Search

HeberNasvac is a recently developed therapeutic vaccine for chronic hepatitis B (CHB) administered by intranasal (IN) and subcutaneous (SC) routes in a 14 days/10 doses schedule. To compare different schedules and routes of immunizations, a group of patients received four different vaccination regimens in a placebo-controlled factorial study. Subsequently, patients were followed for a minimum time of 48 weeks. Samples collected at the end of the follow-up were compared with initial samples. Groups I and II received the product by IN/SC routes, every 14 and 7 days, respectively. Groups III and IV were treated by SC route alone following a 14 and 7 days schedule. A group of 21 CHB patients received the vaccine in four different schedules and eight patients received placebo for a total of 29 patients enrolled. The 61.9% of vaccinees reduced their VL ≥2Log compared with baseline levels and 25% in placebo group. The 47.6% of vaccines reduced HBV levels to undetectable, 25% in placebo. HBeAg loss and seroconversion to anti-HBeAg was only achieved in vaccinees, 4 out of 9 (44.4%), and 40% (8 out of 20) developed anti-HBs response, none in placebo group. Reduction of HBsAg level in ≥1Log was achieved in the 35.0% of vaccinees and in none of the placebo-treated patients. Considering the individual and factorial analysis, significant HBV DNA reduction was detected in groups I and II, immunized by IN/SC routes. A significantly higher proportion of patients reducing VL to ≥2Log was also detected grouping the patients treated by IN/SC routes (G I + II) and grouping those inoculated every 14 days (G I + III), with 72.7% and 63.6%, respectively, compared with the placebo group (25.0%). The patients immunized every 14 days (G I + G III) also reduced the HBsAg levels compared with baseline. In conclusion, after more than 48 weeks of treatment-free follow-up, HeberNasvac-treated patients demonstrated superior responses compared with the placebo group in terms of antiviral and serological responses. The factorial analysis evidenced that the schedule combining the IN route of immunization and the frequency of 14 days resulted in the stronger antiviral and serological responses. Present results support the study of IN-only immunization schedules in future and was consistent with previous results. Long-lasting follow-ups were done to explore histological variables and the progression of serological variables in order to detect late responders. [ABSTRACT FROM AUTHOR]

The antigenicity of two recombinant NS3 proteins cloned in E. coli was compared by ELISA. The truncated rNS3 recombinant protein encompasses the amino acids from 1234 to 1432 of the Hepatitis C Virus (HCV) polyprotein, and the CIB-c33c protein encloses the entire HCV c33c sequence (aa 1192-1457). Seroconversion sera to NS3 from the Boston Biomedical panel PHV908 were used for evaluation. Our results show that the CIB-c33c protein has a better antigenicity than the rNS3 protein. Antigen CIB-c33c was recognized by the sera at the HCV seroconversion phase exclusively with antibodies against the NS3 region. Comparisons between both proteins suggest that the 25 aa fragment sequence presented at the c33c carboxyl-terminal is important for antibody recognition. The synthetic peptide encompassing this 25 amino acid fragment was not recognized by sera in seroconversion for HCV, suggesting that this fragment requires the presence of the remaining c33c region to expose its antigenicity. The new variant of the c33c protein obtained (CIB-c33c), expressed at high levels in E. coli and highly purified (>90% of purity) by onestep metal affinity chromatography, showed improved antigenic properties. Moreover, it increased the performance of anti-HCV diagnosis, and was able to detect sera in the seroconversion phase, thereby reducing the diagnostic seronegative window. [ABSTRACT FROM AUTHOR]

Introduction: More than 180 million people have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and more than 4 million coronavirus disease-2019 (COVID-19) patients have died in 1.5 years of the pandemic. A novel therapeutic vaccine (NASVAC) has shown to be safe and to have immunomodulating and antiviral properties against chronic hepatitis B (CHB)., Materials and Methods: A phase I/II, open-label controlled and randomized clinical trial of NASVAC as a postexposure prophylaxis treatment was designed with the primary aim of assessing the local and systemic immunomodulatory effect of NASVAC in a cohort of suspected and SARS-CoV-2 risk-contact patients. A total of 46 patients, of both sexes, 60 years or older, presenting with symptoms of COVID-19 were enrolled in the study. Patients received NASVAC (100 μg per Ag per dose) via intranasal at days 1, 7, and 14 and sublingual, daily for 14 days., Results and Discussion: The present study detected an increased expression of toll-like receptors (TLR)-related genes in nasopharyngeal tonsils, a relevant property considering these are surrogate markers of SARS protection in the mice model of lethal infection. The HLA-class II increased their expression in peripheral blood mononuclear cell's (PBMC's) monocytes and lymphocytes, which is an attractive property taking into account the functional impairment of innate immune cells from the periphery of COVID-19-infected subjects. NASVAC was safe and well tolerated by the patients with acute respiratory infections and evidenced a preliminary reduction in the number of days with symptoms that needs to be confirmed in larger studies., Conclusions: Our data justify the use of NASVAC as preemptive therapy or pre-/postexposure prophylaxis of SARS-CoV-2 and acute respiratory infections in general. The use of NASVAC or their active principles has potential as immunomodulatory prophylactic therapies in other antiviral settings like dengue as well as in malignancies like hepatocellular carcinoma where these markers have shown relation to disease progression., How to Cite This Article: Fleites YA, Aguiar J, Cinza Z, et al. HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis. Euroasian J Hepato-Gastroenterol 2021;11(2):59-70., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

The Dengue IgM Capture ELISA (MAC-ELISA) is the immunoenzymatic system recommended by the Pan American Health Organization and the World Health Organization for the serological diagnosis of dengue virus infection due to its high sensitivity, ease of performance, and use of a single acute-phase serum sample. However, tests with this enzyme-linked immunosorbent assay (ELISA) system are time-consuming and require equipment for washing, incubation, and reading of the results. AuBioDOT is a multistep visual diagnostic immunoassay that uses technology based on the immunoglobulin M (IgM) capture ELISA principle. This system uses white polyethylene opaque plates as the solid phase, colloidal gold as the marker, and silver ion amplification. It does not require special equipment, it is totally manually operated, and it can be performed in less than 1 h. The sensitivity and specificity of AuBioDOT for the detection of anti-dengue virus IgM antibodies were studied with a panel of 336 serum samples (150 serum samples from patients with suspected or serologically confirmed dengue virus infection, 186 serum samples from healthy blood donors and patients without dengue virus infection). The results were compared with those obtained by the MAC-ELISA. A sensitivity of 97.7% and a specificity of 97.1% were obtained. The concordance of the two tests was 97.3%, with a kappa index of 0.94. The application of AuBioDOT for the detection of anti-dengue virus IgM antibodies is recommended as an alternative method for the diagnosis of dengue virus infection, both for clinical diagnosis and for seroepidemiological surveillance. The system is useful under field conditions and in laboratories and requires little equipment.