Vaccines against monkeypox.

The monkeypox virus is a virus that has 90% genomic homology with the human (smallpox), but it is naturally transmitted between different wild animal reservoirs and is considered a zoonosis. Throughout the 20th century, different vaccines based on the vaccinia poxvirus were developed and used for vaccination against smallpox. After the eradication of smallpox, these vaccines were no longer used. Current vaccines against monkeypox virus are classified by the WHO as replicative (ACAM2000), minimally replicative (LC16m8) and non-replicative (MVA-BN), the latter being the one currently used. The 2022 extra-African monkeypox virus epidemic has highlighted the lack of vaccines with proven efficacy and low reactogenicity. It is considered that the use of this vaccine in the current outbreak may play a role in the prevention or attenuation of the disease as pre-exposure prophylaxis in close contacts of confirmed cases.

El virus de la viruela de los monos es un virus que presenta un 90% de homología genómica con el humano (smallpox), pero se trasmite de forma natural entre diferentes reservorios animales salvajes y es considerado una zoonosis. A lo largo del siglo XX se desarrollaron diferentes vacunas basadas en el poxvirus vaccinia que fueron utilizadas para la vacunación frente a la viruela humana. Tras la erradicación de la viruela humana estas vacunas dejaron de utilizarse. Las vacunas actuales frente a la viruela de los monos se clasifican por la OMS como replicativas (ACAM2000), mínimamente replicativas (LC16m8) y no replicativas (MVA-BN), siendo esta última la utilizada en la actualidad. La epidemia extraafricana de viruela de los monos de 2022 ha puesto en evidencia la falta de vacunas de eficacia demostrada y de baja reactogenicidad. Se considera que la utilización de esta vacuna en el brote actual puede desempeñar un papel en la prevención o atenuación de la enfermedad como profilaxis preexposición en contactos estrechos de casos confirmados.

Vacunas frente a la viruela del mono (monkeypox) / Vaccines against monkeypox

El virus de la viruela de los monos es un virus que presenta un 90% de homología genómica con el humano (smallpox), pero se trasmite de forma natural entre diferentes reservorios animales salvajes y es considerado una zoonosis. A lo largo del siglo XX se desarrollaron diferentes vacunas basadas en el poxvirus vaccinia que fueron utilizadas para la vacunación frente a la viruela humana. Tras la erradicación de la viruela humana estas vacunas dejaron de utilizarse. Las vacunas actuales frente a la viruela de los monos se clasifican por la OMS como replicativas (ACAM2000), mínimamente replicativas (LC16m8) y no replicativas (MVA-BN), siendo esta última la utilizada en la actualidad. La epidemia extraafricana de viruela de los monos de 2022ha puesto en evidencia la falta de vacunas de eficacia demostrada y de baja reactogenicidad. Se considera que la utilización de esta vacuna en el brote actual puede desempeñar un papel en la prevención o atenuación de la enfermedad como profilaxis preexposición en contactos estrechos de casos confirmados. (AU)

The monkeypox virus is a virus that has 90% genomic homology with the human (smallpox), but it is naturally transmitted between different wild animal reservoirs and is considered a zoonosis. Throughout the 20th century, different vaccines based on the vaccinia poxvirus were developed and used for vaccination against smallpox. After the eradication of smallpox, these vaccines were no longer used. Current vaccines against monkeypox virus are classified by the WHO as replicative (ACAM2000), minimally replicative (LC16m8) and non-replicative (MVA-BN), the latter being the one currently used. The 2022 extra-African monkeypox virus epidemic has highlighted the lack of vaccines with proven efficacy and low reactogenicity. It is considered that the use of this vaccine in the current outbreak may play a role in the prevention or attenuation of the disease as pre-exposure prophylaxis in close contacts of confirmed cases. (AU)

[Vaccines against monkeypox]. / Vacunas frente a la viruela del mono (monkeypox).

