Detection of post-vaccination enhanced dengue virus infection in macaques: An improved model for early assessment of dengue vaccines.

The need for improved dengue vaccines remains since the only licensed vaccine, Dengvaxia, shows variable efficacy depending on the infecting dengue virus (DENV) type, and increases the risk of hospitalization for severe dengue in children not exposed to DENV before vaccination. Here, we developed a tetravalent dengue purified and inactivated vaccine (DPIV) candidate and characterized, in rhesus macaques, its immunogenicity and efficacy to control DENV infection by analyzing, after challenge, both viral replication and changes in biological markers associated with dengue in humans. Although DPIV elicited cross-type and long-lasting DENV-neutralizing antibody responses, it failed to control DENV infection. Increased levels of viremia/RNAemia (correlating with serum capacity at enhancing DENV infection in vitro), AST, IL-10, IL-18 and IFN-γ, and decreased levels of IL-12 were detected in some vaccinated compared to non-vaccinated monkeys, indicating the vaccination may have triggered antibody-dependent enhancement of DENV infection. The dengue macaque model has been considered imperfect due to the lack of DENV-associated clinical signs. However, here we show that post-vaccination enhanced DENV infection can be detected in this model when integrating several parameters, including characterization of DENV-enhancing antibodies, viremia/RNAemia, and biomarkers relevant to dengue in humans. This improved dengue macaque model may be crucial for early assessment of efficacy and safety of future dengue vaccines.

Safety and immunogenicity of 17DD attenuated yellow fever vaccine in howler monkeys (Alouatta spp.).

BACKGROUND: Alouatta spp. are highly susceptible to yellow fever (YF) infection and develop an often fatal disease. The threat posed by an outbreak started in 2016 leads us to investigate vaccination as a potential tool in preventing YF in non-human primates (NHP). METHODS: Susceptible howler monkeys were immunized with three different concentrations of the human Brazilian commercial YF17DD vaccine. Post-vaccination viremia/RNAemia, immunogenicity, and safety were characterized. RESULTS: The vaccine did not produce YF clinical manifestations in any of the NHPs. After immunization, all animals seroconverted demonstrating the ability of the YF vaccine to induce humoral response in Alouatta species. CONCLUSIONS: The present work has demonstrated the safe and immunogenic profile of the existing YF 17DD vaccine in howler monkeys. This knowledge may support further studies with other susceptible monkey species and provide a possible solution for controlling epizootics and preventing the devastation of endangered species.

A prospective, multicentre, cohort study to assess the incidence of dengue illness in households from selected communities in Brazil (2014-2018).

OBJECTIVES: To estimate the incidence of dengue infection across geographically distinct areas of Brazil. METHODS: This prospective, household-based, cohort study enrolled participants in five areas and followed them up for up to 4 years (2014-2018). Dengue seroprevalence was assessed at each scheduled visit. Suspected dengue cases were identified through enhanced passive and active surveillance. Acute symptomatic dengue infection was confirmed through reverse-transcriptase quantitative polymerase chain reaction in combination with an antigenic assay (non-structural protein 1) and serology. RESULTS: Among 3300 participants enrolled, baseline seroprevalence was 76.2%, although only 23.3% of participants reported a history of dengue. Of 1284 suspected symptomatic dengue cases detected, 50 (3.9%) were laboratory-confirmed. Based on 8166.5 person-years (PY) of follow-up, the incidence of laboratory-confirmed symptomatic infection (primary endpoint) was 6.1 per 1000 PY (95% confidence interval [CI]: 4.5, 8.1). Incidence varied substantially in different years (1.8-7.4 per 1000 PY). The incidence of inapparent primary dengue infection was substantially higher: 41.7 per 1000 PY (95% CI: 31.1, 54.6). CONCLUSIONS: Our findings, highlighting that the incidence of dengue infection is underestimated in Brazil, will inform the design and implementation of future dengue vaccine trials. CLINICAL TRIAL REGISTRATION: NCT01751139.

Evidence for interferon production and its correlation with YF 17DD vaccine virus yields in primary chick embryo cells.

