Respuesta inmune humoral a cuatro vacunas contra el SARS-CoV-2 en profesionales de la salud

Objetivo: Describir la concentración de los anticuerpos neutralizantes detectados en el suero de profesionales de la salud que recibieron alguna de las vacunas contra el SARS-CoV-2, desarrollada por las empresas Sinopharm, Pfizer, Johnson & Johnson o el candidato vacunal de CureVac. Materiales y métodos: Investigación observacional, descriptiva, retrospectiva, de corte transversal. Se incluyeron en el estudio un total de 217 profesionales de la salud que recibieron el esquema completo de las vacunas de Sinopharm, Pfizer, Johnson & Johnson o del candidato de CureVac. A estos individuos se les había determinado la presencia de anticuerpos neutralizantes contra el SARS-CoV-2 en el suero mediante la técnica de inmunoensayo por electroquimioluminiscencia (eCLIA). Se consideraron las variables edad, sexo, antecedentes de infección con el SARS-CoV-2, concentración de anticuerpos neutralizantes y tipo de vacuna administrada. Resultados: El 16,60 % de los profesionales de la salud manifestó haber tenido COVID-19 antes de haber recibido la vacunación. Ellos se inmunizaron con las vacunas de Sinopharm (74,65 %), Pfizer (12,90 %), Johnson & Johnson (5,07 %) y el candidato de CureVac (7,37 %). Independientemente de la vacuna recibida, el 42,50 % de las personas sin infección previa que recibieron la vacuna no desarrollaron anticuerpos neutralizantes, mientras que el 16,70 % de los que sí tuvieron enfermedad previa no desarrolló estos anticuerpos. La vacuna de Pfizer indujo mayor concentración de anticuerpos neutralizantes (196,27 UA/mL) en pacientes con o sin infección previa. Conclusiones: El estudio confirma que la vacunación refuerza la inmunidad contra el nuevo coronavirus en individuos con diagnóstico previo de COVID-19, y sugiere que la vacuna desarrollada por Pfizer estimula de manera más eficaz la producción de anticuerpos neutralizantes.

Objective: To describe the concentration of neutralizing antibodies in serum from healthcare professionals who received any of the SARS-CoV-2 vaccines developed by Sinopharm, Pfizer or Johnson & Johnson, or CureVac's vaccine candidate. Materials and methods: An observational, descriptive, retrospective, cross-sectional research which included 217 healthcare professionals fully vaccinated with Sinopharm, Pfizer or Johnson & Johnson's vaccines, or CureVac's vaccine candidate. The presence of anti-SARS-CoV-2 neutralizing antibodies in serum was determined in these individuals using the electrochemiluminescence immunoassay (ECLIA). Variables such as age, sex, history of infection with SARS-CoV-2, concentration of neutralizing antibodies and brand of vaccine administered were considered. Results: Sixteen point six zero percent (16.60 %) of the healthcare professionals stated that they had already had COVID-19 before receiving the vaccine. They were immunized with the vaccines developed by Sinopharm (74.65 %), Pfizer (12.90 %) or Johnson & Johnson (5.07 %), or CureVac's vaccine candidate (7.37 %). Regardless of the vaccine received, 42.50 % of the individuals who had not been previously infected with SARS-CoV-2 and 16.70 % of those who had been previously infected did not develop neutralizing antibodies. Pfizer's vaccine produced the highest concentration of neutralizing antibodies (196.27 AU/mL) in patients with or without previous infection. Conclusions: The study demonstrates that vaccination boosts immunity in people previously infected with the novel coronavirus and suggests that Pfizer's vaccine produces the highest concentration of neutralizing antibodies.

The use of convalescent plasma therapy in the management of a pregnant woman with COVID-19: a case report

ABSTRACT The coronavirus disease 19 (COVID-19) is responsible for the current worldwide pandemic. Treatment and prophylaxis are still under investigation. Convalescent plasma therapy could be an alternative. We report a case of a 41-year-old patient, at 28 weeks of gestation, was hospitalized with COVID-19. On the 10th day after onset of symptoms, the clinical picture worsened, and she required high-flow oxygen therapy (30L/minute), with 92% oxygen saturation, and chest X-ray showing mild bilateral opacities at lung bases. Blood tests showed D-dimer 1,004ng/mL, C-reactive protein 81mg/L, pro-calcitonin 0.05ng/mL and interleukine-6 42.9pg/mL. The therapy chosen was Tazocin® 12g/day, vancomycin 2g/day, and methylprednisolone 40mg/day. In addition, convalescent plasma therapy was administered (275mL) uneventfully, including SARS-CoV-2 antibodies and neutralizing antibodies >1:160. The patient had a fast recovery. The early administration of convalescent plasma, with high titers of neutralizing antibodies, may be an alternative option for severe COVID-19 during pregnancy, until further studies demonstrate an efficient and safe treatment or prophylaxis.

