136 research outputs found
NS3 genomic sequencing and phylogenetic analysis as alternative to a commercially available assay to reliably determine hepatitis C virus subtypes 1a and 1b
Objective: To evaluate the use of hepatitis C virus (HCV) NS3 sequencing as alternative to the comercially available Versant HCV 2.0 reverse hybridization line-probe assay (LiPA 2.0) to determine HCV genotype 1 (HCV-1) subtypes. Patients and methods: A cohort of 104 patients infected by HCV-1 according to LiPA 2.0 was analyzed in a cross-sectional study conducted in patients seen from January 2012 to June 2016 at an outpatient clinic in Buenos Aires, Argentina. Results: The samples were included within well supported subtype clades: 64 with HCV-1b and 39 with HCV-1a infection. Twenty of the HCV-1a infected patientes were included in a supported sub-clade â1â and 19 individuals were among the basal sub-clade â2â. LiPA 2.0 failed to subtype HCV-1 in 20 (19.2%) individuals. Subtype classification determined by NS3 direct sequencing showed that 2/18 (11.1%) of the HCV-1a-infected patients as determined by LiPA 2.0 were in fact infected by HCV-1b. Of the HCV-1b-infected according to LiPA 2.0, 10/66 (15.2%) patients showed HCV-1a infection according to NS3 sequencing. Overall misclassification was 14.3% (Îș-index for the concordance with NS3 sequencing = 0.635). One (1%) patient was erroneously genotyped as HCV-1 and was revealed as HCV genotype 4 infection. Conclusions: Genomic sequencing of the HCV NS3 region represents an adequate alternative since it provides reliable genetic information. It even distinguishes between HCV-1a clades related to resistance-associated substitutions to HCV protease inhibitors, it provides reliable genetic information for genotyping/subgenotyping and simultaneously allows to determine the presence of resistance-associated substitutions to currently recommended DAAs.Fil: Neukam, Karin. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica; Argentina. Universidad de Sevilla; España. Hospital Universitario de Valme; EspañaFil: MartĂnez, Alfredo P.. Centro de EducaciĂłn MĂ©dica e Investigaciones ClĂnicas âNorberto Quirnoâ; ArgentinaFil: Culasso, AndrĂ©s Carlos Alberto. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica; ArgentinaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones MĂ©dicas e Investigaciones ClĂnicas "Norberto Quirno". CEMIC-CONICET.; ArgentinaFil: GarcĂa, Gabriel. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica; ArgentinaFil: Di Lello, Federico Alejandro. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica; Argentin
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 CientĂficas y TĂ©cnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; ArgentinaFil: Ridruejo, Ezequiel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones MĂ©dicas e Investigaciones ClĂnicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: MartĂnez, Alfredo P.. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones MĂ©dicas e Investigaciones ClĂnicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: PĂ©rez, Paula Soledad. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; ArgentinaFil: Campos, Rodolfo Hector. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; Argentin
Phylogenetic analysis of SARSâCoVâ2 in the first few months since its emergence
During the first months of SARSâCoVâ2 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 SARSâCoVâ2.The molecular evolution in nine genomic regions of SARSâCoVâ2 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 SARSâCoVâ2 evolutionary rate for regions nsp3 and S, the ones presenting greater variability, was estimated as 1.37 x 10â3 and 2.19 x 10â3 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, MatĂas J.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; ArgentinaFil: Mojsiejczuk, Laura Noelia. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay; ArgentinaFil: MartĂnez, Alfredo P.. Centro de Educaciones MĂ©dicas e InvestigaciĂłn ClĂnica "Norberto Quirno"; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; ArgentinaFil: GarcĂa, Gabriel Hugo. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn 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 Ă 10â3 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 CientĂficas y TĂ©cnicas; 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 CientĂficas y TĂ©cnicas; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; ArgentinaFil: MartĂnez, Alfredo P.. Centro de EducaciĂłn MĂ©dica e Investigaciones ClĂnicas "Norberto Quirno"; ArgentinaFil: BarĂ©, Patricia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: GarcĂa, 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 CientĂficas y TĂ©cnicas; Argentin
High Prevalence of Hepatitis C Virus Genotype 1b Infection in a Small Town of Argentina. Phylogenetic and Bayesian Coalescent Analysis
