Hipertiroidismo por enfermedad de Graves posterior a vacuna contra SARS-CoV-2: reporte de 2 casos / Graves' disease hyperthyroidism following SARS-CoV-2 vaccination: a two cases report

Luego del inicio de las campañas de vacunación masiva contra la infección por COVID-19, se han publicado una serie de reportes que muestran la posible asociación entre la vacuna y alteraciones de la función tiroidea. Desde entonces, múltiples teorías han intentado explicar este hallazgo, en su mayoría de índole autoinmune. Dentro de estas destaca el síndrome autoinmune-autoinflamatorio secundario a adyuvantes (ASIA), que podría generar desórdenes tiroideos de novo o exacerbar los ya existentes. Presentamos dos casos de enfermedad de Graves Basedow posterior al uso de Coronavac. Ambas pacientes presentaron características similares a las descritas en la literatura y cumplen con los criterios de ASIA. No obstante, los beneficios de las vacunas superan los posibles riesgos asociados.

After the beginning of COVID-19 vaccination campaigns, a number of reports have shown the potential association between vaccines and thyroid disfunction. Since then several theories have tried to explain this finding, mostly autoinmmune. One of them is the autoimmune/inflammatory syndrome induced by adjuvants, that could trigger or exacerbate thyroid disease. We present two cases of Graves' disease post Coronavac vaccination. Both pacients share similar features than cases published previously and meet criteria for ASIA syndrome. Nevertheless, the benefts of vaccination largely outweigh any adverse events associated.

Advances in research of interchangeable immunization with live attenuated Japanese encephalitis vaccines and inactivated vaccines / 中华预防医学杂志

Japanese encephalitis (JE) virus is the leading cause of vaccine-preventable encephalitis in Asia and the Western Pacific, which mainly invades central nervous system. Vaccination is the most important strategy to prevent JE. Currently, both live attenuated Japanese encephalitis vaccines (JE-L) and inactivated vaccines (JE-I) are in use. Due to the supply of vaccines and the personal choice of recipients, there will be a demand for interchangeable immunization of these two vaccines. However, relevant research is limited. By reviewing domestic and foreign research evidence, this article summarizes the current situation of the interchangeable use of JE-L and JE-I, and makes recommendations when the interchangeable immunization is in urgent need, so as to provide reference for practical vaccination and policymaking in China.

Immunogenicity and safety of a severe acute respiratory syndrome coronavirus 2 inactivated vaccine in healthy adults: randomized, double-blind, and placebo-controlled phase 1 and phase 2 clinical trials / 中华医学杂志(英文版)

BACKGROUND@#The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults.@*METHODS@#Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose.@*RESULTS@#In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses.@*CONCLUSIONS@#Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).

Evaluación del riesgo biológico en la producción de vacunas inactivadas de uso animal / Biological risk assessment for the production of inactivated vaccines for animal use

La vacunación continúa siendo una de las vías más sostenibles y utilizadas en el control de enfermedades infectocontagiosas en medicina veterinaria, dado por su mayor factibilidad económica y por el problema que representa el residuo de antibióticos en productos animales de consumo humano. El surgimiento de vacunas de nuevas generaciones ha motivado la instrumentación de medidas de bioseguridad y la necesidad de realizar estudios de evaluaciones de los riesgos que acometemos en la obtención y producción de vacunas, existiendo puntos críticos importantes en el proceso de obtención de las mismas. El área de vacunas inactivadas que se encuentra ubicada en la Empresa Productora de Vacunas Virales y Bacterianas UP-7, perteneciente al grupo empresarial LABIOFAM de La Habana, Cuba, se encarga de la producción y control de la calidad de las vacunas y los medios diagnósticos. Las inspecciones previas realizadas a dicha área mostraron, en el personal involucrado, desconocimiento y baja percepción del riesgo biológico existente en los procesos productivos que allí se llevan a cabo, lo que sugirió la realización de la presente investigación. Se identificaron y caracterizaron los peligros y se realizó una evaluación del riesgo, utilizando una matriz de estimación del riesgo; mediante un método cualitativo de posibilidad de ocurrencia del peligro y se evaluó de bajo, moderado o alto. Se identificaron las vulnerabilidades presentes empleando para ello una lista de chequeo, detectándose, entre otras, aquellas relacionadas con el diseño del área, con el tratamiento de los desechos y la organización de la bioseguridad, lo que confirmó puntos críticos dentro del proceso productivo con riesgo alto y moderado(AU)

