Insights into induction of the immune response by the hepatitis B vaccine

After more than four decades of hepatitis B virus (HBV) vaccine implementation, its safety and efficacy in preventing HBV infection have been proven and several milestones have been achieved. Most countries have included HBV immunization schedules in their health policies and progress has been made regarding universalization of the first HBV vaccine dose at birth. All of these actions have significantly contributed to reducing both the incidence of HBV infection and its related complications. However, there are still many drawbacks to overcome. The main concerns are the deficient coverage rate of the dose at birth and the large adult population that has not been reached timely by universal immunization. Additionally, the current most widely used second-generation vaccines do not induce protective immunity in 5% to 10% of the population, particularly in people over 40-years-old, obese (body mass index > 25 kg/m2), heavy smokers, and patients undergoing dialysis or infection with human immunodeficiency virus. Recently developed and approved novel vaccine formulations using more potent adjuvants or multiple antigens have shown better performance, particularly in difficult settings. These advances re-launch the expectations of achieving the World Health Organization’s objective of completing hepatitis control by 2030.Fil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Martínez, Alfredo Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentin

Hepatitis C virus treatment failure: Clinical utility for testing resistance-associated substitutions

The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions (RAS). However, the consequence of resistance selection during new direct-acting antiviral drug (DAA) treatment is not necessarily the therapeutic failure. In fact, DAA treatment has shown a high rate (> 95%) of sustained virological response even when high baseline RAS prevalence has been reported. In the context of RAS emergence and high rates of sustained viral response, the clinical relevance of variants harboring RAS is still controversial. Therefore, in order to summarize the data available in international guidelines, we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.Fil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Pereson, Matías Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Investigaciones en Bacteriología y Virología Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

The impact of sovereign credit risk on bank funding conditions

The financial crisis and the ensuing recession have caused a sharp deterioration in public finances across advanced economies, raising investor concerns about sovereign risk. The concerns have so far mainly affected the euro area, where some countries have seen their credit ratings downgraded during 2009−11 and their funding costs rise sharply. Other countries have also been affected, but to a much lesser extent. Greater sovereign risk is already having adverse effects on banks and financial markets. Looking forward, sovereign risk concerns may affect a broad range of countries. In advanced economies, government debt levels are expected to rise over coming years, due to high fiscal deficits and rising pension and health care costs. In emerging economies, vulnerability to external shocks and political instability may have periodic adverse effects on sovereign risk. Overall, risk premia on government debt will likely be higher and more volatile than in the past. In some countries, sovereign debt has already lost its risk-free status; in others, it may do so in the future. The challenge for authorities is to minimise the negative consequences for bank funding and the flow-on effects on the real economy. This report outlines the impact of sovereign risk concerns on the cost and availability of bank funding over recent years. It then describes the channels through which sovereign risk affects bank funding. The last section summarises the main conclusions and discusses some implications for banks and the official sector. Two caveats are necessary before discussing the main findings. First, the analysis focuses on causality going from sovereigns to banks, as is already the case in some countries, and, looking forward, is a possible scenario for other economies. But causality may clearly also go from banks to sovereigns. However, even in this second case, sovereign risk eventually acquires its own dynamics and compounds the problems of the banking sector. Second, the report examines the link between sovereign risk and bank funding in general terms, based on recent experience and research. It does not assess actual sovereign risk and its impact on bank stability in individual countries at the present juncture.Sovereign debt; banks; financial turmoil

Molecular epidemiology of hepatitis B virus mutants associated with vaccine-escape, drug-resistance and diagnosis failure

