A Structural View at Vaccine Development against M. tuberculosis.

Tuberculosis (TB) is still the leading global cause of death from an infectious bacterial agent. Limiting tuberculosis epidemic spread is therefore an urgent global public health priority. As stated by the WHO, to stop the spread of the disease we need a new vaccine, with better coverage than the current Mycobacterium bovis BCG vaccine. This vaccine was first used in 1921 and, since then, there are still no new licensed tuberculosis vaccines. However, there is extremely active research in the field, with a steep acceleration in the past decades, due to the advance of technologies and more rational vaccine design strategies. This review aims to gather latest updates in vaccine development in the various clinical phases and to underline the contribution of Structural Vaccinology (SV) to the development of safer and effective antigens. In particular, SV and the development of vaccine adjuvants is making the use of subunit vaccines, which are the safest albeit the less antigenic ones, an achievable goal. Indeed, subunit vaccines overcome safety concerns but need to be rationally re-engineered to enhance their immunostimulating effects. The larger availability of antigen structural information as well as a better understanding of the complex host immune response to TB infection is a strong premise for a further acceleration of TB vaccine development.

Six-month longitudinal immune kinetics after mRNA-1273 vaccination: Correlation of peak antibody response with long-term, cross-reactive immunity.

Background: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the persistence of the pandemic, even with mass coronavirus disease 2019 (COVID-19) vaccination, have raised questions about the durability of immunity and extent of cross-reactive immunity after vaccination. This study aimed to characterize the humoral and cellular immune response to the mRNA-1273 vaccine using a prospective longitudinal cohort. Methods: We recruited 177 young SARS-CoV-2 infection-naive adults. Two doses of mRNA-1273 vaccine were administered at 28-day intervals, and blood samples were collected at five time points: pre-vaccination (T0), 4 weeks after the first (T1) and second dose (T2), and 3 months (T3) and 6 months (T4) after the first dose. Anti-SARS-CoV-2 spike protein (anti-S) IgG antibody, neutralizing antibody, and T-cell immune responses were evaluated. Results: The two-dose mRNA-1273 vaccination induced robust anti-SARS-CoV-2 antibody responses, which remained higher than the titers at T1 until T4. A higher peak anti-S antibody titer at T2 was associated with better cross-reactive immunity against Delta and Omicron variants and long-lasting (anti-S IgG and neutralizing antibody) humoral immunity up to T4. The overall T-cell immune response was not correlated with peak antibody titers (T-lymphocyte subpopulation analysis was not performed). Conclusion: This study showed that an early strong antibody response is predictive of longer humoral immunity and better cross-reactive neutralizing immunity against Delta and Omicron variants.

Six-month longitudinal immune kinetics after mRNA-1273 vaccination: Correlation of peak antibody response with long-term, cross-reactive immunity

Background The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the persistence of the pandemic, even with mass coronavirus disease 2019 (COVID-19) vaccination, have raised questions about the durability of immunity and extent of cross-reactive immunity after vaccination. This study aimed to characterize the humoral and cellular immune response to the mRNA-1273 vaccine using a prospective longitudinal cohort. Methods We recruited 177 young SARS-CoV-2 infection-naive adults. Two doses of mRNA-1273 vaccine were administered at 28-day intervals, and blood samples were collected at five time points: pre-vaccination (T0), 4 weeks after the first (T1) and second dose (T2), and 3 months (T3) and 6 months (T4) after the first dose. Anti-SARS-CoV-2 spike protein (anti-S) IgG antibody, neutralizing antibody, and T-cell immune responses were evaluated. Results The two-dose mRNA-1273 vaccination induced robust anti-SARS-CoV-2 antibody responses, which remained higher than the titers at T1 until T4. A higher peak anti-S antibody titer at T2 was associated with better cross-reactive immunity against Delta and Omicron variants and long-lasting (anti-S IgG and neutralizing antibody) humoral immunity up to T4. The overall T-cell immune response was not correlated with peak antibody titers (T-lymphocyte subpopulation analysis was not performed). Conclusion This study showed that an early strong antibody response is predictive of longer humoral immunity and better cross-reactive neutralizing immunity against Delta and Omicron variants.

Development of the Stress and Anxiety to Viral Epidemics-9 (SAVE-9) Scale for Assessing Work-related Stress and Anxiety in Healthcare Workers in Response to Viral Epidemics.