Vaccination continues being one of the most sustainable and used ways in the control of infectious and contagious diseases in veterinary medicine because of both its greater economic feasibility and thwarting animal products from having antibiotics residues, a big-time issue for human ingestion. The appearance of new generation vaccines has motivated the application of biosafety measures and the need to carry out studies of risk assessments that we undertake to obtaining and producing vaccines, being important critical points in the process of acquiring them. The inactivated vaccines' area is located in the UP-7 Viral and Bacterial Vaccine Production Company, belonging to LABIOFAM business group in Havana, Cuba; this area is responsible for vaccines, diagnostic means production and quality control. Previous checkups carried out showed that the personnel involved had lack of knowledge and low perception of the existing biological risk in the productive processes carried out there; leading to suggest the investigation. Hazards were identified and characterized and a risk assessment was carried out, using a qualitative estimate risk matrix. Such hazards were assessed as low, moderate or high. Vulnerabilities were identified using a checklist to this purpose, detecting those related to area design, treatment of waste and the biosafety organization, which established the existence of critical points within the production process with high and moderate risk(AU)

Respuesta inmune y alergia a vacunas / Immune response and allergies to vaccines

Las vacunas son altamente efectivas en prevenir enfermedades infecciosas a través del desarrollo en el individuo de una respuesta inmune protectora, sin desarrollar la enfermedad. Los distintos tipos de vacunas producen diferentes tipos de respuestas inmunes y variadas estrategias se han desarrollado para mejorar esta respuesta. El sistema inmune sufre cambios con la edad y esta inmunosenecencia altera la capacidad de responder frente a ellas. Por otro lado, si bien el sistema inmune puede reconocer elementos presentes en las vacunas y montar respuestas de hipersensibilidad ante ellos, las alergias a las vacunas son raras, teniendo que distinguirlas adecuadamente de otro tipo de reacciones. En caso que un paciente presente una reacción compatible con alergia, es importante conocer todos los componentes de la vacuna para realizar un estudio adecuado.

Vaccines are highly effective in preventing infectious diseases through the development in the individual a protective immune response, without developing the disease. Different types of vaccines produce different types of immune responses, and varied strategies have been developed to improve this response. The immune system undergoes changes with age, and this inmunosenescence alters the ability to respond to them. On the other hand, although the immune system can recognize elements present in vaccines and establish hypersensitivity responses to them, vaccine allergies are rare, having to properly distinguish them from other types of reactions. In the event that a patient has an allergy-compatible reaction, it is important to know all the components of the vaccine to conduct a proper study.

Inmunizaciones en niños, adolescentes y adultos inmunosuprimidos / Immunizations in children, adolescent and adult immunocompromised hosts

Los pacientes inmunosuprimidos presentan un riesgo mayor de infecciones, debido a sus disfunciones inmunes, producto de la actividad de su enfermedad y la terapia inmunosupresora. El uso de vacunas disminuye este riesgo, otorgando protección directa e indirecta, a través de la vacunación del paciente y sus contactos. Las vacunas inactivadas han demostrado un perfil de seguridad adecuado en estos pacientes, por lo que no están contraindicadas, aunque su respuesta inmune puede ser inadecuada. Las vacunas vivas atenuadas, formalmente contraindicadas, poseen una información creciente que permite evaluar su riesgo/beneficio de manera individual. Por este motivo es necesario procurar mantener el calendario de vacunas actualizado y complementado, evitando el retraso en esquemas de vacunación y poniéndolo al día lo antes posible, con estrategias basadas en el individuo. Para llevar a cabo esto, se debe conocer y considerar los intervalos entre las vacunas, los esquemas acelerados, la solicitud de vacunas especiales, las aprobaciones vigentes y, finalmente, sus contraindicaciones.