Immune characterization of a Colombian family cluster with SARS-CoV-2 infection / Caracterización inmunológica de un grupo familiar colombiano con infección por SARS-CoV-2

Abstract | Introduction: Immunological markers have been described during COVID-19 and persist after recovery. These immune markers are associated with clinical features among SARS- CoV-2 infected individuals. Nevertheless, studies reporting a comprehensive analysis of the immune changes occurring during SARS-CoV-2 infection are still limited. Objective: To evaluate the production of proinflammatory cytokines, the antibody response, and the phenotype and function of NK cells and T cells in a Colombian family cluster with SARS-CoV-2 infection. Materials and methods: Proinflammatory cytokines were evaluated by RT-PCR and ELISA. The frequency, phenotype, and function of NK cells (cocultures with K562 cells) and T-cells (stimulated with spike/RdRp peptides) were assessed by flow cytometry. Anti-SARS-CoV-2 antibodies were determined using indirect immunofluorescence and plaque reduction neutralization assay. Results: During COVID-19, we observed a high proinflammatory-cytokine production and a reduced CD56bright-NK cell and cytotoxic response. Compared with healthy controls, infected individuals had a higher frequency of dysfunctional CD8+ T cells CD38+HLA-DR-. During the acute phase, CD8+ T cells stimulated with viral peptides exhibited a monofunctional response characterized by high IL-10 production. However, during recovery, we observed a bifunctional response characterized by the co-expression of CD107a and granzyme B or perforin. Conclusion: Although the proinflammatory response is a hallmark of SARS-CoV-2 infection, other phenotypic and functional alterations in NK cells and CD8+ T cells could be associated with the outcome of COVID-19. However, additional studies are required to understand these alterations and to guide future immunotherapy strategies.

Resumen | Introducción. Se han descrito diferentes marcadores inmunológicos durante la COVID-19, los cuales persisten incluso después de la convalecencia y se asocian con los estadios clínicos de la infección. Sin embargo, aún son pocos los estudios orientados al análisis exhaustivo de las alteraciones del sistema inmunológico en el curso de la infección. Objetivo. Evaluar la producción de citocinas proinflamatorias, la reacción de anticuerpos, y el fenotipo y la función de las células NK y los linfocitos T en una familia colombiana con infección por SARS-CoV-2. Materiales y métodos. Se evaluaron las citocinas proinflamatorias mediante RT-PCR y ELISA; la frecuencia, el fenotipo y la función de las células NK (en cocultivos con células K562) y linfocitos T CD8+ (estimulados con péptidos spike/RdRp) mediante citometría de flujo, y los anticuerpos anti-SARS-CoV-2, mediante inmunofluorescencia indirecta y prueba de neutralización por reducción de placa. Resultados. Durante la COVID-19 hubo una producción elevada de citocinas proinflamatorias, con disminución de las células NK CD56 bright y reacción citotóxica. Comparados con los controles sanos, los individuos infectados presentaron con gran frecuencia linfocitos T CD8+ disfuncionales CD38+HLA-DR-. Además, en los linfocitos T CD8+ estimulados con péptidos virales, predominó una reacción monofuncional con gran producción de IL-10 durante la fase aguda y una reacción bifuncional caracterizada por la coexpresión de CD107a y granzima B o perforina durante la convalecencia. Conclusión. Aunque la reacción inflamatoria caracteriza la infección por SARS-CoV-2, hay otras alteraciones fenotípicas y funcionales en células NK y linfocitos T CD8+ que podrían asociarse con la progresión de la infección. Se requieren estudios adicionales para entender estas alteraciones y guiar futuras estrategias de inmunoterapia.

