Safety and efficacy of dendritic cell vaccine for COVID-19 prevention after 1-Year follow-up: phase I and II clinical trial final result.

Introduction: Interim analysis of phase I and phase II clinical trials of personalized vaccines made from autologous monocyte-derived dendritic cells (DCs) incubated with S-protein of SARS-CoV-2 show that this vaccine is safe and well tolerated. Our previous report also indicates that this vaccine can induce specific T-cell and B cell responses against SARS-CoV-2. Herein, we report the final analysis after 1 year of follow-up regarding its safety and efficacy in subjects of phase I and phase II clinical trials. Methods: Adult subjects (>18 years old) were given autologous DCs derived from peripheral blood monocytes, which were incubated with the S-protein of SARS-CoV-2. The primary outcome is safety in phase I clinical trials. Meanwhile, optimal antigen dosage is determined in phase II clinical trials. Corona Virus Disease 2019 (COVID-19) and Non-COVID-19 adverse events (AEs) were observed for 1 year. Results: A total of 28 subjects in the phase I clinical trial were randomly assigned to nine groups based on antigen and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) dosage. In the phase II clinical trial, 145 subjects were randomly grouped into three groups based on antigen dosage. During the 1-year follow-up period, 35.71% of subjects in phase I and 16.54% in phase II had non-COVID AEs. No subjects in phase I experienced moderate-severe COVID-19. Meanwhile, 4.31% of subjects in phase II had moderate-severe COVID-19. There is no difference in both COVID and non-COVID-19 AEs between groups. Conclusions: After 1 year of follow-up, this vaccine is proven safe and effective for preventing COVID-19. A phase III clinical trial involving more subjects should be conducted to establish its efficacy and see other possible side effects.

Latent tuberculosis infection in family members in household contact with active tuberculosis patients in Semarang City, Central Java, Indonesia.

A quarter of the world's population is infected with Mycobacterium tuberculosis (M.tb), 10% of cases develop active tuberculosis (TB), and 90% have a latent TB infection. Family members of TB patients have the highest potential for latent TB infection. This study aims to identify latent TB infection and risk factors in family members within the household contacts of active TB patients. This study used a crosssectional study design with a contact tracing method. The selected subjects were 138 people from 241 total family members of 112 active TB patients. Subjects underwent a tuberculin skin test (TST), using 2 units of tuberculin (TU) purified protein derivative (PPD) 0.1 mL (PT. Bio Farma Persero, Bandung, Indonesia). Data risk factors were collected during home visits. Data were analyzed using the chi-square test and multiple logistic regression. A total of 63.8% (88/138) of family members of active TB patients' household contacts had latent TB infection. The type of occupation of laborers/ farmers/fishers is the most dominant risk factor associated with latent TB infection (AOR: 7.04; 95% CI: 1.70-29.02), followed by unqualified bedroom density (<8 m2/2 people) (AOR: 5.33; 95% CI: 2.44- 12.71) and contact duration ≥5 hours/day (AOR: 4.70; 95% CI:1.33-16.66). Latent TB infection in family members of active TB patients' household contacts was quite high. Occupation type, contact duration, and bedroom density were simultaneously confirmed as the main risk factors related to latent TB infection. Therefore, it is recommended to identify and prevent latent TB infection in family members in household contact with active TB patients.

A Case-Control Study of the MTHFR C665T Gene Polymorphism on Macrocytic Anemia Among HIV-Infected Patients Receiving Zidovudine.