Immunecompromised patients are at higher risk of infections due to their immune dysfunction caused by ongoing disease processes and immunosuppressive therapy. Patient vaccination or vaccination of the people in contact with patients diminishes their risk of infection. Although the immune response of immunocompromised patients might be impaired, the use of inactivated vaccines is safe and it is not contraindicated in these patients. Formerly, live attenuated vaccines were contraindicated in immunecompromised patients, but recently more data supports their use when evaluating case by case the risks and benefits of their application. Thus, it is important to keep and up-to-date, taylor-based and enhanced vaccination schedule in these cases. For this, specialists need to be informed about the availability of regular and special vaccines, their current approvals, vaccine administration protocols under specific situations and vaccine contraindications.

The effect of Spirulina algae on the immune response of SPF chickens to commercial inactivated Newcastle vaccine in poultry / El efecto del alga Spirulina sobre la respuesta inmune de pollos SPF inducida por la vacuna inactivada comercial contra la enfermedad de Newcastle

The objective of this study was to investigate the effects of Spirulina platensis (SP) powder supplementation on immune response in SPF chickens. For this purpose, 120 SPF chicks were randomly clustered into six groups consisting of 20 birds each which assigned to five groups vaccinated by commercial inactivated Newcastle disease (ND) vaccine at 21 days of age. The four groups were supplemented with 0.5, 1, 1.5 and 2 g of SP per kg of ration at 7 day of age and other group as control treatment group. Control unvaccinated group still without any treatment. Individual blood samples were collected weekly from all groups, and NDV-HI antibodies were measured using Hemagglutination inhibition (HI) test. After 28 days post-vaccination, ten birds from all groups were challenged intramuscularly at a dose 0.5 mL/bird containing 106 EID50 of local NDV genotype VII. Challenge virus shedding was detected using real time qrt-PCR of oropharyngeal swabs that were collected from all challenged chicken groups of at 3, 5, 7 and 10 days post challenge. Obtained results showed that vaccinated groups of SPF-chickens either supplied with Spirulina or control treatment group induced positive serological response as NDV-HI antibody were measured in sera of immunized chicks (7.6, 8, 8.3, 8.9 and 7.4 log2, respectively) at 4 weeks post vaccination (WPV). Significant differences were observed at 2 WPV in the vaccinated SPF chickens consumed 1, 1.5 and 2 g of SP/kg of ration, compared to untreated vaccinated group (p<0.05). Immunized SPF chickens supplied with different SP concentration confer satisfactory protection against heterologous challenge virus (90 percent, 100 percent, 100 percent and 100 percent respectively), in contrast to untreated vaccinated chickens. Different percentages of reduction of viral shedding (55 percent, 65 percent, 76 percent and 87 percent) of treated vaccinated chickens with different concentration of SP were detected, despite untreated group were reduced 46 percent from total viral shedding. These findings suggest that dietary Spirulina has immune-stimulatory effects on the immune system of SPF chickens. One gram from SP per kg of ration was minimum recommended concentration that able to exhibit optimum immune response, increase protection against heterologous strains and able to reduce viral shedding(AU)