The massive implementation of the vaccine and antiviral agents against hepatitis B virus (HBV), targeting the envelope and viral polymerase genes, induces a selection pressure that might lead to the emergence of variants that impair the effectiveness of the vaccine, diagnostic methods and antiviral therapy. The aim of this study was to evaluate the prevalence of HBV vaccine escape mutants (VEMs), diagnostic failure mutants (DFMs) and treatment resistance mutants (ARMs) among individuals from Buenos Aires, Argentina. HBV surface antigen and polymerase sequences obtained from serum samples of 530 HBV-infected individuals were analysed. Samples belonged to genotypes A (28.1%), D (13.6%) and F (58.3%). VEMs, DMFs and ARMs were present in 40 (7.5%), 57 (10.7%) and 27 (5.1%) samples within the studied population. Additionally, eight nonpreviously reported VEMs and nine DFMs were identified. VEMs and DFMs were biased by genotype, being higher in genotype D (33.3% and 33.3%) compared to genotype A (6% and 17.4%) and genotype F (2.3% and 2.3%) (P > 0.001). On the contrary, there was no association between the presence of ARMs and HBV genotype (P = 0.324). VEMs, DFMs and ARMs create public health concerns. The current study provided valuable information about mutants in surface antigen and polymerase in HBV-infected patients from Argentina where HBV-F is the most prevalent genotype. Consequently, it constitutes an important reference for Latin American clinicians in order to optimize the management of HBV-infected patients.Fil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Martínez, Alfredo P.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Pérez, Paula Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Phylogenetic analysis of SARS‐CoV‐2 in the first few months since its emergence

During the first months of SARS‐CoV‐2 evolution in a new host, contrasting hypotheses have been proposed about the way the virus has evolved and diversified worldwide. The aim of this study was to perform a comprehensive evolutionary analysis to describe the human outbreak and the evolutionary rate of different genomic regions of SARS‐CoV‐2.The molecular evolution in nine genomic regions of SARS‐CoV‐2 was analyzed using three different approaches: phylogenetic signal assessment, emergence of amino acid substitutions, and Bayesian evolutionary rate estimation in eight successive fortnights since the virus emergence.All observed phylogenetic signals were very low and tree topologies were in agreement with those signals. However, after four months of evolution, it was possible to identify regions revealing an incipient viral lineage formation despite the low phylogenetic signal, since fortnight 3. Finally, the SARS‐CoV‐2 evolutionary rate for regions nsp3 and S, the ones presenting greater variability, was estimated as 1.37 x 10‐3 and 2.19 x 10‐3 substitution/site/year, respectively.In conclusion, results from this work about the variable diversity of crucial viral regions and determination of the evolutionary rate are consequently decisive to understand essential features of viral emergence. In turn, findings may allow the first time characterization of the evolutionary rate of S protein, crucial for vaccine development.Fil: Pereson, Matías J.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Mojsiejczuk, Laura Noelia. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Martínez, Alfredo P.. Centro de Educaciones Médicas e Investigación Clínica "Norberto Quirno"; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: García, Gabriel Hugo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Evolutionary analysis of SARS-CoV-2 spike protein for its different clades

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the main target for antiviral and vaccine development. Despite its relevance, e information is scarse about its evolutionary traces. The aim of this study was to investigate the diversification patterns of the spike for each clade of SARS-CoV-2 through different approaches. Two thousand and one hundred sequences representing the seven clades of the SARS-CoV-2 were included. Patterns of genetic diversifications and nucleotide evolutionary rate were estimated for the spike genomic region. The haplotype networks showed a star shape, where multiple haplotypes with few nucleotide differences diverge from a common ancestor. Four hundred seventy-nine different haplotypes were defined in the seven analyzed clades. The main haplotype, named Hap-1, was the most frequent for clades G (54%), GH (54%), and GR (56%) and a different haplotype (named Hap-252) was the most important for clades L (63.3%), O (39.7%), S (51.7%), and V (70%). The evolutionary rate for the spike protein was estimated as 1.08 × 10−3 nucleotide substitutions/site/year. Moreover, the nucleotide evolutionary rate after nine months of the pandemic was similar for each clade. In conclusion, the present evolutionary analysis is relevant as the spike protein of SARS-CoV-2 is the target for most therapeutic candidates; besides, changes in this protein could have consequences on viral transmission, response to antivirals and efficacy of vaccines. Moreover, the evolutionary characterization of clades improves knowledge of SARS-CoV-2 and deserves to be assessed in more detail as re-infection by different phylogenetic clades has been reported.Fil: Pereson Moschen, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Martínez, Alfredo P.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Baré, Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: García, Gabriel Hugo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquimica. Instituto de Investigaciones En Bacteriologia y Virologia Molecular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Seroprevalence of hepatitis B, hepatitis C and HIV infection among patients undergoing haemodialysis in Buenos Aires, Argentina

