Enlightening from optimizing post-authorization safety monitoring system of SARS-CoV-2 vaccines in major economies worldwide / 中华预防医学杂志

Ongoing global pandemic of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has promoted the unprecedented rapid development and large-scale rolling out of different platform-based COVID-19 vaccines worldwide. How to effectively respond to the expected scale increasing adverse events after vaccination campaign of COVID-19 vaccines is a common problem faced by the world. A lot of countries and regions around the world have arranged in advance at different levels, optimizing the original vaccine safety monitoring system from the perspectives of strengthening the foundation and capabilities, promoting internal and external cooperation, upgrading methods, as well as improving transparency and public communication, which has ensured the good and efficient operation of the system and can provide reference for the construction of relevant fields in China.

Percepción del riesgo biológico en el proceso productivo de la vacuna contra la peste porcina clásica / Biological risk perception in the production process of classical swine fever vaccine

La existencia de agentes biológicos como el virus de la peste porcina clásica para la producción de vacunas veterinarias, entre otros de igual importancia para nuestro país y la región en general, justifica una buena gestión de la seguridad biológica, ya que el desconocimiento del riesgo por parte del personal que labora en estas vacunas puede provocar contaminaciones de graves consecuencias medio ambientales, en el proceso de producción y a nivel personal si son causantes de accidentes fatales. El objetivo de la investigación fue realizar un análisis de la percepción de riesgo existente en el personal responsable del proceso de producción de la vacuna contra la peste porcina clásica. La aplicación del RISKPERCEP en el personal de la instalación de producción de la vacuna de la peste porcina clásica mostró como resultados el comportamiento de diferentes variables que hacen evidente la alta subestimación del riesgo existente en el personal evaluado y que existe la necesidad de profundizar en la formación en bioseguridad para todo el personal que labora en el proceso. Finalmente, se relacionan estos temas y su importancia para mejorar la calidad de la producción en estos procesos, así como incrementar el conocimiento acerca del riesgo biológico a todos los niveles(AU)

The existence of high-risk biological agents such as the classical swine fever virus for the production of veterinary vaccines, among others of equal importance for our country and the region in general, justifies good management of biological safety, since ignorance of the risk on part of the personnel who work in them, can cause contamination with serious consequences both at personal and environmental level, causing fatal accidents. The objective of the research was to carry out an analysis of the perception of existing risk in the personnel responsible for the production process of the vaccine against classical swine fever. The application of RISKPERCEP in the classical swine fever vaccine production facility showed as results the behavior of different variables that make evident the high underestimation of the existing risk in the evaluated personnel and that there is a need to deepen the training in biosafety to all staff working in the process. Finally, these issues and their importance to improve the quality of production in these processes are related, as well as to increase knowledge about biological risk at all levels(AU)

Consideraciones sobre los eventos trombóticos posteriores a la administración de la vacuna de AstraZeneca contra COVID-19 en Europa / Considerations for Thrombotic Events Following AstraZeneca COVID-19 Vaccine Administration in Europe

En las campañas de vacunación, como en la actual situación de COVID-19, es habitual que los países señalen posibles efectos adversos después de la vacunación. Esto no significa necesariamente que los eventos estén relacionados con la vacunación en sí, pero es necesario investigarlos. También muestra que el sistema de vigilancia funciona y que existen controles efectivos. La Organización Mundial de la Salud (OMS) está en contacto regular con la Agencia Europea de Medicamentos (EMA) y otras autoridades reguladoras del mundo para obtener la información más reciente sobre la seguridad de todas las vacunas para COVID-19.

Assessment of the pathogenicity of cell-culture-adapted Newcastle disease virus strain Komarov

Newcastle disease vaccines hitherto in vogue are produced from embryonated chicken eggs. Egg-adapted mesogenic vaccines possess several drawbacks such as paralysis and mortality in 2-week-old chicks and reduced egg production in the egg-laying flock. Owing to these possible drawbacks, we attempted to reduce the vaccine virulence for safe vaccination by adapting the virus in a chicken embryo fibroblast cell culture (CEFCC) system. Eighteen passages were carried out by CEFCC, and the pathogenicity was assessed on the basis of the mean death time, intracerebral pathogenicity index, and intravenous pathogenicity index, at equal passage intervals. Although the reduction in virulence demonstrated with increasing passage levels in CEFCC was encouraging, 20% of the 2-week-old birds showed paralytic symptoms with the virus vaccine from the 18^th(final) passage. Thus, a tissue-culture-adapted vaccine would demand a few more passages by CEFCC in order to achieve a complete reduction in virulence for use as a safe and effective vaccine, especially among younger chicks. Moreover, it can be safely administered even to unprimed 8-week-old birds.