Background: Macrocytic anemia is the most common anemia in HIV-infected patients receiving zidovudine, and is closely related to folate and vitamin B12 deficiencies. Homocysteine >10 µmol/L and increased MMA (methylmalonic acid) levels >24.8 ng/mL indicate high/low folate and vitamin B12 deficiencies. Furthermore, MTHFR (Methylene-tetrahydrofolate-reductase) plays an essential role in the transmethylation of homocysteine to methionine and is related to DNA synthesis. The MTHFR C665T gene polymorphism decreases the activity of MTHFR, which culminates in homocysteinemia. Therefore, this case-control aims to assess the role of the MTHFR C665T gene polymorphism on the risk of macrocytic anemia among HIV-infected individuals receiving zidovudine. Methods: This study was conducted using an unmatched case-control design and the participants were HIV-infected adults aged 20 to 59 years old, receiving zidovudine for four weeks and above. A sample of 232 patients was divided into case group with macrocytic anemia and the control having no anemia. Multivariate logistic regression analysis was then implemented to determine the risk factors. Results: The results showed that there was a significant difference in the number of female and male patients namely 51.3% and 48.7%, respectively, with p< 0.001. Moreover, the mean age of the cases and control group was 41.9 ± 9.4 and 36.2 ± 8.3. Regarding education, there were significant differences between subjects with low and high education 47.8% vs 52.2% with p<0.001. The majority of patients or 90.95% had taken AZT for more than 6 months. The logistic regression analysis test results showed that sex, age, education level, duration of AZT use, and homocysteine levels were predictors of macrocytic anemia with p<0.05, while MTHFR C665T gene polymorphism and MMA levels were not risk factors. Conclusion: MTHFR C665T gene polymorphism does not contribute to the incidence of macrocytic anemia among HIV-infected individuals receiving zidovudine.

Correlation of miR-150, hsa-let-7e, and miR- 146a and gene expression of IL-6, IL-8, IP-10, and MIP-1ß during dengue virus infection.

Growing evidence suggests that microRNAs (miRNAs) play a pivotal role in viral infection. The objective of this study was to assess the association between the expression of miR- 150, hsa-let-7e, and miR-146a on cytokine expression during dengue infection. Dengue virus (DENV) strain SJN-006, a serotype 2 DENV strain of the Cosmopolitan genotype, isolated in Bali, Indonesia, was used to infect peripheral blood mononuclear cells (PBMCs) isolated from healthy individuals. The relative gene expressions of miR-150, hsa-let-7e, and miR-146a as well as the gene expression of cytokines (IL-6, IL-8, IP-10, and MIP-1ß) were determined using quantitative real time - polymerase chain reaction (qRT-PCR) at 6, 12 and 24 hours post infection (hpi). Correlations between the microRNAs and cytokines were analyzed by means of causality tests. Our data suggests that miR-150 and hsa-let-7e were significantly higher in infected-PBMCs after 12 hpi compared to the uninfected-PBMCs (p<0.05). The causality tests demonstrated that miR-150 and has-let- 7e were negatively correlated with IL-8 expression, meanwhile miR-146a was the contrast. DENV infection was negatively and positively correlated with miR-150 and hsa-let-7e, respectively, after 24 hpi. In conclusion, our data demonstrates the vital role of miR-150, hsa-let-7e, and miR-146a in regulating IL-8 expression with possible different pathways.

Age and CD4 count are dominant factors in the prediction of anaemia in Javanese HIV patients.

BACKGROUND AND OBJECTIVES: Anaemia in Human Immunodeficiency Virus (HIV) infection is multifactorial and an increasingly important variable to consider in the management. This is the first study of anaemia in HIV infection in the Javanese population, which constitutes the largest ethnic group in Indonesia. The aim of this study was to determine the factors which are associated with anaemia in Javanese patients with HIV infection. METHODS AND STUDY DESIGN: This study applied a cross-sectional design involving HIV patients in Dr Kariadi Hospital and Balai Kesehatan Paru Masyarakat (BKPM), Semarang, Indonesia. The characteristic data of the subjects were age, gender, BMI, duration of therapy and antiretroviral (ARV) drugs. Haematology tests were conducted using flow cytometry. RESULTS: The prevalence of anaemia in HIV-infected patients was 21 (38.88%). Macrocytic anemia was found as a majority (12; 57.1 %) in anaemic patients. The risk factors which were found to be associated with increase of anaemia were white blood cells (WBC) <5.0 x 109/L and CD4 >200.0 cells/µL (p<0.05). A correlation between anaemia and age (r=0.49, p<0.01), duration of treatment (r=0.35, p<0.01), CD4 count (r=-0.42, p<0.01), total bilirubin (r=-0.28, p<0.05), and unconjugated bilirubin (r=-0.29, p<0.05) was identified. Age (p=0.023) and CD4 count (p=0.07) were the dominant factors in the multivariate analysis. CONCLUSION: Age and CD4 count are the dominant factors in determining of anaemia in Javanese patients with HIV infection.