Eficacia y seguridad de vacunas contra SARS-CoV-2 en pacientes con enfermedades reumatológicas autoinmunes

Los pacientes con enfermedades reumatológicas autoinmunes tienen mayor riesgo de infección por SARS-CoV-2 por factores propios de la enfermedad, así como los derivados por el tratamiento, con el desarrollo de vacunas se ha priorizado la inmunización en este grupo de pacientes, no obstante, la eficacia y seguridad de vacunas contra SARS-CoV-2 no se ha estudiado en esta población por su exclusión en los ensayos clínicos de fase II-III. Objetivo. analizar la eficacia y seguridad de vacunas contra SARS-CoV-2 en pacientes con enfermedades reumatológicas autoinmunes. Metodología. Se realizó una revisión sistemática, usando la declaración PRISMA, como criterios de búsqueda fueron considerados publicaciones portugués, inglés y español, relacionada con la eficacia y seguridad de vacunas contra SARS-CoV-2 durante los últimos 6 años. La búsqueda de artículos se desarrolló en las bases de datos como PubMed, Scopus y ScienceDirect publicados en idiomas inglés, portugués y español publicados durante los últimos 6 años hasta la actualidad. Resultados. Se encontraron 79 artículos, 27 en PubMed, en Google Scholar 52; la cantidad se redujo a 60, eliminando 19 por duplicidad, 27 por resumen de artículo, luego de un análisis exhaustivo del contenido de la información para así obtener un total de 8 artículos para el análisis del estudio. Conclusión. La eficacia de vacunas contra SARS-CoV-2 en pacientes con enfermedades reumatológicas se encuentra reducida, atribuida al uso de glucocorticoides y de terapias inmunosupresoras en las que se destaca rituximab, micofenolato de mofetilo y metotrexato, mientras que la seguridad basada en los efectos adversos es similar a los encontrados en la población general.

Patients with autoimmune rheumatologic diseases have a higher risk of infection by SARS-CoV-2 due to factors inherent to the disease, as well as those derived from treatment. With the development of vaccines, immunization has been prioritized in this group of patients; however, the efficacy and safety of vaccines against SARS-CoV-2 has not been studied in this population due to their exclusion in phase II-III clinical trials. Objective. to analyze the efficacy and safety of vaccines against SARS-CoV-2 in patients with autoimmune rheumatologic diseases. Methodology. A systematic review was performed, using the PRISMA statement, as search criteria were considered Portuguese, English and Spanish publications, related to the efficacy and safety of vaccines against SARS-CoV-2 during the last 6 years. The search for articles was developed in databases such as PubMed, Scopus and ScienceDirect published in English, Portuguese and Spanish published during the last 6 years to date. Results. A total of 79 articles were found, 27 in PubMed, 52 in Google Scholar; the number was reduced to 60, eliminating 19 for duplicity, 27 for article ABSTRACT, after an exhaustive analysis of the content of the information to obtain a total of 8 articles for the analysis of the study. Conclusion. The efficacy of vaccines against SARS-CoV-2 in patients with rheumatologic diseases is reduced, attributed to the use of glucocorticoids and immunosuppressive therapies in which rituximab, mycophenolate mofetil and methotrexate stand out, while safety based on adverse effects is similar to those found in the general population.

Pacientes com doenças reumatológicas autoimunes têm maior risco de infecção pelo SARS-CoV-2 devido a fatores inerentes à doença, bem como àqueles derivados do tratamento. Com o desenvolvimento de vacinas, a imunização tem sido priorizada nesse grupo de pacientes; no entanto, a eficácia e a segurança das vacinas contra o SARS-CoV-2 não foram estudadas nessa população devido à sua exclusão dos ensaios clínicos de fase II-III. Objetivo. Analisar a eficácia e a segurança das vacinas contra o SARS-CoV-2 em pacientes com doenças reumatológicas autoimunes. Metodologia. Foi realizada uma revisão sistemática utilizando a declaração PRISMA, tendo como critério de busca publicações em português, inglês e espanhol relacionadas à eficácia e à segurança de vacinas contra o SARS-CoV-2 nos últimos 6 anos. A busca de artigos foi desenvolvida em bancos de dados como PubMed, Scopus e ScienceDirect, publicados em inglês, português e espanhol, publicados nos últimos 6 anos até o presente. Resultados. Foram encontrados 79 artigos, 27 no PubMed, 52 no Google Scholar; o número foi reduzido para 60, eliminando 19 por duplicidade, 27 por resumo do artigo, após uma análise exaustiva do conteúdo das informações para obter um total de 8 artigos para a análise do estudo. Conclusões. A eficácia das vacinas SARS-CoV-2 em pacientes com doenças reumatológicas é reduzida, atribuída ao uso de glicocorticoides e terapias imunossupressoras, incluindo rituximabe, micofenolato mofetil e metotrexato, enquanto a segurança baseada em efeitos adversos é semelhante à encontrada na população em geral.