Toxic Epidermal Necrolysis with Ocular Involvement Following Vaccination for Hemorrhagic Fever with Renal Syndrome

We report a case of toxic epidermal necrolysis with ocular involvement following vaccination for hemorrhagic fever with renal syndrome. A healthy 20-year-old male soldier presented with confluent purpuric and erythematous dusky red macules evolving to flaccid blister and epidermal detachment on the whole body with conjunctival injection. The patient had no antecedent medical or surgical conditions except for two doses of hemorrhagic fever with renal syndrome vaccination. With supportive care, skin lesions were improved. Ophthalmic examinations revealed conjunctival injection with epithelial defects in both eyes. Ocular complications were resolved after amniotic membrane transplantation. Toxic epidermal necrolysis may be considered as a possible complication of hemorrhagic fever with renal syndrome vaccination.

Vacuna contra la fiebre hemorrágica argentina Candid#1 producida en la Argentina: Inmunogenicidad y seguridad / Candid#1 vaccine against Argentine Hemorrhagic Fever produced in Argentina: Immunogenicity and safety

Se realizó un estudio clínico en 946 voluntarios humanos sanos, donde se comparó la vacuna Candid#1 producida en Argentina con la elaborada en EE.UU., que había sido utilizada en estudios previos. Como objetivo primario se evaluó la equivalencia en la eficacia utilizando como marcador subrogante a la inmunogenicidad medida por detección de anticuerpos neutralizantes. Como objetivo secundario se evaluó la equivalencia en inocuidad comparando las tasas de reacciones adversas. Ambas vacunas mostraron una tasa equivalente de inmunogenicidad ligeramente superior al 95.5%, que es la eficacia estimada para Candid #1 en estudios previos. No se observaron eventos adversos graves relacionados con la vacuna. Los eventos adversos generales considerados relacionados fueron de escasa significación clínica y de resolución espontánea o con tratamiento sintomático; se presentaron en los receptores de ambas vacunas en tasas equivalentes (29.9% para la vacuna fabricada en la Argentina y 35.0% para la fabricada en EE.UU.), e incluyeron: cefalea, decaimiento, mialgias, plaquetopenia leve (< 150 000 plaquetas/mm³), náuseas y/o vómitos, leucopenia leve (< 4 000 blancos/mm³), fiebre, dolor retroocular, mareos, microhematuria, lumbalgia y exantema. Estos resultados indican que la vacuna Candid #1 elaborada en la Argentina es equivalente a la elaborada en los EE.UU. Este estudio permitió el registro del biológico producido en la Argentina ante la autoridad regulatoria del país (ANMAT).

A clinical study in 946 human volunteers was done to compare Candid #1 vaccine manufactured in Argentina with the vaccine produced in USA that had been previously used. The efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. Safety was evaluated comparing the rate of adverse events. Both vaccines showed a comparable rate of seroconversion, slighty higher than the efficacy estimated from previous studies (95.5%). There were no severe adverse events related to the vaccines. The general events considered related to the vaccines were not clinically relevant and disappeared either spontaneously or with symptomatic treatment. Similar rates of adverse events (29.9% for the Argentine vaccine and 35.0% for the USA vaccine) were found for both vaccines. These included: headache, weakness, myalgias, mild low blood cell (< 4 000/mm³) and platelet (< 150 000/mm³) counts, nausea and/or vomiting, fever, retroocular pain, dizziness, microhematuria, low backache and exantema. These results indicate that the vaccine Candid#1 manufactured in Argentina is equivalent to the manufactured in USA. These results allowed the National Institute of Human Viral Diseases (INEVH) to register the vaccine produced locally under the National Regulatory Authority (ANMAT).