Previous studies in Argentina have documented a general prevalence of Hepatitis C Virus (HCV) infection close to 2%. In addition, a high prevalence of HCV has been recently reported in different Argentinean small rural communities. In this work, we performed a study aimed at analyzing the origins and diversification patterns of an HCV outbreak in Wheelwright, a small rural town located in Santa Fe province (Argentina)
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 BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay; ArgentinaFil: MartĂnez, Alfredo P.. Centro de EducaciĂłn MĂ©dica e Investigaciones ClĂnicas "Norberto Quirno"; ArgentinaFil: Isaac, Katia. Centro de EducaciĂłn MĂ©dica e Investigaciones ClĂnicas "Norberto Quirno"; ArgentinaFil: Laham, Gustavo. Centro de EducaciĂłn MĂ©dica e Investigaciones ClĂnicas "Norberto Quirno"; ArgentinaFil: Ridruejo, Ezequiel. Centro de EducaciĂłn MĂ©dica e Investigaciones ClĂnicas "Norberto Quirno"; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: GarcĂa, Gabriel Hugo. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn 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 ÂĄĂ10 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 (23šC43); 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 BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Blejer, Jorgelina L.. FundaciĂłn Hemocentro; ArgentinaFil: Alter, Adriana. FundaciĂłn Hemocentro; ArgentinaFil: Bartoli, Sonia. Centro Regional de Hemoterapia Jujuy; ArgentinaFil: Vargas, Fabiana Alejandra. Centro Regional de Hemoterapia de Mendoza; ArgentinaFil: Ruiz, RosĂĄngela. Hospital Regional Rio Grande; ArgentinaFil: Galli, Claudio. Hospital Regional Rio Grande; ArgentinaFil: Blanco, Sebastian. Universidad Nacional de CĂłrdoba. Facultad de Medicina; Argentina. FundaciĂłn Banco Central de Sangre; ArgentinaFil: Gallego, Sandra Veronica. FundaciĂłn Banco Central de Sangre; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Medicina; ArgentinaFil: FernĂĄndez, Roberto. FundaciĂłn Hemocentro; ArgentinaFil: MartĂnez, Alfredo P.. Centro de EducaciĂłn MĂ©dica e Investigaciones ClĂnicas "Norberto Quirno"; ArgentinaFil: Flichman, Diego Martin. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones BiomĂ©dicas en Retrovirus y Sida; Argentin
Structural insight into the TFIIEâTFIIH interaction: TFIIE and p53 share the binding region on TFIIH
RNA polymerase II and general transcription factors (GTFs) assemble on a promoter to form a transcription preinitiation complex (PIC). Among the GTFs, TFIIE recruits TFIIH to complete the PIC formation and regulates enzymatic activities of TFIIH. However, the mode of binding between TFIIE and TFIIH is poorly understood. Here, we demonstrate the specific binding of the C-terminal acidic domain (AC-D) of the human TFIIEα subunit to the pleckstrin homology domain (PH-D) of the human TFIIH p62 subunit and describe the solution structures of the free and PH-D-bound forms of AC-D. Although the flexible N-terminal acidic tail from AC-D wraps around PH-D, the core domain of AC-D also interacts with PH-D. AC-D employs an entirely novel binding mode, which differs from the amphipathic helix method used by many transcriptional activators. So the binding surface between PH-D and AC-D is much broader than the specific binding surface between PH-D and the p53 acidic fragments. From our in vitro studies, we demonstrate that this interaction could be a switch to replace p53 with TFIIE on TFIIH in transcription
Una rica colección de bacterias marinas antårticas (Caleta Potter, islas Shetlands del Sur) revela diversos filotipos endémicos y previamente no descritos
La riqueza bacteriana de la AntĂĄrtida marĂtima ha sido pobremente descripta hasta la actualidad. En este trabajo se estudiĂł la filogenia de un grupo de colecciones bacterianas planctĂłnicas obtenidas de agua de mar de tres localizaciones cercanas a la base cientĂfica argentina antĂĄrtica Jubany (actualmente Carlini). Sesenta secuencias clonadas del ARN 16S fueron agrupadas filogenĂ©ticamente en las clases Alfaproteobacteria (30/60 clones), Gammaproteobacteria (19/60 clones), Betaproteobacteria (2/60) y Cytophaga?Flavobacteriia?Bacteroides [CFB (3 / 60)]. Por otro lado, seis de las sesenta secuencias (6/60) no pudieron ser clasificadas en ningĂșn grupo conocido. Tanto las Alfaproteobacteria como las Gammaproteobacteria mostraron secuencias no descriptas con anterioridad y eventualmente endĂ©micas. TambiĂ©n es remarcable la ausencia de Cyanobacteria en esta biblioteca. En conclusiĂłn, estamos publicando aquĂ una rica colecciĂłn de secuencias bacterianas de origen marino compuesta por una mayorĂa de secuencias ampliamente divergentes entre sĂ y tambiĂ©n distantes de aquellas mĂĄs intimamente relacionadas dentro de las depositadas hasta el presente en los bancos de datos.Fil: Landone Vescovo, Ignacio A.