El objetivo de este estudio fue investigar los efectos de la suplementación con polvo de Spirulina platensis (SP) sobre la respuesta inmune en pollos SPF. Para este propósito se agruparon al azar 120 polluelos SPF en seis grupos de 20 aves cada uno, que se asignaron a cinco grupos vacunados con la vacuna comercial inactivada contra la enfermedad de Newcastle (ND) a los 21 días de edad. Cuatro grupos se suplementaron con 0,5; 1; 1,5 y 2 g de SP por kg de ración a los 7 días de edad, un grupo vacunado sin suplemento y un grupo sin ningún tratamiento. Semanalmente, se recogieron muestras de sangre individuales de todos los grupos y se midieron los anticuerpos hemaglutinantes contra el virus Newcastle (NDV-HI) mediante la prueba de inhibición de la hemaglutinación (HI). 28 días después de la vacunación, fueron retadas diez aves de cada grupo por vía intramuscular a una dosis 106 EID50 del genotipo VII del NDV local en un volumen de 0,5 mL/ave. Se detectó la eliminación del virus mediante qrt-PCR en hisopos orofaríngeos que se recolectaron en todos los grupos a los 3, 5, 7 y 10 días después del reto. Los resultados obtenidos mostraron que los grupos vacunados de pollos y suplementados con Espirulina y el grupo de control vacunado, indujeron una respuesta serológica positiva cuando se determinaron los anticuerpos NDV-HI en los pollitos inmunizados (7,6; 8; 8,3; 8,9 y 7,4 log2 respectivamente) a las 4 semanas después de la vacunación (SPV). Se observaron diferencias significativas a las 2 SPV en los pollos vacunados que consumieron 1, 1,5 y 2 g de SP/kg de ración, en comparación con el grupo vacunado no tratado (p<0,05). Los pollos inmunizados que recibieron diferentes concentraciones de SP mostraron una protección satisfactoria contra el desafío heterólogo viral (90 por ciento, 100 por ciento y 100 por ciento respectivamente), en contraste con los pollos vacunados no tratados. Se observaron diferentes porcentajes de reducción de la diseminación viral (55 por ciento, 76 por ciento y 87 por ciento) entre los pollos vacunados tratados con diferente concentración de SP. En el grupo no tratado se redujo al 46 por ciento. Estos hallazgos sugieren que la Espirulina en la dieta tiene efectos inmunoestimuladores sobre el sistema inmunitario de los pollos. Un gramo de SP por kg de ración fue la concentración mínima recomendada para una respuesta inmune óptima, y de esta forma aumentar la protección contra las cepas heterólogas y disminuir la diseminación viral(AU)

Evaluation of protection against bovine viral diarrhea virus type 2 after vaccination of the calves with bovine viral diarrhea virus type 1 combo inactivated vaccine / Avaliação da proteção contra o vírus da diarreia viral bovina tipo 2 após vacinação de bezerros com vacina combinada inativada do vírus da diarreia viral bovina tipo 1

This study was designed to evaluate the extent of the protection for bovine viral diarrhea virus type 2 (BVDV-2) infection, afforded by vaccination with a combo inactivated vaccine, which contains bovine viral diarrhea virus type 1 (BVDV-1) and infectious bovine rhinotracheitis virus (IBRV). Five 3-4-month-old calves were intramuscularly vaccinated with a single dose of the combo vaccine and boosted with same dose three weeks after the first vaccination, with five mock immunized calves serving as a control group. Twenty-one days after the second vaccination, all calves were challenged with BVDV-2 SX08 strain by spray into nostril. The unvaccinated animals developed typical clinical signs of high rectal temperature, diarrhoea with erosions and a dramatic drop in leukocyte counts. These signs occured markedly less in all vaccinated animals, the rectal temperature, leukopenia and virarmia of which, were significantly less than the mock immunized calves. It can be concluded that vaccination with the combo inactivated vaccine affords cross-protection against clinical effects of a challenge-infection with BVDV-2 SX08 strain, although it was part protection.(AU)

Este estudo foi desenvolvido para avaliar a extensão da proteção contra a infecção pelo vírus da diarréia viral bovina tipo 2 (BVDV-2) através da vacinação com uma vacina combinada inativada contendo o vírus da diarréia viral bovina tipo 1 (BVDV-1) e vírus da rinotraqueíte de bovinos infecciosos (IBRV). Cinco bezerros com 3 a 4 meses de idade foram vacinados via intramuscular com uma dose única da vacina combinada e reforçados com a mesma dose três semanas após a primeira vacinação, com cinco bezerros imunizados em simulação servindo como grupo controle. Vinte e um dias após a segunda vacinação, todos os bezerros foram desafiados com a cepa BVDV-2 SX08 por spray na narina. Os animais não vacinados desenvolveram sinais clínicos típicos, como alta temperatura retal, diarréia com erosões e queda drástica na contagem de leucócitos. Estes sinais tiveram ocorrência significativamente menor em todos os animais vacinados, cuja temperatura retal, leucopenia e virarmia eram significativamente menores do que os bezerros simulados. É possível concluir que a vacinação com a vacina combinada inativada proporciona proteção cruzada contra os efeitos clínicos de uma infecção provocada pela cepa BVDV-2 SX08, embora tenha sido parcialmente protegida.(AU)

ISA 61 VG adjuvant enhances protective immune response of Listeria monocytogenes inactivated vaccine / 生物工程学报

