ABSTRACT
Technological innovations in vaccinology have recently contributed to bring about novel insights for the vaccine-induced immune response. While the current protocols that use peripheral blood samples may provide abundant data, a range of distinct components of whole blood samples are required and the different anticoagulant systems employed may impair some properties of the biological sample and interfere with functional assays. Although the interference of heparin in functional assays for viral neutralizing antibodies such as the functional plaque-reduction neutralization test (PRNT), considered the gold-standard method to assess and monitor the protective immunity induced by the Yellow fever virus (YFV) vaccine, has been well characterized, the development of pre-analytical treatments is still required for the establishment of optimized protocols. The present study intended to optimize and evaluate the performance of pre-analytical treatment of heparin-collected blood samples with ecteola-cellulose (ECT) to provide accurate measurement of anti-YFV neutralizing antibodies, by PRNT. The study was designed in three steps, including: I. Problem statement; II. Pre-analytical steps; III. Analytical steps. Data confirmed the interference of heparin on PRNT reactivity in a dose-responsive fashion. Distinct sets of conditions for ECT pre-treatment were tested to optimize the heparin removal. The optimized protocol was pre-validated to determine the effectiveness of heparin plasma:ECT treatment to restore the PRNT titers as compared to serum samples. The validation and comparative performance was carried out by using a large range of serum vs heparin plasma:ECT 1:2 paired samples obtained from unvaccinated and 17DD-YFV primary vaccinated subjects. Altogether, the findings support the use of heparin plasma:ECT samples for accurate measurement of anti-YFV neutralizing antibodies.
Subject(s)
Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Anticoagulants/blood , Blood Specimen Collection/methods , Cellulose/analogs & derivatives , Drug Monitoring/methods , Heparin/blood , Neutralization Tests , Vaccination , Yellow Fever Vaccine/administration & dosage , Yellow Fever/prevention & control , Yellow fever virus/immunology , Adolescent , Adult , Aged , Biomarkers/blood , Cellulose/chemistry , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Predictive Value of Tests , Reproducibility of Results , Viral Plaque Assay , Yellow Fever/blood , Yellow Fever/diagnosis , Yellow Fever/virology , Young AdultABSTRACT
In a recently published article in this journal, Massad et al. contraindicates yellow fever vaccination to persons 60 years or older, considering that the risk of serious adverse events is higher for this age class. The conclusion was based on the input of available data on age-related probabilities of developing serious adverse events in the United States, as well on other data not firmly established. We consider such contraindication inadequate, because the data input has limitations, higher letality of wild-type yellow fever infection in older adults, risk of introduction of yellow fever by travelers into new countries, lower risk of vaccine adverse events in revaccinated or immune people in endemic countries, and the experience of Brazil, with only one suspect case of associated viscerotropic disease in an individual older than 60 years. The model proposed by Massad et al. is useful but can lead to different conclusions, depending on the epidemiological context and individual risk profile.
Subject(s)
Yellow Fever Vaccine/administration & dosage , Yellow Fever Vaccine/adverse effects , Yellow Fever/prevention & control , Adolescent , Adult , Age Factors , Aged , Child , Child, Preschool , Humans , Middle Aged , Risk Assessment , VaccinationABSTRACT
Objetivo: Comparar a resposta sorológica induzida por formulaçöes com diferentes concentraçöes de vírus da vacina contra sarampo da cepa Biken CAM-70. Métodos: Crianças sadias de 9 a 18 meses de um centro de saúde do Rio de Janeiro, RJ, cujos responsáveis concordaram em participar, foram randomizadas em três grupos vacinados com concentraçöes de 5.000, 1.000 ou 200 CCID50 (50 por cento Tissue Culture Infective Dose). Os participantes e o pessoal da pesquisa ignoravam o tipo de vacina administrada. A avaliaçäo sorológica foi realizada pelo teste de reduçäo em plaque de lise. Duas análises intermediárias dos dados foram programadas. Resultados: Das 223 crianças recrutadas, 84 por cento completaram todos os procedimentos; 79 por cento tinham idade menor que 10 meses; 93 por cento näo tinham anticorpos contra sarampo no soro pré-vacinal. As proporçöes de soroconversäo (quadruplicaçäo das concentraçöes pré-vacinais) foram 82 por cento, 55 por cento e 37 por cento (p<0,0000), nos grupos vacinados com 5.000, 1.000 ou 200 CCID50, respectivamente. As diferenças nas concentraçöes médias de anticorpos pós-vacinais também foram substanciais e estatisticamente significativas (p<0,000). A soroconversäo (independente da formulaçäo da vacina) foi de 73 por cento nas crianças com 10 ou mais meses de idade e 53 por cento naquelas com menos de 10 meses. Conclusöes: Formulaçöes da vacina com concentraçöes inferiores a 5.000 CCID50 näo induziram soroconversäo satisfatória. O desempenho da vacina por faixa etária foi compatível com o observado em outros estudos com a vacina Biken CAM-70 e indica que uma proporçäo apreciável de crianças vacinadas aos 9 meses pode näo obter resposta imunológica plena