Detección de anticuerpos neutralizantes en profesionales de la salud vacunados contra el SARS-CoV-2

Objetivo: Determinar la presencia y concentración de los anticuerpos neutralizantes en el suero de individuos que recibieron la vacuna contra el SARS-CoV-2 desarrollada por la empresa Sinopharm. Materiales y métodos: Investigación descriptiva y transversal. En el estudio se incluyeron 117 profesionales de la salud inoculados con dos dosis de la vacuna Sinopharm, en quienes se había detectado la presencia de anticuerpos neutralizantes contra SARS-CoV-2 en el suero mediante la técnica de inmunoensayo de electroquimioluminiscencia (eCLIA). Las variables consideradas en el estudio fueron la edad, el sexo, la concentración de anticuerpos neutralizantes y el antecedente de haber tenido COVID-19. Resultados: Se evidenció el incremento significativo de la concentración de anticuerpos neutralizantes en las personas que recibieron la vacuna y tuvieron una infección previa por SARS-CoV-2 (p < 0,001) respecto a las que se vacunaron, pero no presentaron infección previa. Conclusiones: El estudio evidencia que la vacunación refuerza la inmunidad contra el nuevo coronavirus en los pacientes con diagnóstico previo de COVID-19 y sugiere la relevancia de la aplicación de una tercera dosis de esta vacuna.

Objective: To describe the presence and the concentration of neutralizing antibodies at serum of healthcare professionals inoculated with the Sinopharm anti-SARS-CoV2 vaccine. Materials and methods: Descriptive and transversal research. A total of 117 healthcare professionals inoculated with two doses of the Sinopharm vaccine having quantitative data of neutralizing antibodies at serum (detected by eCLIA) were included. Age, sex, neutralizing antibodies concentration and previous diagnostic of COVID-19 diseases were the variables. Results: A significant increase on neutralizing antibodies concentration were detected on pre- COVID-19 vaccinated persons regarding those vaccinated without previous diagnostic of the viral infection (p < 0,001). Conclusions: the study evidence that Sinopharm vaccine boost immunity against the new coronavirus on previously infected persons and suggest that a third dose of the vaccine could be relevant to boost the immune response.

Posibles estrategias de tratamiento para COVID-19 / Possible treatment strategies for COVID-19

No hay tratamiento antiviral específico para el COVID-19. Sin embargo, conocimientos adquiridos durante los brotes del SARS y el MERS, en conjunto con la información obtenida con COVID-19, han permitido detectar varios objetivos terapéuticos en el ciclo de replicación del virus, y en su patogénesis. Se incluye la evidencia actual con respecto a los principales tratamientos propuestos para COVID-19, reutilizados o experimentales, mediante una revisión de la literatura científica a la fecha. Debido a la falta de ensayos controlados aleatorios, se incluyeron: informes de casos, series de casos y artículos de revisión. Globalmente se están llevando a cabo múltiples estudios con el fin de identificar agentes que sean efectivos ante COVID-19, en los siguientes objetivos estratégicos: inhibición de la entrada/fusión del virus (anticuerpos neutralizantes, inhibidores de proteasa de serina transmembrana 2, cloroquina, hidroxicloroquina y umifenovir); interrupción de la replicación viral (remdesivir, favipiravir, lopinavir/ritonavir e ivermectina) y supresión de la respuesta inflamatoria excesiva (corticosteroides, tocilizumab, e inmunoglobulina). Aún no existe un tratamiento efectivo y seguro contra COVID-19; los fármacos descritos en esta revisión se administran como uso compasivo de drogas, o bien, como parte de un ensayo clínico. La terapia de soporte continúa siendo el pilar del manejo de COVID-19.(AU)

There is no specific antiviral treatment for COVID-19. However, knowledge acquired during the SARS and MERS outbreaks, together with the information obtained with COVID-19, have allowed the detection of various therapeutic targets in the virus replication cycle, and in its pathogenesis. The current evidence regarding the leading treatments proposed for COVID-19, reused or experimental, is included through a review of the scientific literature to date. Due to the lack of randomized controlled trials, the following were involved: case reports, case series and review articles. Globally, multiple studies are being carried out in order to identify agents that are effective against COVID-19, upon the following strategic objectives: inhibition of viral entry/fusion (neutralizing antibodies, transmembrane serine protease 2 inhibitors, chloroquine, hydroxychloroquine, and umifenovir); interruption of viral replication (remdesivir, favipiravir, lopinavir/ritonavir and ivermectin), and suppression of excessive inflammatory response (corticosteroids, tocilizumab, and immunoglobulin). There is still no effective and safe treatment against COVID-19; the medications described in this review are given as compassionate drug use, or as part of a clinical trial. Support therapy continues to be COVID-19 management cornerstone.(AU)

