Vacunas contra el virus chikungunya: avances y perspectivas

El virus chikungunya (CHIKV) es un alfavirus cuya infección provoca una enfermedad caracterizada principalmente por fiebre y dolores articulares/musculares. Entre 25-50% de las infecciones se presentan con enfermedad crónica que puede durar de meses a años. El primer brote de CHIKV en Paraguay corresponde al año 2015, siendo el último en el año 2022/2023. Diversos candidatos vacunales contra CHIKV se encuentran en diferentes etapas de desarrollo, e incluso recientemente (noviembre/2023) fue aprobada la primera vacuna contra CHIKV llamada VLA1553 (Ixchiq). Adicionalmente, al menos 30 candidatos vacunales se encuentran en ensayos preclínicos/clínicos. Con la aprobación de la primera vacuna contra CHIKV y la posibilidad de otras que lleguen al mercado prontamente, debido al estado avanzado de otros candidatos vacunales, se abrirá un nuevo escenario en esta enfermedad. Se espera que la introducción de vacunas efectivas genere un avance importante para la prevención de esta enfermedad, disminuyendo los casos agudos y los efectos crónicos de la infección por el virus. En este trabajo de revisión se analiza el avance de las vacunas contra CHIKV, además de examinar los desafíos de vigilancia epidemiológica que plantean la introducción de estas vacunas.

Chikungunya virus (CHIKV) is an alphavirus that causes an illness characterized mainly by fever and joint/muscle pain. Between 25-50% of infections present with chronic diseases that can last from months to years. The first outbreak of CHIKV in Paraguay occurred in 2015, with the last outbreak occurring in 2022/2023. Several vaccine candidates against CHIKV are in different stages of development, and even recently (November/2023), the first vaccine against CHIKV, called VLA1553 (Ixchiq), was approved. In addition, at least 30 vaccine candidates are available for preclinical and clinical trials. With the approval of the first vaccine against CHIKV and the possibility of others coming to the market soon, due to the advanced status of other vaccine candidates, a new scenario will open for this disease. The introduction of effective vaccines is expected to generate an important advance in the prevention of this disease, reducing acute cases and the chronic effects of viral infection. This review analyzes the progress of CHIKV vaccines and examines the epidemiological surveillance challenges posed by the introduction of these vaccines.

Estabilidade dimensional de moldes obtidos com alginato de armazenamento tardio / Dimensional stability of molds obtained with late storage alginate

Resumo Introdução Recentemente, vêm surgindo no mercado alguns alginatos de armazenamento prolongado. Não há, no entanto, um consenso na literatura a respeito da estabilidade dimensional destes materiais durante este armazenamento Objetivo Avaliar, por meio de método prático experimental, a estabilidade dimensional de um alginato de armazenamento tardio. Material e método O material de moldagem utilizado foi o alginato Hydrogum 5 (Zhermack). Uma matriz metálica cilíndrica foi utilizada para a realização das moldagens, com 38 mm de diâmetro externo, 30 mm de diâmetro interno e cuja superfície superior apresenta três linhas paralelas entre si com 25 mm de comprimento e 20, 50 e 75 µm de largura. Após o tempo de geleificação do material de moldagem, 16 moldes foram colocados em um umidificador e essas amostras foram fotografadas utilizando-se uma câmera digital (Canon EOS Rebel 3Ti, Canon) associada a um software para análise das imagens obtidas (ImageJ 1.52a, U.S. National Institutes of Health; DI). A calibragem da régua foi 10 cm e, posteriormente, três linhas foram medidas três vezes, para se obter uma média dos comprimentos das linhas. As amostras foram fotografadas nos seguintes intervalos: imediatamente, 24, 48, 72, 96 e 120 horas. Resultado Os dados mostraram diferenças estatisticamente significantes para o fator tempo quando comparada a leitura imediata com os demais períodos de tempo de leitura (p<0,001) e quando comparada a leitura após 24 h de armazenagem com os demais períodos de tempo (p<0,001). Não houve diferença estatística (p>0,05) quando os tempos de armazenamento de 48 h, 72 h, 96 h e 120 h foram comparados entre si. Todos os valores encontravam-se dentro dos valores preconizados pela ISO 21563:2013. Conclusão Os moldes dos alginatos testados podem ser armazenados por até cinco dias em 100% de umidade relativa.

Abstract Introduction Recently, some extended-pour alginate impression materials have been placed in the market. However, there is no consensus in the literature regarding the dimensional stability of these materials during these storage. Objective To evaluate, through the experimental model, the durability and velocity with respect to dimensional alteration, analyzing the material and detecting distortions. Material and method The material for molding in this test was alginate (Hydrogum 5, Zhermack). A cylindrical metallic matrix was used to make the moldings with: 38 mm of external diameter, 30 mm of internal diameter and superior of the upper series of the card 3d transport lines with each 25 mm in length and 20, 50 and 75μm in width. After the time of jellification / polymerization of the molding material, 16 molds were inserted in a doser and were photographed with a digital camera (Canon EOS Rebel 3Ti, Canon) associated with a software for analysis of sacred images (ImageJ 1.52a, US National Institutes of Health, DI). The calibration of the ruler was performed in 10 cm and then in 3 lines were means 3 (three) times to obtain a mean of the lengths of the lines. The photographs were taken at the following intervals: immediately, 24, 48, 72, 96 and 120 hours after being cast. Result The data were found when compared with the other parts of the reading time (p <0.001) and when compared to the execution after 24 hours of locomotion with the other parts of the time (p <0.001). The rest time of 48 hours, 72 hours, 96 hours and 120 hours were compared to each other. Conclusion The molds of the tested alginates can be stored for 5 days in 100% relative sauce.