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.

Anticuerpos neutralizantes, nuevas pruebas de laboratorio contra el SARS-CoV-2 / Neutralizing antibodies, new laboratory tests against SARS-CoV-2

RESUMEN Introducción: En la presente revisión conoceremos los detalles de esta nueva prueba de laboratorio, utilizada para cuantificar los anticuerpos neutralizantes contra el SARS-CoV-2. Esta prueba diagnóstica comienza a tener un mayor protagonismo, a razón del proceso de infección y vacunación en el mundo, para comprender los misterios del correlato de protección inmunológica. Contenido: Los anticuerpos neutralizantes pueden bloquear la capacidad del virus, para unirse al receptor ACE2 en las células humanas y estos anticuerpos permiten eliminar el efecto de microorganismos invasores. Su actividad se genera por las proteínas situadas en la superficie de los virus, a las que se unen para «bloquear¼ la infección. Los anticuerpos neutralizantes se definen in vitro por su capacidad para bloquear la entrada, fusión o salida del coronavirus, es decir son anticuerpos funcionales. En la actualidad existen diferentes pruebas de laboratorio (pruebas de inmunoensayo de alto rendimiento), que pueden detectar anticuerpos inmunoglobulinas G anti proteína S del SARS-CoV-2 y que se correlacionan con las pruebas de laboratorio idóneas para la determinación de estos anticuerpos. Es crucial que estas pruebas de inmunoensayo de alto rendimiento, sean validadas en su fabricación comparándolas con los métodos gold standard para determinar la presencia de anticuerpos neutralizantes. Perspectiva: Se pretende ampliar el conocimiento de esta nueva prueba, que en un futuro permitirán definir los valores de correlato inmunológico generados por las vacunas o por una infección previa.

ABSTRACT Introduction: In this review we will know the details of this new laboratory test, used to quantify neutralizing antibodies against SARS-CoV-2. This diagnostic test begins to have a greater role, due to the process of infection and vaccination in the world, to understand the mysteries of the correlate of immune protection. Content: Neutralizing antibodies can block the ability of the virus to bind to the ACE2 receptor in human cells and these antibodies allow to eliminate the effect of invading microorganisms. Their activity is generated by proteins on the surface of viruses, which they bind to "block" infection. Neutralizing antibodies are defined in vitro by their ability to block the entry, fusion or exit of the coronavirus, that is, they are functional antibodies. Currently there are different laboratory tests (high-throughput immunoassay tests), which can detect immunoglobulin G anti-protein S antibodies to SARS-CoV-2 and which correlate with the gold standard laboratory tests for the determination of these antibodies. It is crucial that these high-throughput immunoassay tests are manufacturing validated against gold standard methods to determine the presence of neutralizing antibodies. Perspective: This review aims to expand the knowledge of this new test, which in the future will allow defining the immunological correlate values generated by vaccines or by a previous infection.