Early experiments have resulted in the establishment of an efficient methodology for the production of a yellow fever vaccine in chicken embryo fibroblasts (CEF) using the 17DD virus strain [Freire, M.S., Mann, G.F., Marchevsky, R.S., Yamamura, A.M., Almeida, L.F., Jabor, A.V., Malachias, J.M., Coutinho, E.S., Galler, R., 2005. Production of yellow fever 17DD vaccine virus in primary culture of chicken embryo fibroblasts: yields, thermo and genetic stability, attenuation and immunogenicity. Vaccine 23, 2501-2512]. To investigate the role of the interferon system in vaccine virus yields, CEF cultures seeded at high and low cell densities and infected with the yellow fever 17DD virus were used. The supernatants of these cultures were tested for the presence of interferon by an assay based on the reduction of cytopathic effect of a challenge virus (Sindbis), for the enzymatic activity of the interferon-induced 2',5'-oligoadenylate synthetase and for the expression of 2',5'-oligoadenylate synthetase mRNA. The presence of interferon and its influence in the replication of yellow fever 17DD virus in CEF cultures was clearly demonstrated.

Characterization of recent and minimally passaged Brazilian dengue viruses inducing robust infection in rhesus macaques.

The macaque is widely accepted as a suitable model for preclinical characterization of dengue vaccine candidates. However, the only vaccine for which both preclinical and clinical efficacy results were reported so far showed efficacy levels that were substantially different between macaques and humans. We hypothesized that this model's predictive capacity may be improved using recent and minimally passaged dengue virus isolates, and by assessing vaccine efficacy by characterizing not only the post-dengue virus challenge viremia/RNAemia but also the associated-cytokine profile. Ten recent and minimally passaged Brazilian clinical isolates from the four dengue virus serotypes were tested for their infectivity in rhesus macaques. For the strains showing robust replication capacity, the associated-changes in soluble mediator levels, and the elicited dengue virus-neutralizing antibody responses, were also characterized. Three isolates from dengue virus serotypes 1, 2 and 4 induced viremia of high magnitude and longer duration relative to previously reported viremia kinetics in this model, and robust dengue virus-neutralizing antibody responses. Consistent with observations in humans, increased MCP-1, IFN-γ and VEGF-A levels, and transiently decreased IL-8 levels were detected after infection with the selected isolates. These results may contribute to establishing a dengue macaque model showing a higher predictability for vaccine efficacy in humans.

Validation of the Portuguese version of the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R) for the screening of binge eating disorder.

OBJECTIVE: The present paper describes the validation of the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R) designed for the diagnosis of binge eating disorder (BED) and sub-clinical binge eating. METHODS: 89 overweight women seeking treatment for binge eating and/or obesity were assessed with the Portuguese version of the Questionnaire of Eating and Weight Patterns and were, subsequently, interviewed with the eating disorders module of the Structured Clinical Interview for DSM-IV (SCID-I/P). Rates of binge eating disorder and sub-clinical cases of binge eating obtained with the Questionnaire on Eating and Weight Patterns-Revised were then compared to those obtained with the Structured Clinical Interview for DSM-IV. RESULTS: In the identification of binge eating, irrespective of the presence of all criteria for binge eating disorder the QEWP-R Questionnaire on Eating and Weight Patterns-Revised yielded a sensitivity value of 0.88, a specificity value of 0.63 and a positive predictive value of 0.825. Rates for the identification of the full syndrome of binge eating disorder were: sensitivity value of 0.548, a specificity value of 0.8 and a positive predictive value of 0.793. CONCLUSIONS: The Questionnaire on Eating and Weight Patterns-Revised can be useful in a first-step screening procedure to identify probable cases of binge eating. It can be useful as a screening tool and as a first step of clinical assessment of patients seeking treatment for binge eating and/or obesity.

Processar, elaborar, digerir: transtorno alimentar na contemporaneidade, leitura arquetípica / Process, elaborate, digest: eating disorder in the contemporary world, archetypal view / Procesar, elaborar, digerir: trastorno alimentario en la conteporaneidad, leitura arquetípica

O presente artigo propõe uma reflexão sobre a questão do feminino nos transtornos alimentares, correlacionando-os com a problemática da contemporaneidade. Inicialmente buscamos delimitar as características deste momento para depois ampliar nossa compreensão sobre como este contexto dialoga com a sintomatologia alimentar e o feminino arquetípico.