Listeria monocytogenes (Lm) is zoonotic pathogen that can cause listeriosis, and vaccine is one of the effective methods to prevent this pathogen infection. In this study, we developed a novel vaccine that is a mixture of inactivated bacteria and Montanide™ ISA 61 VG, a mineral oil adjuvant, and evaluated the safety and immune response characteristics of this vaccine. The mice immunized with the ISA 61 VG adjuvant had high safety, and it could induce significantly higher titer of anti-listeriolysin O (LLO) antibody and higher value of IgG2a/IgG1 ratio compared with the group without the adjuvant. In particular, it could provide 100% immune protection against lethal doses of Lm challenge in mice. In summary, ISA 61VG adjuvant significantly enhanced the ability of inactivated listeria vaccine to induce humoral and cellular immune responses, thereby enhanced the protective immune response in the host, and it is a potential vaccine candidate for the prevention of Lm infection in humans and animals.

Cumulative inactivated vaccine exposure and allergy development among children: a birth cohort from Japan

BACKGROUND@#Adjuvants used in inactivated vaccines often upregulate type 2 immunity, which is dominant in allergic diseases. We hypothesised that cumulative adjuvant exposure in infancy may influence the development of allergies later in life by changing the balance of type 1/type 2 immunity. We examined the relationship between immunisation with different vaccine types and later allergic disease development.@*METHODS@#We obtained information regarding vaccinations and allergic diseases through questionnaires that were used in The Japan Environment and Children's Study (JECS), which is a nationwide, multicentre, prospective birth cohort study that included 103,099 pregnant women and their children. We examined potential associations between the initial vaccination before 6 months of age and symptoms related to allergies at 12 months of age.@*RESULTS@#Our statistical analyses included 56,277 children. Physician-diagnosed asthma was associated with receiving three (aOR 1.395, 95% CI 1.028-1.893) or four to five different inactivated vaccines (aOR 1.544, 95% CI 1.149-2.075), compared with children who received only one inactivated vaccine. Similar results were found for two questionnaire-based symptoms, i.e. wheeze (aOR 1.238, 95% CI 1.094-1.401; three vaccines vs. a single vaccine) and eczema (aOR 1.144, 95% CI 1.007-1.299; four or five vaccines vs. a single vaccine).@*CONCLUSIONS@#Our results, which should be cautiously interpreted, suggest that the prevalence of asthma, wheeze and eczema among children at 12 months of age might be related to the amount of inactivated vaccine exposure before 6 months of age. Future work should assess if this association is due to cumulative adjuvant exposure. Despite this possible association, we strongly support the global vaccination strategy and recommend that immunisations continue.@*TRIAL REGISTRATION@#UMIN000030786 .

Vacinas experimentais para febre amarela como modelo de estudo de novos adjuvantes / Experimental yellow fever vaccines as a study model for new adjuvants

A vacina de febre amarela atenuada é uma das mais bem-sucedidas já desenvolvidas. Entretanto, restrições de administração para pacientes imunodeprimidos e raros eventos adversos associados são desvantagens que motivam o desenvolvimento de vacinas mais seguras. À medida que aumenta a segurança, a imunogenicidade diminui na ausência de replicação viral. Nesse contexto, adjuvantes são elementos chave na ativação da imunidade inata para modulação das respostas adaptativas e proteção. Adjuvantes de diferentes naturezas e mecanismos de ação têm sido estudados: imunoestimuladores como agonistas de TLR, carreadores de antígenos e agentes de efeito depósito. Nesse estudo pretendemos identificar adjuvantes promissores para o desenvolvimento de novos candidatos vacinais para febre amarela. Para isso, camundongos C57BL/6 foram imunizados com diferentes formulações de antígenos modelo (vírus inativado e proteínas de envelope recombinantes produzidas em diferentes sistemas de expressão) com os adjuvantes: Al(OH)3; Addavax (emulsão baseada em esqualeno); combinações de Al(OH)3 e Flagelina FliC (agonista de TLR5); e CAF01 (nanopartícula) em esquema de 2 doses (D0 e D28) ou 3 doses (D0, D14 e D28). Após a imunização, os camundongos foram desafiados com inóculo letal do vírus de febre amarela por via intracerebral para determinar as taxas de sobrevivência. Os soros foram analisados por ELISA e PRNT50 para detecção dos títulos de IgG total e anticorpos neutralizantes