Immunogenicity after CoronaVac vaccination

SUMMARY OBJECTIVE: This study aimed to investigate the seropositivity of CoronaVac-SinoVac vaccination in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) risk factors and comorbidities. METHODS: Immunoglobulin (IgG) antibody responses were examined on the 21st day after the second dose of CoronaVac-SinoVac 6 μg vaccine on the 28th day. SARS-CoV-2 IgG antibody levels were measured by using the enzyme-linked immunosorbent assay method in vaccinated health care workers (n=134) (Group I), vaccinated polymerase chain reaction (PCR) (+) who had coronavirus-19 (COVID-19) disease (n=21) (Group II), and unvaccinated PCR (+) (n=28) (Group III) participants. Subgroups were formed in Group I according to the presence of COVID-19 risk factors and comorbidities (diabetes mellitus, cardiovascular disease, and asthma/allergy) and demographic data. RESULTS: Seropositivity rates were 95.5, 100, and 89.3% for Groups I, II, and III, respectively. IgG antibody levels were found significantly higher in the group between the ages of 20-30 in group I compared to those aged 31-50 and over 50 (both p<0.01). It was found significantly higher in normal-weight individuals than in the overweight and obese group (both p<0.01). IgG antibody levels were found significantly lower in people with cardiovascular disease and diabetes mellitus compared with those who did not (p<0.05 and p<0.001, respectively). There was a negative correlation between IgG antibody response values and body mass index and age in Group I (r= −0.336, p<0.001 and r= −0.307, p<0.001, respectively). CONCLUSION: IgG antibody values decrease with age and with increasing body mass index. The presence of comorbidities (i.e., diabetes mellitus and cardiovascular disease) decreased COVID-19 IgG antibody values.

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.

SARS-CoV-2 vaccines-induced thrombotic thrombocytopenia: should we consider immuno-hypersensitivity?

ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic is significantly causing unprecedented clinical, socioeconomic, and public health challenges globally. The successful global administration of effective, safe and sustainable vaccine(s) is widely believed to be crucial in mitigating as well as preventing COVID-19. However, the rising cases of severe adverse events following immunization (AEFI) with COVID-19 vaccines including thrombosis, thrombocytopenia, and in some instances, death have created serious global concerns and could enormously contribute to vaccine hesitancy. Although the complete underlying pathophysiology and immunopathology of the COVID-19 vaccines related to AEFI, including thrombosis and/or anaphylaxis, are yet to be determined, exploring possible immuno-hypersensitivity could be crucial in the mechanisms associated with these reactions, thereby mitigating their occurrences as well as restoring confidence in vaccine administration for a COVID-19 free world.

Diseño y evaluación de una proteína multiepitópica como candidata para vacuna contra la enfermedad de carrión / Design and evaluation of a multiepitopic protein as a candidate for a carrion disease vaccine

RESUMEN Objetivos. Diseñar y evaluar una proteína multiepítope como candidato a vacuna contra la enfermedad de Carrión. Materiales y métodos. Mediante herramientas bioinformáticas se seleccionó epítopes de proteínas de membrana externa y se diseñó una proteína multiepítope. El gen de la proteína multiepítope fue subclonado en el plásmido de expresión pET28b y transformado en E. coli BL21 pLys. La proteína multiepítope fue expresada usando isopropil-β-D-1-tiogalactopiranósido y purificada usando resina. Esta proteína purificada fue utilizada para inmunizar ratones BALB/c y se obtuvo anticuerpos policlonales. Se realizaron ensayos de invasión in vitro usando una cepa de Bartonella bacilliformis (B. bacilliformis) a eritrocitos humanos. Resultados. La proteína multiepítope M1 presenta epítopes conservados entre aislamientos de B. bacilliformis, no tóxicos, no homólogos a proteínas humanas y superficiales. Los ratones inmunizados presentaron niveles de anticuerpos IgG capaces de reducir in vitro la tasa de invasión de B. bacilliformis a eritrocitos humanos. Conclusiones. La proteína multiepítope M1 podría servir como candidato a vacuna contra la enfermedad de Carrión; sin embargo, se requiere de más estudios para caracterizar el uso de este antígeno como vacuna.

ABSTRACT Objectives. To design and assess a multiepitopic protein as a candidate for a vaccine against Carrion disease. Materials and Methods. Using bioinformatics tools, epitopes of external membrane proteins were selected and a multiepitopic protein was designed. The multiepitopic protein gene was subcloned into the expression plasmid pET28b and transformed into E. coli BL21 pLys. The multiepitopic protein was expressed using isopropyl-β-D-1-thiogalactopyranoside and purified using resin. This purified protein was used to immunize BALB/c mice obtaining polyclonal antibodies. In vitro invasion assays were conducted using a strain of Bartonella bacilliformis (B. bacilliformis) in human red blood cells. Results. The multiepitopic protein M1 presents preserved epitopes between isolates of B. bacilliformis with are non-toxic, and not homologous to human and surface proteins. Immunized mice presented IgG antibody levels capable of reducing in vitro the rate of invasion of B. bacilliformis into human red blood cells. Conclusions. Multiepitopic protein M1 may serve as a candidate for a Carrion disease vaccine; however, more studies are needed to characterize the use of this antigen as a vaccine.