This article proposes a reflection on the question of the feminine in eating disorders, correlating with the complexity of contemporaneity. The authors initially set out the characteristics of this moment and then they expand the understanding of how this social context dialogues with eating symptomatology and with the feminine archetype.

El presente artículo propone una reflexión sobre la cuestión del femenino en los trastornos alimentarios, correlacionando con la problemática de la contemporaneidad. Inicialmente buscamos delimitar las características de este momento para luego ampliar nuestra comprensión sobre cómo este contexto dialoga con la sintomatología alimentaria y el femenino arquetípico.

Therapeutic effects of a horse riding simulator in children with cerebral palsy.

OBJECTIVE: To evaluate the efficacy of horse ridding simulator on the sitting postural control of children with spastic diplegia. METHOD: Forty children were randomly divided in a group using the simulator (RS) and a group performing conventional physical therapy (CT). FScan/Fmat equipment was used to register maximal displacement in antero-posterior (AP) and medio-lateral (ML) directions with children in sitting position. At the pre and post intervention stage both groups were classified according to the Gross Motor Function Classification System (GMFCS) and, after intervention, by the AUQEI questionnaire (Autoquestionnaire Qualité de vie Enfant Image). RESULTS: Comparison between groups disclosed statistically significant pos-intervention improvement both in the AP (p<0.0001) as in the ML (p<0.0069) direction in the RS group. CONCLUSION: The horse ridding simulator produced significant improvement in the postural control of children in sitting position, additionally showing a higher motor functionality and a better acceptance of the therapeutic intervention.

Study of the genetic stability of measles virus CAM-70 vaccine strain after serial passages in chicken embryo fibroblasts primary cultures.

To evaluate the genetic stability of the CAM-70 measles vaccine strain we have performed 10 serial passages of the seed lot virus FMS-7 in chicken embryo fibroblasts primary cultures (CEF) under production conditions. The nucleotide sequences of the seed lot virus, the virus from a vaccine vial (third passage) and from the 10th passage were determined and compared with each other and with sequences from other sources. The full genome analysis of the CAM-70 vaccine still considers it as the most divergent among all vaccine strains. The nucleotide sequence analyses of viral genomes from the three CAM-70 passage levels have demonstrated that they are identical. This study shows that the measles CAM-70 vaccine virus is highly adapted to its cultivation conditions and that its genetic stability contributes, in part, to the safety profile of the vaccine.

Accuracy and repeatability of a micro plaque reduction neutralization test for vaccinia antibodies.

The detection of neutralizing antibodies against vaccinia virus is a valuable tool for the investigation of previous smallpox vaccination. Compulsory smallpox vaccination ended in Brazil during the early 1970s, although the vaccine was available until the late 1970s. The threat of smallpox as a biological weapon has called the attention of public health authorities to the need for an evaluation of the immune status of the population. Based on our previous experience with a micro plaque reduction neutralization test (PRNT) for the evaluation of yellow fever immunity, a similar test was developed for the detection and quantification of vaccinia neutralizing antibodies. A cross-sectional study to test the repeatability and validity of plaque reduction neutralization test (PRNT) for vaccinia antibodies was performed in 182 subjects divided into two categories: subjects above 31 years old and the other > or = 35 years old. Cases were subjects considered to have been vaccinated with vaccinia virus if they declared vaccination history or evidenced vaccination marks. The assay is carried out in 96-well plates, provides results within 30 h, is easily performed, has good sensitivity (92.7%) and specificity (90.8), excellent repeatability (ICC 0.89 (0.88; 0.92)) and is thus suitable for use in mass screening of a population's antibody levels.