The monkeypox virus is a virus that has 90% genomic homology with the human (smallpox), but it is naturally transmitted between different wild animal reservoirs and is considered a zoonosis. Throughout the 20th century, different vaccines based on the vaccinia poxvirus were developed and used for vaccination against smallpox. After the eradication of smallpox, these vaccines were no longer used. Current vaccines against monkeypox virus are classified by the WHO as replicative (ACAM2000), minimally replicative (LC16m8) and non-replicative (MVA-BN), the latter being the one currently used. The 2022 extra-African monkeypox virus epidemic has highlighted the lack of vaccines with proven efficacy and low reactogenicity. It is considered that the use of this vaccine in the current outbreak may play a role in the prevention or attenuation of the disease as pre-exposure prophylaxis in close contacts of confirmed cases.

EDP-938, un nuevo antiviral con actividad inhibidora frente a la nucleoproteína del virus respiratorio sincitial / EDP-938, a new antiviral with inhibitory activity against the nucleoprotein of the respiratory syncytial virus

La ausencia de una vacuna eficaz frente al virus respiratorio sincitial (VRS) ha determinado el desarrollo de diversos fármacos con capacidad para inhibir o bloquear su actividad replicadora. Los de primera generación, denominados inhibidores de la fusión, se fijan a la proteína F de la superficie viral y evitan la unión y entrada del virus en la célula. Sin embargo su baja eficacia ha determinado el inicio de los estudios con los compuestos de segunda generación capaces de unirse o bloquear la nucleoproteína (N); la mayoría de estos compuestos son análogos de las 1,4-benzodiacepinas. El EDP-938 ha mostrado una elevada eficacia frente al VRS. Los primeros ensayos realizados en humanos han mostrado que este antiviral se absorbe de forma rápida tras su administración oral y presenta una vida media de entre 11-18 horas La administración durante siete días de múltiples dosis orales de hasta 600 mg/día o 300 mg/2 veces al día, no presentaban apenas efectos adversos significativos y disminuía significativamente la carga viral a nivel del tracto respiratorio inferior. (AU)

The absence of an effective vaccine against respiratory syncytial virus (RSV) has led to the development of various drugs with the ability to inhibit or block its replicative activity. The first generation, called fusion inhibitors, bind to the protein on the viral surface and prevent the virus from binding and entering the cell. However, its low efficacy has determined the start of studies with second-generation compounds capable of binding or blocking the nucleoprotein (N); most of these compounds are analogs of 1,4-benzodiazepines. EDP-938 has shown high efficacy against RSV. The first trials in humans have shown that this antiviral is rapidly absorbed after oral administration and has a half-life of between 11-18 hours Administration for seven days of multiple oral doses of up to 600 mg/day or 300 mg/day/twice a day, there were hardly any significant adverse effects and the viral load in the lower respiratory tract decreased significantly. (AU)

[The new generation of messenger RNA (mRNA) vaccines against influenza]. / La nueva generación de vacunas de ARN mensajero (ARNm) frente a la gripe.

Today there are multiple types of flu vaccines. The emergence of nucleic acid technology used in vaccines against SARS-CoV-2 suggests its future application against this infection. Against influenza, two types of vaccines have been developed based on messenger RNA (mRNA): conventional or non-replicative and self-amplifying or replicative (auRNA), both included in lipid nanoparticles. Animal studies carried out with the former have shown their strong capacity to induce Th-1 antibodies and cellular immunity against influenza haemagglutinin (HA) with few side effects. Human trials have shown 87% seroconversion and 100% seroprotection. The auRNA vaccines have obtained similar results in animals but at a concentration 64 times lower than the conventional one. Vaccines based on mRNA platforms meet the WHO requirements for next generation influenza vaccines.

The new generation of messenger RNA (mRNA) vaccines against influenza.

Today there are multiple types of flu vaccines. The emergence of nucleic acid technology used in vaccines against SARS-CoV-2 suggests its future application against this infection. Against influenza, two types of vaccines have been developed based on messenger RNA (mRNA): conventional or non-replicative and self-amplifying or replicative (auRNA), both included in lipid nanoparticles. Animal studies carried out with the former have shown their strong capacity to induce Th-1 antibodies and cellular immunity against influenza haemagglutinin (HA) with few side effects. Human trials have shown 87% seroconversion and 100% seroprotection. The auRNA vaccines have obtained similar results in animals but at a concentration 64 times lower than the conventional one. Vaccines based on mRNA platforms meet the WHO requirements for next generation influenza vaccines.