Revisión de estudios pre-clínicos de candidatos a vacuna contra la malaria causada por Plasmodium falciparum / Review of preclinical studies of candidates for malaria vaccine caused by Plasmodium falciparum / Revisão de estudos pré-clínicos de candidatos á vacina contra a malária causados por Plasmodium falciparum

Introducción. La malaria es una enfermedad que causa aproximadamente 400.000 muertes al año, especialmente en niños menores de 5 años; la búsqueda de una vacuna eficaz y segura sigue siendo un reto para los investigadores, sin embargo, antes de iniciar los estudios de fase clínica, los ensayos preclínicos en modelo animal deben brindar resultados de seguridad e inmunogenicidad que lleven a respuestas eficaces de protección. Objetivo. Revisar las principales características de la respuesta inmunológica y eficacia en estudios pre-clínicos de candidatos a vacuna contra la malaria por Plasmodium falciparum. Métodos. Revisión descriptiva de los principales estudios preclínicos de candidatos a vacuna contra la malaria, basados en subunidades, parásitos atenuados y vacunas multi-estadio, multi-epitope, que se han realizado para evaluar inmunogenicidad y eficacia en modelo animal. Esta revisión se llevó a cabo a partir de la búsqueda de literatura en bases de datos electrónicas especializadas en investigación científica. Se encontraron 118 documentos, de los cuales se seleccionaron 91 y se excluyeron 17 por no cumplir con los criterios de inclusión, para un total de 74 referencias analizadas. Resultados. Muchos candidatos a vacuna contra la malaria causada por Plasmodium falciparum han reportado resultados prometedores contra cepas homologas, sin embargo, ante el reto con cepas heterólogas la eficacia disminuye, por otra parte, la respuesta inmune y protectiva duradera continúa siendo un objetivo clave, convirtiéndose en una prioridad. Conclusiones. Los estudios preclínicos en modelo animal son necesarios antes de avanzar a fases clínicas, la evaluación de inmunogenicidad y eficacia es un aspecto esencial para la evaluación de candidatos a vacuna.

Introduction. Malaria disease causes approximately 400,000 deaths by year, especially in children under 5 years, the search for an effective and safe vaccine, remains to be a challenge for researchers, however before starting the clinical phase studies, preclinical trials in animal models should provide safety and immunogenicity results that lead to effective protective responses. Objective. To review the main characteristics of the immune response and efficacy in pre-clinical studies of candidates for vaccine against malaria by Plasmodium falciparum. Methods. A descriptive review of the main preclinical studies of malaria vaccine candidates, based on subunits, attenuated parasites and multi-stage, multi-epitope vaccines, which have been carried out to evaluate immunogenicity and efficacy, is presented. This review was carried out based on the search of literature in electronic databases specialized in scientific research. 118 documents were found, of which 91 were selected and 17 were excluded because they did not meet the inclusion criteria, for a total of 74 references analyzed. Results. Many candidates for malaria vaccine caused by Plasmodium falciparum have reported promising results against homologous strains, however, given the challenge with heterologous strains, efficacy decreases, on the other hand, the lasting immune and protective response continues to be a key objective, becoming a priority. Conclusions. Preclinical studies in animal models are necessary before advancing to clinical phases, the evaluation of immunogenicity and efficacy is an essential aspect for the evaluation of vaccine candidates.