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; ArgentinaFil: Golemba, Marcelo DarĂo. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Di Lello, Federico Alejandro. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Culasso, AndrĂ©s Carlos Alberto. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de VirologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Levin, Gustavo. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de MicrobiologĂa Industrial y BiotecnologĂa; ArgentinaFil: Ruberto, Lucas Adolfo Mauro. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. DirecciĂłn Nacional del AntĂĄrtico. Instituto AntĂĄrtico Argentino; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de MicrobiologĂa Industrial y BiotecnologĂa; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Mac Cormack, Walter P.. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de MicrobiologĂa, InmunologĂa y BiotecnologĂa. CĂĄtedra de MicrobiologĂa Industrial y BiotecnologĂa; Argentina. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. DirecciĂłn Nacional del AntĂĄrtico. Instituto AntĂĄrtico Argentino; ArgentinaFil: LĂłpez, JosĂ© L.. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Departamento de MicrobiologĂa. CĂĄtedra de VirologĂa; Argentin
Assessment of the humoral response to the homologous Gam-COVID-Vac (Sputnik V) or heterologous Sputnik V/mRNA-1273 (Moderna) vaccination against SARS-CoV-2 in dialysis patients
Background and Aim
Dialysis patients are a high-risk population and have a reduced immune response to vaccination against SARS-CoV-2. The aim of this study was to assess the humoral response to homologous Gam-COVID-Vac (Sputnik V) and heterologous Sputnik V/mRNA-1273 (Moderna) vaccination in dialysis patients. The vaccination scheme depended on dose availability and the prioritization of risk populations as established by the Argentine Ministry of Health.
Methods
Previous COVID-19 infection was determined in symptomatic patients. Binding IgG antibodies against the spike (S) receptor-binding domain (RBD) of SARS-CoV-2 (anti-S-RBD) concentration was assessed between 3 and 16 weeks after the boost dose. Anti-S-RBD antibodies were quantified using the Abbott Diagnostics SARS-CoV-2 IgG II Quant chemiluminescent microparticle immunoassay (CMIA) on an Architect i2000 SR and an Alinity I analyzer (Abbott Diagnostics, Abbott Park, Illinois, USA). To standardize the results to WHO binding antibody units (BAU), a correction factor for Abbott arbitrary units (AU) was applied where 1 BAU/mL equals 0.142 AU, as previously established by Abbott with the WHO international standard NIBSC 20â136. Following the manufacturerâs recommendations, samples were considered reactive for anti-S-RBD when titers were above 50 AU/mL (7.2 BAU/mL). An 80% protective effect (PROT-80) against symptomatic SARS-CoV-2 infection was assumed when anti-S-RBD titers were 506 BAU/ml or higher. Charlson Comorbidity Index (CCI) score was classified as mildâ=â1â2, moderateâ=â3â4, and severeââ„â5. Side effects were evaluated until day 7 by patientsÂŽ self-reported questionnaire.
Results
One hundred seven participants were enrolled [nâ=â84 homologous (SpV/SpV), nnâ23 heterologous (SpV/Mod)]. Median (IQR) age was 64 (50â75) years old and 79 (73.8%) were male. Additionally, 19 (22.6%) of the SpV/SpV and 4 (17.4%) of the SpV/Mod group had a prior confirmed SARS-CoV-2 infection (pâ=â0.589). In the overall population, 103 patients reached seroconversion (96.3%). Anti-S-RBD IgG median titers (IQR) were higher in the heterologous [1222 (288â5680) BAU/mL] than in the homologous scheme [447 (100â1551) BAU/mL], pâ=â0.022. In a linear model adjusted for age, gender, days from first vaccination to boost dose and days from the boost dose to the anti-S-RBD IgG determination, previous SARS-COV-2 infection (B: 2062.2; CI95: 1231.8â2892.6; pâ<â0.001), and SpV/Mod vaccination scheme (B: 1294.6; CI95: 435.58â2147.6; pâ=â0.003) were independently associated with anti-S-RBD levels. Finally, a higher frequency of adverse effects was associated with the heterologous scheme, although they were well tolerated by all individuals.
Conclusions
The present study provides evidence that the homologous SpV/SpV and heterologous SpV/Mod schemes showed good efficacy and safety in patients on chronic dialysis. These results could be useful for designing future vaccination strategies, especially aimed at this risk group.FAD is a member of the National Research Council (CONICET) Research Career Program. K.N. is the recipient of a Miguel Servet contract by the Instituto de Salud Carlos III (grant number CPII18/00033). We would like to thank Mrs. Silvina Heisecke, from CEMICâCONICET, for the copyediting of the manuscriptPeer reviewe
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