Los linajes Victoria y Yamagata de los virus gripales B, desconocidos y poco valorados / The Victoria and Yamagata Lineages of Influenza B Viruses, unknown and undervalued

El virus gripal B pertenece a la familia Orthomyxoviriridae y al género Influenzavirus B. Presenta un genoma de tipoARN negativo formado por unos 14.648 nucleótidos divididosen ocho segmentos distintos que codifican unas 11 proteínas.Antes de 1980 todos los virus de la gripe B pertenecían a unúnico linaje genético; pero en este año emergieron dos linajesantigénica y genéticamente distintos que se denominaron B/Victoria/2/1987 y B/Yamagata/16/1988. Se han podido demostrar procesos de intercambio genético intralinajes y entrelinajes; de ellos los mas frecuentes son aquellos en los que el linajeVictoria adquiere genes del linaje Yamagata. Se ha propuestoque las diferencias en las dinámicas evolutivas de los dos linajesse deban a las diferentes preferencias de unión de la hemaglutinina gripal al receptor celular. El linaje Victoria ha mostradocapacidad para unirse a los receptores celulares con restos deácido siálico en las posiciones a-2,3 y a-2,6; mientras que ellinaje Yamagata lo hace exclusivamente en las posiciones humanas a-2,6 del tracto respiratorio. La escasa circulación enlos últimos meses podría haber contribuido a la eliminación(“extinción”) temporal del linaje Yamagata. Desde 2017 la casitotalidad de las cepas de este linaje pertenecen al clado 3A,cuando con anterioridad se detectaban clados múltiples circulando. Aunque este clado 3A es diverso a nivel genético y haadquirido mutaciones sustitutivas en el gen de la hemaglutinina, éstas no han determinado cambios antigénicos significativos que hayan obligado a sustituir su componente antigénico(B/Pukhet/3073/2013) en la vacuna gripal desde 2015. (AU)

The influenza virus B belongs to the family Orthomyxoviriridae and to the genus Influenzavirus B. It has a negativeRNA-type genome made up of about 14,648 nucleotides divided into eight different segments that encode about 11 proteins.Before 1980 all influenza B viruses belonged to a single geneticlineage; but in this year two antigenically and genetically distinct lineages emerged which were named B/Victoria/2/1987and B/Yamagata/16/1988. Intralineage and interlineage genetic exchange processes have been demonstrated; The most frequent of them are those in which the Victoria lineage acquiresgenes from the Yamagata lineage. It has been proposed thatthe differences in the evolutionary dynamics of the two lineages are due to the different binding preferences of influenzahemagglutinin to the cellular receptor. The Victoria lineage hasshown the ability to bind to cell receptors with sialic acid residues at the α-2,3 and α-2,6 positions; whereas the Yamagatalineage does so exclusively in the human α-2,6 positions of therespiratory tract. Low circulation in recent months may havecontributed to the temporary elimination (“extinction”) of theYamagata lineage. Since 2017, almost all of the strains of thislineage belong to clade 3A, when previously multiple circulating clades were detected. Although this clade 3A is diverse atthe genetic level and has acquired surrogate mutations in thehemagglutinin gene, these have not determined significantantigenic changes that have made it necessary to replace itsantigenic component (B/Pukhet/3073/2013) in the influenzavaccine since 2015. (AU)

Nirmatrelvir más ritonavir (Paxlovid) una potente combinación inhibidora de la proteasa 3CLpro del SARS-CoV-2 / Nirmatrelvir plus ritonavir (Paxlovid) a potent SARS-CoV-2 3CLpro protease inhibitor combination