Introdução: A malária é uma doença que causa aproximadamente 400.000 óbitos por ano, principalmente em crianças menores de 5 anos, a procura por uma vacina eficaz e segura, continua sendo um desafio para os pesquisadores, porém, antes de iniciar os estudos de fase clínica, os testes pré-clínicos no modelo animal devem fornecer resultados de segurança e imunogenicidade que levam a respostas efetivas de proteção. Objetivo: Verificar as principais características da resposta imune e eficácia em estudos pré-clínicos de candidatos à vacina contra a malária por Plasmodium falciparum. Métodos: Revisão descritiva dos principais estudos pré-clínicos de candidatos à vacina contra a malária, com base em subunidades, parasitas atenuados e vacinas de vários estágios e multiepítopo, que foram realizadas para avaliar a imunogenicidade e eficácia em modelos animais. Esta revisão foi realizada com base na pesquisa de literatura em bases de dados eletrônicas especializadas em pesquisa científica. Foram encontrados 118 documentos, dos quais 91 foram selecionados e 17 foram excluídos por não atenderem aos critérios de inclusão, para um total de 74 referências analisadas. Resultados: Muitos candidatos à vacina contra a malária causada por Plasmodium falciparum relataram resultados promissores contra cepas homólogas, no entanto, diante do desafio com cepas heterólogas a eficácia diminui, por outro lado, a resposta imune e protetora duradoura continua sendo um objetivo fundamental, tornando-se uma prioridade. Conclusões: Estudos pré-clínicos em modelo animal são necessários antes de passar para as fases clínicas, a avaliação da imunogenicidade e eficácia é um aspecto essencial para a avaliação dos candidatos a vacina.

The effect of a booster dose of HPV tetravalent vaccine after 51 months: implications for extended vaccination schedules / El efecto de un refuerzo de la vacuna tetravalente de VPH después de 51 meses: implicaciones para un esquema de vacunación extendido

Abstract: Objective: To asses the non-inferiority between two different vaccination schedules one month after the administration of the third dose. Materials and methods: We evaluated the anti-HPV 16/18 antibody titers induced by quadrivalent HPV vaccine administered using two different schedules in girls 9 to 10-year-old girls: a traditional (0-2-6) and an alternative (0-6-50). Blood samples were collected at month 7, 21 and 51. Results: The antibody geometric mean titer ratios one month after the application of the third dose -month 51 for the alternative and month 7 for the traditional- were 1.55 for HPV16 (95%CI, 1.15-2.08) and 1.53 for HPV18 (95%CI, 1.12-2.09). The seropositive rate was above 99% in both groups. Conclusions: The application of an alternative 3-dose schedule in 9 to 10-year-old girls induces a non-inferior immune response compared to the standard one month after the last dose. Further research is needed to understand the minimal number of doses and their timing to provide the best coverage for HPV infection.

Resumen: Objetivo: Evaluar la no inferioridad entre dos diferentes esquemas de vacunación un mes después de la administración de la tercera dosis. Material y métodos: Se evaluaron los títulos de anticuerpos anti-VPH 16/18 inducidos por la vacuna contra VPH tetravalente administrada en niñas de 9 a 10 años utilizando dos esquemas diferentes: tradicional (0-2-6) y alternativo (0-6-50). Se recolectaron muestras en los meses 7, 21 y 51. Resultados: La media geométrica de títulos de anticuerpos un mes después de la aplicación de la tercera dosis -mes 51 para la alternativa y mes 7 para el tradicional- fueron 1.55 para HPV16 (95% IC 1.15-2.08) y 1.53 para HPV18 (95% IC 1.12-2.09). La tasa de seropositividad fue superior a 99% en ambos grupos. Conclusiones: la aplicación de un esquema alternativo de tres dosis (0-6-50 meses) en niñas parece inducir una respuesta inmune no inferior al esquema tradicional un mes después de la última dosis. Se necesitan más estudios para determinar las dosis mínimas e intervalos óptimos para obtener la mejor cobertura para la infección por VPH.

Immunogenicity of Different Genetic Type Rotavirus NSP4 in Mice / 中国生物工程杂志

NSP4, as the diarrhea-related protein of rotavirus, is becoming an attractive candidate for vaccine development. To compare the immunogenicity of NSP4 from different genetic groups, we constructed eukaryotic expression plasmids comprising the NSP4 genes from four different genetic types using the pCI vector. The recombinant vectors were designated as pCI-97B6, pCI-97S36, pCI-97S34 and pCI-97SZ8, respectively. Following the conformation of the transient expression of the constructs in 293 cells, the plasmids were respectively subjected to the 5 round i. m. inoculation of BALB/c mice. The specific antibodies against NSP4 as well as the IgG1/IgG2a subclasses of immunoglobulin in mice sera were examined with indirect ELJSA after each immunization. The results showed that the immunization of plasmids expression NSP4s could elicit not only humoral but also cellular immunity, but the humoral immune response is dominant. There is a difference of immunogenecity among the NSP4 of different genetic type. Further studies were needed to focus on the relationship between the immunogenicity and protection effect.