HeberNasvac: Development and Application in the Context of Chronic Hepatitis B.

Unlabelled: The immune system plays a central role in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, the development of a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyzes the key variables related to the safety, efficacy, and effectiveness of CHB treatments.

Impact of the Route and Schedule of Immunization on the Serological and Virological Response of Chronic Hepatitis B Patients Treated with HeberNasvac.

Unlabelled: 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.

The Safety and Efficacy of a Therapeutic Vaccine for Chronic Hepatitis B: A Follow-Up Study of Phase III Clinical Trial.

The objective of the present study was to assess the safety and efficacy of a therapeutic vaccine containing both HBsAg and HBcAg (NASVAC) in patients with chronic hepatitis B (CHB) three years after the end of treatment (EOT) as a follow-up of a phase III clinical trial. NASVAC was administered ten times by the nasal route and five times by subcutaneous injection. A total of 59 patients with CHB were enrolled.

Sustained Antiviral and Liver Protection by a Nasal Therapeutic Vaccine (NASVAC, Containing Both HBsAg and HBcAg) in Patients with Chronic Hepatitis B: 2-Year Follow-Up of Phase III Clinical Trial.

A phase III clinical trial in treatment-naïve patients with chronic hepatitis B (CHB) revealed the safety and considerable therapeutic efficacy of a vaccine containing both hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) (NASVAC) at the end of treatment (EOT) and 24 weeks after EOT. Two years after EOT, we checked HBV DNA, alanine aminotransferase (ALT), and hepatitis B e antigen (HBeAg). The data reveal that 33 of 66 NASVAC-recipient CHB patients became negative for HBV DNA in the blood two years after EOT.

HeberNasvac, a Therapeutic Vaccine for Chronic Hepatitis B, Stimulates Local and Systemic Markers of Innate Immunity: Potential Use in SARS-CoV-2 Postexposure Prophylaxis.

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).

Role of Pegylated Interferon in Patients with Chronic Liver Diseases in the Context of SARS-CoV-2 Infection.

Unlabelled: The coronavirus 2019 (COVID-19) pandemic has resulted in 168 million cases and about 3.5 million deaths (as of May 26, 2021) during the last 18 months. These 18 months of the COVID-19 pandemic have been characterized by phases or waves of new cases, the emergence of new variants of the deadly virus, and several new complications.

Prescribing Patterns and Use of Risk-Reduction Tools After Implementing an Opioid-Prescribing Protocol.

Background: The literature on results from primary care-based opioid-prescribing protocols is small and results have been mixed. To advance this field, we evaluated whether opioid prescribing changed after a comprehensive protocol was implemented and whether change was associated with the number and type of risk reduction tools adopted.

Methods: Electronic medical record data were obtained for 2607 patients.

Five-year Follow-up of Chronic Hepatitis B Patients Immunized by Nasal Route with the Therapeutic Vaccine HeberNasvac.

A novel therapeutic vaccine for chronic hepatitis B (CHB) treatment comprising the recombinant hepatitis B surface (HBsAg) and nucleocapsid (HBcAg) antigens has been developed. Preclinical and clinical trials (CT) evidenced safety and immunogenicity in animal models as well as in phases I, II, and III clinical trials. A phase I CT has conducted in Cuba in 6 CHB patients refractory or incomplete responders to α-IFN.

Treatment of chronic hepatitis B naïve patients with a therapeutic vaccine containing HBs and HBc antigens (a randomized, open and treatment controlled phase III clinical trial).

Context: Current drugs for chronic hepatitis B therapy have a poor efficacy in terms of post-treatment sustained viral suppression and generate important side effects during and after therapy. Therapeutic vaccination with HBV antigens is an attractive alternative to test.

Objective: Evaluating the efficacy of a therapeutic vaccine candidate (designated NASVAC) containing both hepatitis B surface antigen (HBsAg) and core antigen (HBcAg) versus pegylated interferon (Peg-IFN) in naïve chronic hepatitis B patients.