Therapeutic effects of a horse riding simulator in children with cerebral palsy / Efeitos terapêuticos de um simulador de equitação em crianças portadoras de paralisia cerebral

OBJECTIVE: To evaluate the efficacy of horse ridding simulator on the sitting postural control of children with spastic diplegia. METHOD: Forty children were randomly divided in a group using the simulator (RS) and a group performing conventional physical therapy (CT). FScan/Fmat equipment was used to register maximal displacement in antero-posterior (AP) and medio-lateral (ML) directions with children in sitting position. At the pre and post intervention stage both groups were classified according to the Gross Motor Function Classification System (GMFCS) and, after intervention, by the AUQEI questionnaire (Autoquestionnaire Qualité de vie Enfant Image). RESULTS: Comparison between groups disclosed statistically significant pos-intervention improvement both in the AP (p<0.0001) as in the ML (p<0.0069) direction in the RS group. CONCLUSION: The horse ridding simulator produced significant improvement in the postural control of children in sitting position, additionally showing a higher motor functionality and a better acceptance of the therapeutic intervention.

OBJETIVO: Avaliar os efeitos terapêuticos de um simulador de equitação no controle postural sentado de crianças portadoras de diplegia espástica. MÉTODO: Quarenta crianças foram aleatoriamente divididas em dois grupos: 20 utilizaram o simulador (GS) e 20 realizaram fisioterapia convencional (TC). Foi efetuado o registro dos deslocamentos máximos na direção ântero-posterior (AP) e médio-lateral (ML) com a criança sentada, utilizando-se o sistema FScan/Fmat. Antes e após intervenção as crianças foram classificadas pelo Gross Motor Function Classification System (GMFCS) e, após intervenção, pelo AUQEI (Autoquestionnaire Qualité de vie Enfant Image). RESULTADOS: Melhora estatisticamente significativa dos deslocamentos máximos foi observada após intervenção tanto na direção AP (p<0,0001) quanto na ML (p<0,0069) no grupo GS quando comparado ao grupo TC. CONCLUSÃO: O simulador de equitação produziu melhora significativamente maior no controle postural da criança sentada, aliada a maior funcionalidade motora e melhor aceitação da intervenção terapêutica.

Avaliação do pico de pressão e da frequência respiratória durante o uso de balão autoinflável por socorristas do Corpo de Bombeiros em um modelo de pulmão neonatal pré-termo / Evaluation of peak inspiratory pressure and respiratory rate during ventilation of a preterm infant lung model with a self-inflating bag by paramedics of the Fire Department

OBJETIVO: Avaliar o pico de pressão inspiratória e a frequência ventilatória obtidos por socorristas do Corpo de Bombeiros com a utilização de balão autoinflável em modelo de pulmão neonatal pré-termo. MÉTODOS: Estudo observacional descritivo incluindo 31 voluntários dentre 68 socorristas convidados, componentes de duas turmas do Programa de Capacitação Continuada do Corpo de Bombeiros. Durante três minutos, os socorristas ventilaram um simulador analógico de pulmão neonatal pré-termo, utilizando balão autoinflável de tamanho neonatal. Foram captados os picos de pressão inspiratória e a frequência respiratória por meio de um pneumotacógrafo e um monitor gráfico de ventilação. Os dados eram gravados e posteriormente analisados. RESULTADOS: A média do pico de pressão foi de 14,6±8,2cmH2O, sendo menor que 20 em 77,4 por cento das vezes, maior que 40 em 3,2 por cento das vezes, e entre 20 e 40cmH2O em 19,4 por cento das vezes. A média da frequência ventilatória foi de 38,3±10,3 ciclos por minuto, sendo menor que 40 em 51,6 por cento das vezes e entre 40 e 60 ciclos por minuto em 48,4 por cento das vezes; em nenhuma das vezes a pressão atingiu 60 ciclos por minuto. CONCLUSÕES: Os socorristas, na maioria das vezes, não atingiram o nível mínimo desejado de pressão de ventilação e frequência respiratória recomendados em protocolos internacionais durante a ventilação pulmonar neonatal com o balão autoinflável.

