to evaluate the potential protective effect of recombinant human Tß4 (rhTß4). Such a system can be employed under A-BSL2 containment instead of A-BSL3 that is required to study coronaviruses infectious for humans. We found that rhTß4 significantly increased the survival rate of mice infected with MHV-A59 through inhibiting virus replication, balancing the host's immune response, alleviating pathological damage, and promoting repair of the liver. These results will serve as the basis for further application of rhTß4 to the treatment of human CoV diseases such as COVID-19.

Mental Symptoms and Stress of Hospitalized Schizophrenia Patients With 2019 Novel Coronavirus Disease: An Observation Study.

Background: The 2019 novel coronavirus disease (COVID-19) is an extremely rapidly spreading respiratory infection caused by SARS-CoV-2. Many schizophrenic patients were infected with COVID-19 in Wuhan City, Hubei Province. This study took hospitalized schizophrenia patients with COVID-19 as the research subjects and observed the changes in psychopathology and stress of patients with COVID-19 and the accompanying social isolation. Methods: To sort and isolate potential COVID-19-infected patients, an isolated ward was set up from January 30, 2020, to March 30, 2020. Schizophrenia patients with COVID-19 were referred to this ward, and long-term hospitalized cases were included in this study. The Positive and Negative Syndrome Scale and Perceived Stress Scale were used to evaluate the severity of mental symptoms and psychological stress in the early stage of the outbreak of COVID-19, after the diagnosis of COVID-19 and after recovery. At the time of diagnosis, we also extracted the patient's routine blood, biochemical and other indicators and asked the patient's perception of COVID-19. Results: 21 hospitalized schizophrenia patients with COVID-19 were recruited in this study. The changes in PANSS scores were not significant (p = 0.225 baseline vs. diagnosed, p = 0.399 cured vs. diagnosed). The CPSS scores increased significantly after diagnosis and transfer to the isolation ward (p < 0.001 baseline vs. diagnosed, p < 0.001 cured vs. diagnosed). The course of schizophrenia was a protective factor of stress levels to cases (t = -3.25, p = 0.006), and patients' perception of COVID-19 was a risk factor (t = 2.48, p = 0.038). The final multiple linear regression model was statistically significant (F = 8.16, p < 0.001). Conclusion: Hospitalized schizophrenia patients with COVID-19 had increased stress levels and negative symptoms but alleviated positive symptoms after medical isolated treatment. This reminds us that in the face of major epidemics, we must specifically alleviate the psychological burden at the peak of the epidemic and improve the prognosis of patients after the epidemic.

Maintaining treatment and prevention programs for opioid use disorders during the coronavirus disease 2019 pandemic.

PURPOSE OF REVIEW: The current article reviews the impact of the biggest health crisis for many decades, coronavirus disease 2019 (COVID-19), on opioid treatment programs and the strategies adopted for maintaining opioid treatment programs during the pandemic. RECENT FINDINGS: The difficulty of access to opioid treatment services and the mental health problems accompanying opioid use disorders are the two main challenges to maintaining accessible and effective opioid treatment. Many countries and institutions issued guidance and recommendations to address these challenges. General coping strategies, loosening of policies, telemedicine, and depot buprenorphine are four main strategies to cope with the challenges posed by the pandemic. SUMMARY: There were considerable obstacles to maintaining opioid intervention programs during the COVID-19 pandemic. Strategies addressing the obstacles are identified. Research in this area needs to be strengthened.