Avaliação de diferentes vias vacinais para vacinação contra o vírus da doença de Newcastle em aves de fundo de quintal / Assessment of different vaccination approaches against Newcastle disease virus in domestic backyard poultry

Foram avaliadas três vias de aplicação vacinal contra o vírus da doença de Newcastle em aves de criatório de fundo de quintal (AFQ) jovens e adultas. Um total de 135 AFQ foram distribuídas em tratamentos distintos de acordo com a via vacinal: via ocular (VO), água de bebida (VAB) e alimentar (VA). Cada tratamento foi representado por 40 aves (20 jovens e 20 adultas) e utilizou-se um grupo-controle de 15 aves não vacinadas. O programa de vacinação estabelecido constou de uma primovacinação e dois reforços vacinais, utilizando-se a cepa La Sota. Para aves jovens, os títulos obtidos pelas VO e VAB não diferiram aos 15, 45 e 140 dias, mas houve diferenças nos títulos das aves vacinadas pela VA. Nas aves adultas, a vacinação pela VO apresentou resultados mais elevados que as vacinações pelas VAB e VA na primeira resposta, aos 15 dias. Aos 45 dias, os títulos obtidos pela VAB foram mais baixos que os obtidos pela VO, e, aos 140 dias, não houve diferença entre as três vias avaliadas. Concluiu-se que as vacinações pelas VO e VAB constituem alternativas eficazes para vacinação de AFQ jovens e adultas.

Three ways of vaccination against Newcastle Disease Virus (NDV) were evaluated in young and adults domestic backyard poultry (DBP). A total of 135 DBP was submitted to three different administration routes of ND vaccine: eye-drop, drinking water, and feed. Each treatment consisted of 40 birds (20 young and 20 adult) and a control group of 15 unvaccinated birds. The treatment consisted of a first vaccination and two boosters, using La Sota strain. For young birds, the eye-drop and drinking water vaccinations presented no differences at 15, 45, and 140 days, differing from the titers obtained by birds treated by feed vaccination method. In the adult birds, the eye-drop administration presented higher titers than by drinking water and feed approaches in the first response to the vaccination at 15 days. At 45 days, the results obtained by the drinking water had lower titers than those from the eye-drop. The three vaccination methods presented no difference at 140 days. In conclusion, the vaccination by eye-drop and drinking water methods constituted an efficient alternative of vaccination for adult and young DBP against Newcastle virus.

Vacunas anti-rotavirus: al fin una realidad / New rotavirus vaccines: a reality at last

Rotavirus es la primera causa de diarrea aguda grave en niños bajo 3 años de edad en el mundo. Esta infección es responsable de 25 millones de consultas, 2 millones de hospitalizaciones y 440.000 muertes por año en niños con menos de 5 años. El desarrollo de vacunas anti-rotavirus ha sido un camino largo y tortuoso marcado por la abrupta caída de Rotashield® en 1999 debido a su asociación con invaginación intestinal. Luego de seis años de intensa investigación, el mundo celebra la licencia de dos nuevas vacunas que, a pesar de ser diferentes en su formulación y forma de administración, han demostrado ser seguras y no asociadas a invaginación intestinal, en estudios de Fase III de gran magnitud, que enrolaron más de 60.000 niños. Estas dos vacunas, Rotarix® de Glaxo SmithKline Biologicals y Rotateq® de Merck Sharp & Dohme son altamente eficaces contra diarrea grave causada por rotavirus de los serotipos más prevalentes en el mundo. La incorporación de estas vacunas, más temprano que tarde, especialmente en los países más pobres del mundo, requerirá de un esfuerzo conjunto de los gobiernos, laboratorios productores, organismos internacionales y no gubernamentales y fundaciones de beneficencia.

Response to JE vaccine among HIV-infected children, Bangkok, Thailand.

Since 1990, Japanese encephalitis (JE) vaccine has been part of EPI in northern Thailand, where there is a high prevalence of JE and HIV infection. To evaluate the immunogenicity and safety of JE vaccine among HIV-infected children, we conducted a retrospective study of HIV-infected and uninfected children who received 2 doses of JE vaccine at 12 months of age. Pre- and post-immunization plasma specimens were tested by plaque reduction neutralization for antibody levels to JE and dengue(1-4) viruses; titers of > or =10 were considered positive. Excluding 5 children with preimmunization antibodies, 5 of 14 (36%) HIV-infected children and 18 of 27 (67%) uninfected children had positive JE antibody titers after immunization [odds ratio (OR) 0.3, p=0.06]; 31% absolute difference [95% confidence interval (CI) 0-61.7%). The geometric mean titer of HIV-infected children with positive titers was lower than that of control children (15.1 vs, 23.8; p=0.17). No significant vaccine-associated adverse events were noted. We conclude that primary antibody response to JE vaccine was low among HIV-infected children and was approximately half of that seen among uninfected children. In endemic areas, HIV-infected children are likely to be at risk of acquiring JE despite routine immunization with 2 doses.