Extractos vegetales de tres especies del género Baccharis inducen la proliferación de células mononucleares humanas / Plant extracts of three species of the genus Baccharis induce human mononuclear cells proliferation

Las plantas de uso en medicina tradicional constituyen una fuente importante de compuestos con actividad inmunomoduladora; entre ellas las especies del género Baccharis, conocidas popularmente como "Jaguareteka´a" en nuestro país, son ampliamente empleadas. En este estudio se evaluó la actividad inmunomoduladora de extractos metanólicos de tres especies del género Baccharis (B. trimera, B. notosergilay B. punctulata) sobre la proliferación de células mononucleares humanas de sangre periférica. Los extractos de las tres especies estudiadas estimularon la proliferación de las células mononucleares. Específicamente, el extracto de B. notosergila estimuló la proliferación celular a todas las concentraciones probadas (5, 10, 25 y 50 µg/mL), mientras que los extractos de B. trimera y B. punctulata mostraron este efecto a 5 y 10 µg/mL. Además, por presentar mayor inducción de la proliferación, se realizó un fraccionamiento con diferentes solventes del extracto metanólico de B. notosergila y B. punctulata. La fracción de acetato de etilo de ambos extractos vegetales aumentó la proliferación celular, sugiriendo que compuestos de polaridad media son los responsables de esta actividad. Estos resultados demuestran que los extractos de B. trimera, B. notosergila y B. punctulata poseen actividad inmunomoduladora sobre células mononucleares humanas y servirán de base a otros estudios para determinar el o los componentes activos de los extractos sobre el sistema inmune(AU)

Plants used in traditional medicine are an important source of compounds with immunomodulatory activity. Species of the genus Baccharis, popularly known as "Jaguareteka'a" in our country, are used in folk medicine for the treatment of liver, gastrointestinal, inflammatory and infectious diseases. In this study, we evaluated the immunomodulatory activity of methanolic extracts of three species of the genus Baccharis (B. trimera, B. notosergila and B. punctulata) on the proliferation of human peripheral blood mononuclear cells. Extracts of the three species studied stimulated the proliferation of mononuclear cells. The extract of B. notosergila stimulated cell proliferation at all concentrations tested, while extracts of B. trimera and B. punctulata stimulated at 5 and 10 µg/mL. In addition, we carried out a separation with different solvents of the methanolic extract of B. notosergila and B. punctulata. The ethyl acetate fraction of both plant extracts induced the proliferation of immune cells. These results show that the extracts of B. trimera, B. notosergila and B. punctulata had immunomodulatory activity on human mononuclear cells. Future work will be required to identify the components responsible for the activity on the immune system(AU)

Presente y futuro de los anticuerpos recombinantes terapéuticos / Present and future of therapeutic recombinant antibodies

Los anticuerpos constituyen un componente fundamental del sistema inmune, permitiendo el reconocimiento con alta especificidad y posterior destrucción de moléculas extrañas. Los anticuerpos monoclonales, producidos por la tecnología del hibridoma, presentan desventajas para su uso en terapia humana debido a su origen en una especie diferente. La ingeniería genética posibilitó la utilización de los anticuerpos monoclonales para terapias humanas, generando los anticuerpos recombinantes terapéuticos. Así, los anticuerpos recombinantes se han transformado en un importante grupo de fármacos; con decenas de ellos aprobados para terapia humana y cientos en desarrollo. Se utilizan con éxito como tratamiento para un amplio rango de patologías, tales como cáncer, autoinmunidad e infecciones, siendo desde hace años el biofármaco con mayores ventas. Inicialmente todos los anticuerpos recombinantes terapéuticos presentaban la estructura convencional de los anticuerpos. Sin embargo, más recientemente, se han generado nuevos diseños que no poseen las características estructurales naturales, como los anticuerpos de simple cadena y bi-específicos. Debido al desarrollo y éxito de la tecnología de anticuerpos recombinantes, se espera un aumento constante en el número de anticuerpos terapéuticos contra nuevos blancos, además de la generación de nuevas estructuras, usos y estrategias terapéuticas. En esta revisión, nos centraremos en las características estructurales y los nuevos formatos de anticuerpos, así como su aplicación clínica en el tratamiento de diversas patologías. Además analizaremos los nuevos formatos de anticuerpos que se encuentran en el mercado y la aparición de los anticuerpos biosimilares.

Antibodies are a key component of the immune system, acting in the highly specific recognition and subsequent destruction of foreign molecules. Monoclonal antibodies produced by hybridoma technology have disadvantages for use in human therapy becauseof its origin in a different species. Genetic engineering enabled the use of monoclonalantibodies for human therapies, generating recombinant therapeutic antibodies. Thus, the recombinant antibodies have become an important group of drugs; dozens of them are approved for human therapy and there are hundreds in development. They are successfully used as a treatment for a wide range of pathologies, such as cancer, autoimmunity and infections, being the biopharmaceutical with higher sales. Initially therapeutic recombinant antibodies showed the conventional structure of the antibodies. However, more recently, new designs that do not have natural structural features havebeen generated such as single chain formats and bi-specific antibodies. Due to development and success of recombinant antibody technology, a steady increase in the number of newtherapeutic drugs against new targets is expected in addition to the generation of new structures, uses and therapeutic strategies. In this review, we will focus on their structural features and clinical application in the treatment of various pathologies. We will also discuss new formats of antibodies and the emergence of biosimilar antibodies.