OBJECTIVE: To evaluate the peak inspiratory pressure and the ventilation rate obtained by paramedics of the Fire Department of Brasília, Brazil, when using a neonatal self-inflating bag on a preterm lung model. METHODS: Descriptive observational study including 31 volunteers, from 68 paramedics invited, who were components of two groups of the Fire Department's Continuous Training Program. For three minutes, the paramedics ventilated an analogical simulator of preterm infant lung using a neonatal self-inflating bag. The peak inspiratory pressure and the respiratory rate were captured by a pneumotachograph and a graphical monitor of ventilation. Data were recorded and analyzed. RESULTS: Mean peak pressures in cmH2O for test lung were 14.6±8.2, being less than 20 in 77.4 percent of the analyzed pressure curves, more than 40 in 3.2 percent, and between 20 and 40cmH2O in 19.4 percent of the curves. Mean ventilation rates were 38.3±10.3 cycles per minute, being less than 40 in 51.6 percent of the analyzed pressure curves, more than 60 in zero, and between 40 and 60 in 48.4 percent. In no occasion the pressure reached 60 cycles per minute. CONCLUSIONS: The paramedics, most of the time, did not achieve the advised minimum level of ventilation pressure and ventilation rates recommended by international guide lines during ventilation of a neonatal lung model with a self-inflating bag.

Validação da versão em português do Questionário sobre Padrões de Alimentação e Peso – Revisado (QEWP-R) para o rastreamento do transtorno da compulsão alimentar periódica / Validation of the portuguese version of the Questionnaire on Eating and Weight Patterns: revised (QEWP-R) for the screening of binge eating disorder

OBJECTIVE: The present paper describes the validation of the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R) designed for the diagnosis of binge eating disorder (BED) and sub-clinical binge eating. METHODS: 89 overweight women seeking treatment for binge eating and/or obesity were assessed with the Portuguese version of the Questionnaire of Eating and Weight Patterns and were, subsequently, interviewed with the eating disorders module of the Structured Clinical Interview for DSM-IV (SCID-I/P). Rates of binge eating disorder and sub-clinical cases of binge eating obtained with the Questionnaire on Eating and Weight Patterns-Revised were then compared to those obtained with the Structured Clinical Interview for DSM-IV. RESULTS: In the identification of binge eating, irrespective of the presence of all criteria for binge eating disorder the QEWP-R Questionnaire on Eating and Weight Patterns-Revised yielded a sensitivity value of 0.88, a specificity value of 0.63 and a positive predictive value of 0.825. Rates for the identification of the full syndrome of binge eating disorder were: sensitivity value of 0.548, a specificity value of 0.8 and a positive predictive value of 0.793. CONCLUSIONS: The Questionnaire on Eating and Weight Patterns-Revised can be useful in a first-step screening procedure to identify probable cases of binge eating. It can be useful as a screening tool and as a first step of clinical assessment of patients seeking treatment for binge eating and/or obesity.

OBJETIVO: O presente artigo descreve a validação do Questionário sobre Padrões de Alimentação e Peso-Revisado (QEWP-R), instrumento criado para o diagnóstico do transtorno da compulsão alimentar periódica (TCAP) e de quadros subclínicos de compulsão alimentar. MÉTODOS: A amostra foi composta por 89 mulheres em busca de tratamento especializado para compulsão alimentar e/ou obesidade, que preencheram o Questionário sobre Padrões de Alimentação e Peso-Revisado e, posteriormente, foram entrevistadas com o módulo para transtornos alimentares da Entrevista Clínica Estruturada para o DSM-IV (SCID-I/P). As taxas de transtorno da compulsão alimentar periódica e de diagnósticos subclínicos obtidas pelo Questionário sobre Padrões de Alimentação e Peso-Revisado foram comparadas às obtidas pela Entrevista Clínica Estruturada para o DSM-IV. RESULTADOS: Na identificação de compulsão alimentar (independente da presença de todos os elementos necessários para o diagnóstico de transtorno da compulsão alimentar periódica), a versão em português do Questionário sobre Padrões de Alimentação e Peso-Revisado apresentou sensibilidade de 0,88, especificidade de 0,63 e valor preditivo positivo de 0,825. Já para o diagnóstico de transtorno da compulsão alimentar periódica, o questionário apresentou sensibilidade = 0,548, especificidade = 0,8 e valor preditivo positivo de 0,793. CONCLUSÕES: O Questionário sobre Padrões de Alimentação e Peso-Revisado, em sua versão para o português, mostrou ser um instrumento útil na detecção de prováveis casos de compulsão alimentar. Pode ser utilizado como escala de rastreamento ou ainda como primeiro passo na avaliação clínica de pacientes que procuram tratamento para compulsão alimentar e/ou obesidade.