O vírus FA17DD inativado apresentou o melhor desempenho como antígeno modelo, sendo capaz de induzir 100% de proteção ao desafio após imunização com 2 doses na formulação com o adjuvante Addavax e 70% de proteção na formulação com hidróxido de alumínio. Os demais adjuvantes avaliados (Al(OH)3/ Flagelina FliC e CAF01) não foram capazes de gerar incremento de proteção com os antígenos avaliados. As formulações experimentais com melhor desempenho (FA17DD inativado/Addavax e FA17DD inativado/Al(OH3) foram avaliadas em um segundo ensaio para melhor caracterização das respostas imunológicas envolvidas na proteção. Ambas foram capazes de induzir apenas níveis basais de anticorpos neutralizantes; porém altos títulos de IgG para o vírus da febre amarela com predomínio do subtipo IgG1. A caracterização das respostas celulares locais (ELISpot citocinas e células B) no sítio de inoculação nos tempos pré e pós-desafio revelou níveis superiores de IFNγ nos animais sobreviventes. Após o desafio, todos os animais sobreviventes apresentaram altos títulos de anticorpos neutralizante e IgG total, com incremento do subtipo IgG2a. O uso de Addavax como adjuvante para vacinas não vivas para febre amarela surge como uma alternativa promissora de induzir proteção com menor número de doses. A aplicação do modelo de desafio murino para febre amarela na avaliação de novos adjuvantes se mostrou uma abordagem promissora para a avaliação de novos adjuvantes para uso neste modelo, bem como na geração de conhecimentos extrapoláveis para outros candidatos vacinais em desenvolvimento. (AU)

Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil

Abstract The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines.In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18–60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed.A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults.The study showed that inactivated quadrivalent influenza vaccine was immunogenic and well-tolerated in Brazilian adults and older adults.

Molecular stability of a vaccine strain of Canine coronavirus after serial passages in A72 cells / Estabilidade molecular de uma amostras vacinal de Coronavírus canino após passagens seriadas em células A72

Canine coronavirus (CCoV) exists in types I and II and infects dogs leading mainly to enteritis, though type II has already been associated with generalized and highly lethal infection. A CCoV-type II inactivated vaccine produced in A72 canine cells is available worldwide and largely used, though the molecular stability after serial passages of vaccine seeds is unknown. This article reports the evolution of the CCoV-II vaccine strain 1-71 in A72 cells based on partial S gene sequencing, showing the predominance of neutral evolution and the occurrence of four sites under purifying selection. Thus, cell-adapted strains of CCoV-II may be genetically stable after serial passages in a same cell line due to a stable virus-host relationship.(AU)

O Coronavírus canino (CCoV) ocorre como tipos I e II e infecta cães, levando principalmente a enterite, apesar do tipo II já ter sido associado à infecção generalizada e altamente letal. Uma vacina de CCoV-II inativada produzida em células caninas A72 é disponível mundialmente e largamente utilizada, apesar da sua estabilidade molecular após passagens seriadas de sementes vacinais ser desconhecida. Este artigo relata a evolução da amostra vacinal CCoC-II 1-71 em células A-72 com base em sequenciamento parcial do gene S, demonstrando predomínio de evolução neutra e a ocorrência de quaro sítios sob seleção purificante. Portanto, amostras de CCoV-II adaptadas a cultivos celulares podem ser estáveis geneticamente após passagens seriadas em uma mesma linhagem celular devido à existência de uma relação estável vírus-hospedeiro.(AU)

Development and trial of vaccines against Brucella

The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most successful vaccine (S19) is only used in calves, as adult vaccination results in orchitis in male, prolonged infection, and possible abortion complications in pregnant female cattle. Another widely deployed vaccine (RB51) has a low protective efficacy. An ideal vaccine should exhibit a safe profile as well as enhance protective efficacy. However, currently available vaccines exhibit one or more major drawbacks. Smooth live attenuated vaccines suffer shortcomings such as residual virulence and serodiagnostic interference. Inactivated vaccines, in general, confer relatively low levels of protection. Recent developments to improve brucellosis vaccines include generation of knockout mutants by targeting genes involved in metabolism, virulence, and the lipopolysaccharide synthesis pathway, as well as generation of DNA vaccines, mucosal vaccines, and live vectored vaccines, have all produced varying degrees of success. Herein, we briefly review the bacteriology, pathogenesis, immunological implications, candidate vaccines, vaccinations, and models related to Brucella.