High Functional Stability of a Low-cost HBV DNA qPCR Primer Pair and Plasmid Standard.

Aim: We studied the functional stability of a primer pair and the standard curve based on a plasmid carrying full-length HBV genome, from a novel low-cost real-time quantitative polymerase chain reaction (qPCR) assay. The assay was developed at the Center for Genetic Engineering and Biotechnology (CIGB) in Havana, to quantify the serum hepatitis B virus (HBV) DNA from chronic HBV-infected (CHB) patients.

Materials And Methods: In-house generated oligonucleotides and plasmids were incubated at 37°C during 1 month and compared with the same materials incubated at -20, 4, and 25°C during the same time in qPCR experiments.

HBV genotypic variability in Cuba.

The genetic diversity of HBV in human population is often a reflection of its genetic admixture. The aim of this study was to explore the genotypic diversity of HBV in Cuba. The S genomic region of Cuban HBV isolates was sequenced and for selected isolates the complete genome or precore-core sequence was analyzed.

Boosting controlled autoimmunity: a new therapeutic target for CNS disorders.

In most tissues, the immune system plays an essential role in protection, repair and healing. Although immunologically privileged, the CNS remains subject to a highly regulated form of immunosurveillance that is of increasing interest. There is evolving evidence that repair mechanisms within the CNS may be enhanced by exploiting an innate process of protective immunity.

Development of a nasal vaccine for chronic hepatitis B infection that uses the ability of hepatitis B core antigen to stimulate a strong Th1 response against hepatitis B surface antigen.

There are estimated to be 350 million chronic carriers of hepatitis B infection worldwide. Patients with chronic hepatitis B are at risk of liver cirrhosis with associated mortality because of hepatocellular carcinoma and other complications. An important goal, therefore, is the development of an effective therapeutic vaccine against chronic hepatitis B virus (HBV).

Ten species in one: DNA barcoding reveals cryptic species in the neotropical skipper butterfly Astraptes fulgerator.

Astraptes fulgerator, first described in 1775, is a common and widely distributed neotropical skipper butterfly (Lepidoptera: Hesperiidae). We combine 25 years of natural history observations in northwestern Costa Rica with morphological study and DNA barcoding of museum specimens to show that A. fulgerator is a complex of at least 10 species in this region.

Evolution of the transposable element Pokey in the ribosomal DNA of species in the subgenus Daphnia (Crustacea: Cladocera).

Pokey is a member of the piggyBac (previously called the TTAA-specific) family of transposons and inserts into a conserved region of the large subunit ribosomal RNA gene. This location is a "hot spot" for insertional activity, as it is known to contain other arthropod transposable elements. However, Pokey is unique in that it is the first DNA transposon yet known to insert into this region.

Mitochondrial DNA variation in North American populations of Daphnia obtusa: continentalism or cryptic endemism?

The morphological stasis of many freshwater crustaceans has resulted in the prior delineation of cosmopolitan species and has been explained by their capacity for long-distance dispersal. This study examines the phylogeography of Daphnia obtusa, a cladoceran thought to be widespread in North America. However, sequence variation of the mitochondrial cytochrome c oxidase subunit I gene indicates that this taxon is composed of two morphologically cryptic species, designated D.

Pokey, a new DNA transposon in Daphnia (cladocera: crustacea).

We report the complete sequence of two representatives of the transposable element, Pokey, isolated from the ribosomal DNA of the cladoceran, Daphnia pulicaria. We describe the general features of this element, which confirms its classification as a DNA transposon. We show that Pokey is similar to piggyBac and, as such, is a member of the TTAA-specific family of elements.

A phase I clinical trial of a multi-epitope polypeptide TAB9 combined with Montanide ISA 720 adjuvant in non-HIV-1 infected human volunteers.