Introduction. Blood-borne infections are a major cause of harm in individuals on haemodialysis (HD). In particular, knowledge about hepatitis B (HBV), hepatitis C (HCV) and human immunodeficiency virus (HIV) status in HD patients is a major concern, since these infections may cause comorbidities in this setting. There is a paucity of data regarding this issue in Argentina. Hypothesis/Gap Statement. The epidemiological surveillance of HBV, HCV, and HIV is a fundamental tool for planning and implementing health strategies in order to prevent and control viral transmission of these viral agents. Aim. To determine the seroprevalence of HBV, HCV and HIV infections in HD patients in Buenos Aires, Argentina. Methodology. Seven hundred and forty-eight HD patients were included in a retrospective cross-sectional study. Serological assays were performed to determine HBV, HCV and HIV status. HBV HBsAg and anti-HBc IgG were analysed using AxSYM (samples before 2010) or the Architect Abbott system (samples since 2010), anti-HCV IgG testing was performed using the anti-HCV enzyme immunoassay AxSYM HCV V3.0 and ARCHITECT anti-HCV, while HIV was tested for using AxSYM HIV 1/2 gO and ARCHITECT HIV Ag/Ab Combination. HCV genotyping was carried out by phylogenetic analysis of the NS5B partial gene. Results. Infection with one of the viruses was detected in 31.1% of patients [HBV in 82 (11.0%), HCV in 179 (23.9%) and HIV in 6 (0.8%)]. Thirty-two (4.3%) patients had 2 virus markers [27 (3.6%) with HCV/HBV, 4 (0.5%) with HCV/HIV and 1 (0.13%) with HBV/HIV]. Finally, a single patient (0.13%) presented all three markers. Time on dialysis was correlated with HCV but not with HBV infection. The HCV subtype distribution in HD patients was inverted with respect to that observed in the general population (HCV-1a 73.2% and HCV-1b 26.8% in HD vs HCV-1a 26.5% and HCV-1b 73.5% in the general population, P <0.001). Conclusion. Despite the implementation of universal precautionary biosafety standards for dialysis, infection with HBV and HCV continues to occur at very high rates in HD patients. The results emphasize the need to carry out proactive tasks for early diagnosis and treatment of infected individuals and to vaccinate those with non-protective antiHBs antibodies in order to reduce morbidity and mortality in HD patients.Fil: Pereson Moschen, Matias Javier. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Martínez, Alfredo P.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Isaac, Katia. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Laham, Gustavo. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Ridruejo, Ezequiel. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: García, Gabriel Hugo. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Hepatitis B surface antibodies seroprevalence among people born before and after implementation of universal HBV vaccination