Todos los coronavirus, incluido el SARS-CoV-2, codificandos proteasas necesarias para el procesado de las poliproteínaspp1a y pp1ab. La proteasa principal 3CL (quimiotripsina-like) dalugar a la formación de las proteínas nsp11/16. La proteasa 3CLse ha constituido como una de las posibles dianas terapéuticaspara el desarrollo de fármacos antivirales frente al SARS-CoV-2debido a su secuencia y estructura altamente conservada entretodos los coronavirus. Durante la pandemia del SARS-CoV-1 seidentificó un derivado hidroximetilcetona (PF-00835231) conuna intensa actividad inhibidora frente a la proteasa 3CL. Lasmodificaciones químicas posteriores dieron lugar al derivadoPF-07321332 (nirmatrelvir) que ha mostrado una elevada eficacia antiviral frente al SARS-CoV-2. Los datos de la compañíaindican que es capaz de reducir un 89% el riesgo de hospitalización y fallecimiento de los pacientes infectados con apenasefectos adversos. Su eficacia mejora si se administra por vía oralen las primeras 24-48 horas y la duración del tratamiento se haestablecido entre 3-5 días. La forma comercial lleva asociadael antiviral ritonavir que ha mostrado enlentecer el metabolismo de nirmatrelvir, alargando su vida media. Este antiviral seríaeficaz frente a las actuales y futuras variantes virales, ya quela 3CL no se modifica en ellas. La FDA aprobó este antiviral ennoviembre de 2021 y la EMA está en fase de evaluación final. (AU)

All coronavirus, including SARS-CoV-2, encode two proteases needed for the processing of PP1A and PP1AB polyproteins. The main protease 3CL (chemotripsine-like) gives rise tothe formation of NSP11/16 proteins. The 3CL protease has beenconstituted as one of the possible therapeutic targets for thedevelopment of antiviral drugs against SARS-COV-2 due to itshighly conserved sequence and structure among all coronaviruses. During the SARS-COV-1 pandemic, a hydroxymethyl ketone derivative (PF-00835231) was identified with an intenseinhibitory activity against the 3CL protease. Subsequent chemical modifications gave rise to derivative PF-07321332 (nirmatrelvir) which has shown a high antiviral efficacy againstSARS-COV-2. The company’s data indicate that it is capable ofreducing 89% the risk of hospitalization and death of patientsinfected with hardly adverse effects. Its effectiveness improvesif it is administered orally in the first 24-48 hours and the duration of treatment has been established between 3-5 days. Thecommercial form has been associated with the antiviral ritonavir that has shown the metabolism of nirmatrelvir, lengtheningits average life. This antiviral would be effective against currentand future viral variants, since 3CL is not modified in them. TheFDA approved this antiviral in November 2021 and EMA is inthe final evaluation phase. (AU)

Surveillance for Enteroviruses Associated with Hand, Foot, and Mouth Disease, and Other Mucocutaneous Symptoms in Spain, 2006-2020.

Hand, foot, and mouth disease (HFMD) is a mild illness caused by enteroviruses (EV), although in some Asian countries, large outbreaks have been reported in the last 25 years, with a considerable incidence of neurological complications. This study describes epidemiological and clinical characteristics of EV infections involved in HFMD and other mucocutaneous symptoms from 2006 to 2020 in Spain. EV-positive samples from 368 patients were included. EV species A were identified in 85.1% of those typed EV. Coxsackievirus (CV) A6 was the prevalent serotype (60.9%), followed by EV-A71 (9.9%) and CVA16 (7.7%). Infections affected children (1-6 years old) mainly, and show seasonality with peaks in spring-summer and autumn. Clinical data indicated few cases of atypical HFMD as well as those with neurological complications (associated with the 2016 EV-A71 outbreak). Phylogenetic analysis of CVA6 VP1 sequences showed different sub-clusters circulating from 2010 to present. In conclusion, HFMD or exanthemas case reporting has increased in Spain in recent years, probably associated with an increase in circulation of CVA6, although they did not seem to show greater severity. However, EV surveillance in mucocutaneous manifestations should be improved to identify the emergence of new types or variants causing outbreaks and more severe pathologies.

Utilidad de la sangre seca del talón (tarjeta de Guthrie) en el diagnóstico de infección congénita por enterovirus / Use of dried blood from the heel (Guthrie card) in the diagnosis of congenital enterovirus infection

No disponible

La vacunación de la gripe en el tiempo del SARS-CoV-2 / Influenza vaccination in the time of SARS-CoV-2

No disponible