BACKGROUND: The coronavirus disease 2019, or COVID-19, has had a major psychological impact on healthcare workers. However, very few scales are available to specifically assess work-related stress and anxiety in healthcare workers responding to a viral epidemic. This study developed a new assessment tool, the Stress and Anxiety to Viral Epidemics-9 (SAVE-9) and aimed to validate it among healthcare workers directly affected by COVID-19 in Korea. METHODS: A total of 1,019 healthcare workers responded through anonymous questionnaires during April 20-30, 2020. Exploratory factor analysis (EFA) was conducted to explore the construct validity, and the reliability was assessed using internal consistency measures of Cronbach's alpha coefficients. Receiver operating characteristic analysis was conducted to define the most appropriate cut-off point of SAVE-9 using the Generalized Anxiety Disorder-7 scale (GAD-7; ≥ 5). Second, Spearman's rank correlation coefficient was used to establish convergent validity for the SAVE-9 questionnaire with GAD-7 and the Patient Health Questionnaire-9. RESULTS: The nine-item scale had satisfactory internal consistency (Cronbach's α = 0.795). It adopted a two-factor structure: 1) anxiety regarding viral epidemics and 2) work-related stress associated with viral epidemics. A cut-off score of 22 for the SAVE-9 ascertained levels of stress and anxiety in response to a viral epidemic in healthcare workers that warranted clinical attention. Correlations between the SAVE-9 and the other scales were statistically significant (P < 0.05). CONCLUSION: The results suggest that the SAVE-9 is a useful, reliable, and valid tool to evaluate stress and anxiety responses in healthcare workers during viral epidemics.

Clinical Trial: Magnetoplasmonic ELISA for Urine-based Active Tuberculosis Detection and Anti-Tuberculosis Therapy Monitoring.

The coronavirus disease 2019 (COVID-19) pandemic has proved the importance of fast and widespread diagnostic testing to prevent serious epidemics timely. The first-line weapon against rapidly transmitted disease is a quick and massive screening test to isolate patients immediately, preventing dissemination. Here, we described magnetoplasmonic nanozymes (MagPlas NZs), i.e., hierarchically coassembled Fe3O4-Au superparticles, that are capable of integrating magnetic enrichment and catalytic amplification, thereby the assay can be streamlined amenable to high-throughput operation and achieve ultrahigh sensitivity. Combining this advantage with conventional enzyme-linked immunosorbent assay (ELISA), we propose a MagPlas ELISA for urine-based tuberculosis (TB) diagnosis and anti-TB therapy monitoring, which enables fast (<3 h), and highly sensitive (up to pM with naked-eyes, < 10 fM with plate reader) urinary TB antigen detection. A clinical study with a total of 297 urine samples showed robust sensitivity for pulmonary tuberculosis (85.0%) and extra-pulmonary tuberculosis (52.8%) patients with high specificity (96.7% and 96.9%). Furthermore, this methodology offers a great promise of noninvasive therapeutic response monitoring, which is impracticable in the gold-standard culture method. The MagPlas ELISA showed high sensitivity comparable to the PCR assay while retaining a simple and cheap ELISA concept, thus it could be a promising point-of-care test for TB epidemic control and possibly applied to other acute infections.

High Work-Related Stress and Anxiety as a Response to COVID-19 Among Health Care Workers in South Korea: Cross-sectional Online Survey Study.