Imunoprofilaxia nas hepatites virais / Immunoprophylaxis for viral hepatitis

Um breve relato atualizado da imunoprofilaxia das hepatites virais é apresentado como guia para imunizaçäo, informando sobre tipos, doses, esquemas de administraçäo e apresentaçöes comerciais das vacinas contra hepatite A e B, com abreviadas consideraçöes sobre a fisiopatologia e imunopatologia das doenças respectivas.

A field study on Nakayama and Beijing strains of Japanese encephalitis vaccines.

A field study to compare the immune response of children aged 1-6 years to Nakayama and Beijing strains JE vaccines was carried out in Mae Hong Son Province, northwest Thailand, where there was low incidence of JEV infection. The first and second dose of each vaccine was given 1-2 weeks apart and the third dose was 1 year after the second dose. Seroconversion rate was similarly high, about 94% in both groups of vaccinees. At 6 and 12 months after 2 doses of vaccines, the seroconversion rates dropped in both groups of vaccinees, so there were 10-20% of children (50-65% if cross protection was considered) susceptible to JEV infections during this period. After the third dose of vaccine, the seroconversion rate rose to 100% in both groups. The GMT in Bejing strain vaccinees were slightly higher than Nakayama strain JE vaccines. To reduce the number of susceptible children during 6-12 months after the second dose and for longer protection, the primary JE immunization should be 3 doses and the timing for the third dose should be at 6 months after the second dose. Either Nakayama or Beijing strain vaccine could be used in Thailand.

Serological response to Japanese encephalitis vaccine in a group of school children in South Arcot district of Tamil Nadu.

A trial with Biken Japanese encephalitis (JE) vaccine made in Japan was carried out in South Arcot district of Tamil Nadu state, India. A total of 113 school children were included in the trial. The efficacy (as determined by serological response) and safety of the vaccine were evaluated. Side effects, though minor, were noted in 54.9 per cent of the children after each dose. The serum antibody titres were determined by mouse neutralization test, plaque reduction neutralization test and haemagglutination inhibition test. An antibody response to two-dose primary vaccination schedule was observed in 72.7 per cent, whereas 87.8 per cent of the vaccines responded positively after the booster dose administered one year after. Only about 20 per cent of the children had persisting antibodies one year after the primary vaccination. The results indicated a probable need of the third dose in the primary vaccination schedule.

Pattern of amino acids and proteins of blood serum in vaccinated chickens with gumboro disease vaccine

Twenty blood samples were taken from 10 vaccinated chickens with Gumboro disease virus [vaccine strain] and from other 10 non- vaccinated [control] chickens, serum was separated for determination of free amino acids, total protein and protein fractions. Recorded results concerning free amino acids revealed that there was a very highly significant decrease in tyrosine level, high significant decrease in the levels of proline, cysteine, valine and phenylalanine, significant decrease of lysine concentration. Whereas, the level of glutamic acid showed a highly significant increase in samples collected one day post vaccination with Gumboro vaccine. The amino acids [threonine, serine and valine] showed very high significant decreased levels. Both methionine and lysine were significantly decreased. While, glutamic acid showed significant increased value. Serum proteins showed a significant decrease in total protein level which associated also with a very high significant decrease of albumin fraction. In contrast, alpha globulin fraction revealed a very high significant increase, the A/G ratio was decreased in samples collected one day post vaccination with Gumboro vaccine. Ten days post vaccination, total protein showed a high significant decrease in accordance with the very high significant decrease of albumin fraction. But both alpha and gamma globulin fractions showed a very high significant increase, compared with their control values. The A/G ratio was decreased

The neurovirulence of flaviviruses in crab-eating monkeys (Macaca fascicularis).

The neurovirulent properties of attenuated dengue-2 and yellow fever (YF) vaccines, dengue-2 (DEN-2) and Japanese encephalitis (JE) viruses were studied in crab-eating monkeys (Macaca fascicularis). Number of central nervous system sites (as proportion affected) with neurovirulence (NV) lesions were compared. The results indicate that these monkeys reliably developed NV-lesion when inoculated with either JE or YF vaccine viruses (87%). NV-lesions occurred in a minority when inoculated with DEN-2 vaccine virus, were of minimal severity (9%), were probably biologically insignificant, and were of equal or less severity than lesions produced by its parental virus (10%).