Reappraisal of the Immunogenicity and Safety of Three Hepatitis A Vaccines in Adolescents

Although the overall incidence of hepatitis A in Korea has been decreasing, adolescents remain highly vulnerable to its outbreaks. This study was conducted to compare the immunogenicity and safety of three hepatitis A vaccines in Korean adolescents. Healthy anti-hepatitis A virus seronegative subjects aged 13 to 19 yr were randomized in three equal groups to receive two doses of Avaxim(TM), Epaxal(R), or Havrix(R), 6 to 12 months apart. Seroconversion rates one month after the first dose were 98%, 95%, and 93% for Avaxim(TM), Epaxal(R), and Havrix(R), respectively. Seroconversion rates reached 100% for all vaccine groups one month after the second dose. Anti-HAV geometric mean concentrations (GMCs) were 7,207.7 mIU/mL (95% CI, 6023.1-8684.7), 1,750.5 mIU/mL (95% CI, 1362.9-2248.3), and 1,953.5 mIU/mL (95% CI, 1459.4-2614.7) after two doses of Avaxim(TM), Epaxal(R), and Havrix(R) respectively. Avaxim(TM) was significantly more immunogenic than Epaxal(R) and Havrix(R), whereas there were no significant differences in antibody responses between Epaxal(R) and Havrix(R). Local and systemic solicited adverse events (AEs) were mostly of mild-to-moderate intensity and resolved within 5 days. No serious AEs were reported. In conclusion, all three vaccines are highly immunogenic and well-tolerated in Korean adolescents. (Clinical Trial Registry NCT00483470)

Improved immunogenicity of Newcastle disease virus inactivated vaccine following DNA vaccination using Newcastle disease virus hemagglutinin-neuraminidase and fusion protein genes

The present study describes the development of DNA vaccines using the hemagglutinin-neuraminidase (HN) and fusion (F) genes from AF2240 Newcastle disease virus strain, namely pIRES/HN, pIRES/F and pIRES-F/HN. Transient expression analysis of the constructs in Vero cells revealed the successful expression of gene inserts in vitro. Moreover, in vivo experiments showed that single vaccination with the constructed plasmid DNA (pDNA) followed by a boost with inactivated vaccine induced a significant difference in enzyme-linked immunosorbent assay antibody levels (p < 0.05) elicited by either pIRES/F, pIRES/F+ pIRES/HN or pIRES-F/HN at one week after the booster in specific pathogen free chickens when compared with the inactivated vaccine alone. Taken together, these results indicated that recombinant pDNA could be used to increase the efficacy of the inactivated vaccine immunization procedure.

Assessment of the safety and efficacy of low pathogenic avian influenza (H9N2) virus in inactivated oil emulsion vaccine in laying hens

In Korea, several outbreaks of low pathogenic AI (H9N2) viral infections leading to decreased egg production and increased mortality have been reported on commercial farms since 1996, resulting in severe economic losses. To control the H9N2 LPAI endemic, the Korea Veterinary Authority has permitted the use of the inactivated H9N2 LPAI vaccine since 2007. In this study, we developed a killed vaccine using a low pathogenic H9N2 AI virus (A/chicken/Korea/ADL0401) and conducted safety and efficacy tests in commercial layer farms while focusing on analysis of factors that cause losses to farms, including egg production rate, egg abnormality, and feed efficiency. The egg production rate of the control group declined dramatically 5 days after the challenge. There were no changes in feed consumption of all three groups before the challenge, but rates of the control declined afterward. Clinical signs in the vaccinated groups were similar, and a slight decline in feed consumption was observed after challenge; however, this returned to normal more rapidly than the control group and commercial layers. Overall, the results of this study indicate that the safety and efficacy of the vaccine are adequate to provide protection against the AI field infection (H9N2) epidemic in Korea.