Evaluation of Protective Immunity of Peptide Vaccines Composed of a 15-mer N-terminal Matrix Protein 2 and a Helper T-Cell Epitope Derived from Influenza A Virus

The matrix protein 2 of influenza A virus (IFAV) has a relatively conserved ectodomain (M2e) composed of 23 amino acids, and M2e-based vaccines have been suggested to induce broad protective immunity in mice. In this study, we investigated whether N-terminal sequence of M2e (nM2e)-based vaccines with more conserved nM2e could induce influenza viral neutralizing activity. We constructed linear peptide vaccines with an nM2e sequence for PR8 virus (nM2Pr) connected to a probable 17-mer IFAV-derived helper T-cell epitope (ThE: T1, T2, or T3) at its N- or C-terminus. The peptide vaccines induced significant production of nM2e Abs regardless of either type or location of the ThE-epitope in BALB/c mice, while only T3 was effective in C57BL/6 mice. The Abs against nM2Pr-T3 elicited broader binding affinities to the nM2e peptides derived from various IFAVs than those against T3-nM2Pr. In addition, the nM2e-based vaccines efficiently protected the immunized mice from the lethal challenge of PR8 virus. These results suggest that the more conserved nM2e without cysteine will be useful for development of universal peptide vaccines than M2e.

Antibodies to Interferon beta in Patients with Multiple Sclerosis Receiving CinnoVex, Rebif, and Betaferon

Treatment with interferon beta (IFN-beta) induces the production of binding antibodies (BAbs) and neutralizing antibodies (NAbs) in patients with multiple sclerosis (MS). NAbs against IFN-beta are associated with a loss of IFN-beta bioactivity and decreased clinical efficacy of the drug. The objective of this study was to evaluate the incidence and the prevalence of binding antibodies (BAbs) and neutralizing antibodies (NAbs) to IFN-beta in MS patients receiving CinnoVex, Rebif, or Betaferon. The presence of BAbs was studied in serum samples from 124 MS patients using one of these IFN-beta medications by ELISA. The NAbs against IFN-beta were measured in BAb-positive MS patients receiving IFN-beta using an MxA gene expression assay (real-time RT-PCR). Of the 124 patients, 36 (29.03%) had BAbs after at least 12 months of IFN-beta treatment. The proportion of BAb+ was 38.1% for Betaferon, 21.9% for Rebif, and 26.8% for CinnoVex. Five BAb-positive MS patients were lost to follow-up; thus 31 BAb-positive MS patients were studied for NAbs. NAbs were present in 25 (80.6%) of BAb-positive MS patients receiving IFN-beta. In conclusion, the three IFN-beta preparations have different degrees of immunogenicity.

Screening of HIV-1 neutralizing antibody mimotopes in slow progressor from phage display peptide library / 中华检验医学杂志

ObjectiveTo screen mimetic HIV-1 neutralizing epitopes from plasma with high level neutralizing antibody,and to provide useful information for further study of the interaction between antigen and antibody.MethodsIn order to gain neutralizing antibody recognized mimotopes, we detected neutralizing antibodieslevelsof 11HIV-1infectedslowprogressorsbyPBMC-basedneutralization assays.High-titer HIV-neutralizing antibodies from plasma of SPs was used as the ligand for biopanning by phage-displayed random peptide library.Positive phage clones was evaluated by ELISA,sequenced,and analyzed for homology to HIV-1 env by local BLAST to deduce the neutralizing peptide.ResultsTwenty-two clones were obtained consistent with requirement through three rounds biopanning.After comparison analysis,twelve clones include C8 were obtained as mimotopes of neutralizing antibody,C40 located in gp41Ⅱ cluster with the highest titer by inhibition ratio may be as neutralizing epitope.Conclusion By the use of IgG antibodies from SPs to screen the phage random polypeptide library,one can acquire multiple phage mimetic peptides of HIV related antigen epitope.(Chin J Lab Med,2012,35:838-842 )