Universal vaccination is the most effective strategy to control hepatitis B virus (HBV) infection. In Argentina, vaccination against HBV was incorporated in year 2000 for newborns and in 2003 for 11 years old children. However, there is a paucity of data about protection levels against HBV infection. The aim of this work was to determine the prevalence of seroprotective anti-HBs antibodies (aHBs) in Argentina. Serum samples negative for HBsAg and anti-HBc from 132 children born after year 2000 and 762 blood donors, older than 18 years, from five centers across the country, were analyzed for aHBs. Titers ¡Ý10 mIU/mL were observed in 74/132 children (56.1%) and 336/762 (44.1%) in blood donors. The median age for blood donors was 33.9 (23¨C43); from them, 210 (27.6%) were born after 1992 and, therefore, were catch-up by vaccine implementation at 11 years old age. Donors born in 1992 or before showed a significantly lower frequency of protection (32.2%) compared to donors born after 1992 (75.2%), p < 0.0001. In addition, significant differences were observed in the status of seroprotection between different participating centers (p = 0.024). Implementation of HBV vaccine in 2000 and 2003 implied an overall increase of the aHBs seroprotective rates, with a particularly adequate response in children vaccinated at 11 years old age. The observed results suggest that population born in 1992 or before is currently the most susceptible. Consequently, it would be advisable to become aware of the risk of transmission in this age group and to stress this population vaccination campaigns.Fil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Blejer, Jorgelina L.. Fundación Hemocentro; ArgentinaFil: Alter, Adriana. Fundación Hemocentro; ArgentinaFil: Bartoli, Sonia. Centro Regional de Hemoterapia Jujuy; ArgentinaFil: Vargas, Fabiana Alejandra. Centro Regional de Hemoterapia de Mendoza; ArgentinaFil: Ruiz, Rosángela. Hospital Regional Rio Grande; ArgentinaFil: Galli, Claudio. Hospital Regional Rio Grande; ArgentinaFil: Blanco, Sebastian. Universidad Nacional de Córdoba. Facultad de Medicina; Argentina. Fundación Banco Central de Sangre; ArgentinaFil: Gallego, Sandra Veronica. Fundación Banco Central de Sangre; Argentina. Universidad Nacional de Córdoba. Facultad de Medicina; ArgentinaFil: Fernández, Roberto. Fundación Hemocentro; ArgentinaFil: Martínez, Alfredo P.. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

TAMs PD-L1(+) in the reprogramming of germ cell tumors of the testis

Background: In recent years, several studies focused on the process of reprogramming of seminoma (S) cells, which regulates the transition from pure S (P-S) to S component (S-C) of mixed germ cell tumors of the testis (GCTT) and finally to embryonal carcinoma (EC) and other nonseminomatous GCTT (NS-GCTT). The accepted pathogenetic model is driven and regulated by cells (macrophages, B- and T-lymphocytes) and molecules of the tumor microenvironment (TME). Herein, we tested a series of GCTT with double staining (DS) for CD68-PD-L1 to evaluate tumor-associated macrophages (TAMs) expressing programmed death-ligand 1 (PD-L1) [TAMs PD-L1(+)] and clarify if these cells may be involved in establishing the fate of GCTT. Methods: We collected 45 GCTT (comprising a total of 62 different components of GCTT). TAMs PD-L1(+) were evaluated with three different scoring systems [TAMs PD-L1(+)/mm2, TAMs PD-L1(+)/mm2H-score, TAMs PD-L1(+) %], and compared using pertinent statistic tests (Student's t-test and Mann-Whitney U test). Results: We found that TAMs PD-L1(+) values were higher in S rather than EC (p&nbsp;=&nbsp;0.001, p&nbsp;=&nbsp;0.015, p&nbsp;=&nbsp;0.022) and NS-GCTT (p&nbsp;&lt;&nbsp;0.001). P-S showed statistically significant differences in TAMs PD-L1(+) values compared to S-C (p&nbsp;&lt;&nbsp;0.001, p&nbsp;=&nbsp;0.006, p&nbsp;=&nbsp;0.015), but there were no differences between S-C and EC (p&nbsp;=&nbsp;0.107, p&nbsp;=&nbsp;0.408, p&nbsp;=&nbsp;0.800). Finally, we found statistically significant differences also in TAMs PD-L1(+) values between EC and other NS-GCTT (p&nbsp;&lt;&nbsp;0.001). Conclusions: TAMs PD-L1(+) levels gradually decrease during the reprogramming of S cells {P-S [(high values of TAMs PD-L1(+)] → S-C and EC [(intermediate values of TAMs PD-L1(+)] → other NS-GCTT [(low values of TAMs PD-L1(+)], supporting a complex pathogenetic model where the interactions between tumor cells and TME components [and specifically TAMs PD-L1(+)] play a key role in determining the fate of GCTT