BACKGROUND: The COVID-19 outbreak had a severe impact on health care workers' psychological health. It is important to establish a process for psychological assessment and intervention for health care workers during epidemics. OBJECTIVE: We investigated risk factors associated with psychological impacts for each health care worker group, to help optimize psychological interventions for health care workers in countries affected by the COVID-19 pandemic. METHODS: Respondents (n=1787) from 2 hospitals in Korea completed a web-based survey during the period from April 14 to 30, 2020. The web-based survey collected demographic information, psychiatric history, and responses to the 9-item Stress and Anxiety to Viral Epidemics (SAVE-9), 9-item Patient Health Questionnaire (PHQ-9), and 7-item Generalized Anxiety Disorder-7 (GAD-7) scales. We performed logistic regression to assess contributing factors as predictor variables, using health care workers' depression as outcome variables. RESULTS: Among 1783 health care workers, nursing professionals had significantly higher levels of depression (PHQ-9 score: meannurse 5.5, SD 4.6; meanother 3.8, SD 4.2; P<.001), general anxiety (GAD-7 score: meannurse 4.0, SD 4.1; meanother 2.7, SD 3.6; P<.001), and virus-related anxiety symptoms (SAVE-9 score: meannurse 21.6, SD 5.9; meanother 18.6, SD 6.3; P<.001). Among nursing professionals, single workers reported more severe depressive symptoms than married workers (PHQ-9 score ≥10; meannurse 20.3%; meanother 14.1%; P=.02), and junior (<40 years) workers reported more anxiety about the viral epidemic (SAVE-9 anxiety score; meannurse 15.6, SD 4.1; meanother 14.7, SD 4.4; P=.002). Logistic regression revealed that hospital (adjusted odds ratio [OR] 1.45, 95% CI 1.06-1.99), nursing professionals (adjusted OR 1.37, 95% CI 1.02-1.98), single workers (adjusted OR 1.51, 95% CI 1.05-2.16), higher stress and anxiety to the viral infection (high SAVE-9 score, adjusted OR 1.20, 95% CI 1.17-1.24), and past psychiatric history (adjusted OR 3.26, 95% CI 2.15-4.96) were positively associated with depression. CONCLUSIONS: Psychological support and interventions should be considered for health care workers, especially nursing professionals, those who are single, and those with high SAVE-9 scores.

Functional Impairments in the Mental Health, Depression and Anxiety Related to the Viral Epidemic, and Disruption in Healthcare Service Utilization among Cancer Patients in the COVID-19 Pandemic Era.

PURPOSE: Literature is scarce regarding cancer care utilization during the massive outbreak of coronavirus disease 2019 (COVID-19) in the Republic of Korea. We investigated functional impairments in mental health and their relationships with depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization among cancer patients in the COVID-19 pandemic era. MATERIALS AND METHODS: We used an online survey with questions related to the disturbances faced by patients with cancer in utilizing healthcare services in the pandemic era. Current mental health status was assessed using the Work and Social Adjustment Scale (WSAS), Stress and Anxiety to Viral Epidemics-6 (SAVE-6) scale, Patient Health Questionnaire-9 (PHQ-9), Insomnia Severity Index (ISI), Brief Resilience Scale (BRS), Cancer-Related Dysfunctional Beliefs about Sleep Scale (C-DBS), and Fear of COVID-19 over Cancer (FCC). RESULTS: Among the 221 responders, 95 (43.0%) reported disruptions in healthcare service utilization during the COVID-19 pandemic. Logistic regression analysis revealed that functional impairment in the mental health of these patients was expected due to disruptions in healthcare service utilization, high levels of depression, anxiety regarding the viral epidemic, fear of COVID over cancer, and low resilience. Mediation analysis showed that patient resilience and cancer-related dysfunctional beliefs about sleep partially mediated the effects of viral anxiety on functional impairment. CONCLUSION: In this pandemic era, patients with cancer experience depression, anxiety regarding the viral epidemic, and disruptions in healthcare service utilization, which may influence their functional impairments in mental health.

Application of the Stress and Anxiety to Viral Epidemics-6 (SAVE-6) and Coronavirus Anxiety Scale (CAS) to Measure Anxiety in Cancer Patient in Response to COVID-19.

This study investigated the usefulness of the six-item Stress and Anxiety to Viral Epidemics (SAVE-6) scale and the Coronavirus Anxiety Scale (CAS) as tools to assess anxiety related to coronavirus disease (COVID-19) in cancer patients. A total of 221 patients with cancer responded to an anonymous online questionnaire between 15 July and 15 August 2020. The functional impairment of the patients was assessed using the Work and Social Adjustment Scale (WSAS), and the SAVE-6 and CAS were also applied. Among these 221 cancer patients, 110 (49.8%) had SAVE-6 scores ≥ 15 and 21 (9.5%) had CAS scores ≥ 5. Within the study population, 104 (47.1%) and 29 (13.1%) patients had WSAS scores ≥ 11 (moderate to severe functional impairment) and ≥ 21 (severe functional impairment), respectively. The correlations between the SAVE-6 and WSAS (p < 0.001) and CAS (p < 0.001) scores were statistically significant. The cut-off for the SAVE-6 was 15 points, while that for the WSAS was 11. Our results suggested that the SAVE-6 and CAS could be used to evaluate moderate and severe degrees of functional impairment related to mental health, respectively, in cancer patients during viral epidemics.