A phase I clinical trial was performed to examine the safety and immunogenicity of a multi-epitope polypeptide comprising the central 15 amino acids of the V3 loop from six HIV-1 isolates. This protein called TAB9 was emulsified in Montanide ISA720 (Seppic, Paris) and administered intramuscularly at doses of 0, 0.2 and 1 mg to 24 healthy, HIV-1 seronegative adult males.

[Impact of an anti-hepatitis B virus (HBV) immunization program in patients undergoing dialysis in Havana, Cuba].

The follow-up of HBV markers in selected high infection risk populations, in patients from the hemodialysis and peritoneal dialysis services was used to assess the effectiveness of a special vaccination program. Viral infection markers were studied in prevalence cross sections of the whole population of patients, and also by recording the reports of clinical cases of hepatitis B occurred during that period in those groups of patients. The prevention program consisted of the vaccination of all patients negative to the viral markers and the indication of vaccination for the new cases during the period of the kidney disease, just before the start of the treatment at the hemodialysis unit; besides all the persons susceptible to infection that had already been included in the program, regardless of the stage of the disease.

Aggregation of recombinant hepatitis B surface antigen induced in vitro by oxidative stress.

In order to examine whether oxygen radicals could be responsible for aggregation of recombinant hepatitis B surface antigen (HBsAg) during its assembly in yeast, purified HBsAg was oxidized with ammonium peroxodisulphate (AP) and analyzed by non-denaturing and denaturing size exclusion chromatography, immunoassay and immunoelectron microscopy. As a result, peroxodisulphate radicals induced a reproducible aggregation of HBsAg. At 44 mM AP, the aggregation process took a few hours and the resulting structures were large, branched and non-antigenic.

Physico-chemical characterization of recombinant hepatitis B surface antigen by a multidimensional approach.

Initially, our work was directed to respond to the question: why hepatitis B surface antigen (HBsAg) produces a very broad peak in preparative size-exclusion chromatography (SEC). For this purpose, we used a multidimensional approach based on SEC fractionation of purified HBsAg followed by the individual analysis of SEC fractions by a battery of assays, such as SEC, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, enzyme-linked immunosorbent assay and transmission electron microscopy. As a result, HBsAg particles were shown to be heterogeneous in terms of particle assembly.

Evidence for the denaturation of recombinant hepatitis B surface antigen on aluminium hydroxide gel.

Despite the complexity of the subject of protein-alum interactions, a valuable information can be obtained by analyzing the adsorbed and desorbed protein by common physico-chemical methods. In the present work, to approach the adsorption of hepatitis B surface antigen (HBsAg) on alum, the experimental data were supported by complementary analyses of the adsorbed protein by immunoelectron microscopy and the desorbed protein by denaturing size-exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions. First, the depletion of HBsAg was investigated.

Aggregation of recombinant hepatitis B surface antigen in Pichia pastoris.

The combination of immunoaffinity and size-exclusion chromatography (SEC) is a powerful tool to analyze multiprotein particle assembly. This approach was used to investigate the source of aggregation of recombinant hepatitis B surface antigen (HBsAg) detected in purified material. As HBsAg aggregation does not originate in the stresses, such as the concentration of HBsAg solutions, temperature and chaotropic agents, it is less probable that the HBsAg aggregate is produced during the process.

Adsorption-desorption of recombinant hepatitis B surface antigen (r-HBsAg) from P. pastoris on a diatomaceous earth matrix: Optimization of parameters for purification.

Recombinant hepatitis B surface antigen (r-HBsAg) produced in yeast is adsorbed on a diatomaceous earth matrix for purification purposes. A pH dependence in the adsorption-elution behavior was found. The capacity of celite (Hyflo Super Cei) for adsorbing r-HBsAg increased with decreasing pH.

Hexosaminidase C in Tay-Sachs and Sandhoff disease.

1. Hexosaminidase C has been purified from human placenta. Complete separation from hexosaminidases A and B was achieved.