Critérios diagnósticos para os transtornos alimentares: conceitos em evolução / Diagnostic criteria for eating disorders: evolving concepts

O presente artigo apresenta o "estado de arte" da discussäo acerca dos critérios diagnósticos atuais dos transtornos alimentares: Anorexia Nervosa (AN), Bulimia Nervosa (BN) e Transtorno da Compulsäo Alimentar Periódica (TCAP). Dentre os aspectos controversos da AN, destacam-se: a concepçäo da distorçäo de imagem corporal, a necessidade da presença de amenorréia para o diagnóstico e a possibilidade de manifestaçäo de AN sem seu aspecto característico, o medo de engordar, em culturas näo ocidentalizadas. Quanto à BN, discute-se especialmente a concepçäo de compulsäo alimentar sua freqüência e duraçäo necessárias para o diagnóstico. O artigo apresenta também os critérios sugeridos para o diagnóstico de TCAP e comenta sua difícil distinçäo com a BN näo purgativa. As questöes aqui discutidas possibilitaräo o aprimoramento da nosologia da área

Biological characterization of clones derived from the Edmonstron strain of meales virus in comparison with Schwarz and CAM-70 vaccine strains

Four virus clones were derived from the Edmonston strain of measles virus by repeated plaque purification. These clones were compared with the vaccine strains Schwarz and CAM-70 in terms of biological activities including plaque formation, hemolysis and replication in Vero cells and chick embryo fibroblasts (CEF). Two clones of intermediate plaque yielded mixed plaque populations on subcultivation whereas the other two, showing small and large plaque sizes, showed stable plaque phenotypes. The vaccine strains showed consistent homogeneous plaque populations. All the Edmonston clones showed agglutinaton of monkey erythrocytes in isotonic solution while both vaccine strains hemagglutinated only in the presence of high salt concentrations. Variation in the hemolytic activity was observed among the four clones but no hemolytic activity was detected for the vaccine virus strains. Vaccine strains replicated efficiently both in Vero cells and CEF. All four clones showed efficient replication in Vero cells but different replication profiles in CEF. Two of them replicated efficiently, one was of intermediate efficiency and the other showed no replication in CEF. Two of the clones showed characteristics similar to vaccine strains. One in terms of size and homogeneity of plaques, the other for a low hemolytic activity and both for the efficiency of propagation in CEF.

Caracterização genômica e biológica do vírus do sarampo cepa vacinal CAM-70

Bio-Manguinhos possui a capacidade instalada de produção da vacina contra o sarampo utilizando a cepa viral Biken CAM-70. No momento, esta vacina não está sendo produzida devido à utilização, pelo Ministério da Saúde, da vacina tríplice viral (sarampo, caxumba e rubéola) nas campanhas de vacinação. Entretanto, o potencial de atender a mercados externos com uma vacina monovalente contra o sarampo, faz com que, a qualquer momento, a produção seja retomada. Neste contexto, a caracterização genômica e biológica deste vírus vacinal pode contribuir para a introdução de melhorias no processo de produção e nos fornecer dados para um maior conhecimento do nosso produto. Para avaliar a estabilidade genética da cepa CAM-70 foram realizadas dez passagens do vírus semente FMS-7 em culturas primárias de embrião de galinha ("chicken embryo fibroblast" = CEF). Os genomas do vírus semente FMS-7, do vírus proveniente do frasco de vacina (correspondente à 3ª passagem = VSF-3) e da 10ª passagem (VSF-10) foram seqüenciados e comparados entre si e com as seqüências disponíveis de vacinas de sarampo. O resultado do seqüenciamento nucleotídico direto de FMS-7, VSF-3 e VSF-10 revelou seqüências genômicas idênticas, demonstrando uma grande estabilidade genética deste vírus nas condições de cultivo empregadas. Neste trabalho investigamos também a influência do interferon (IFN) no rendimento viral. Culturas de CEF em alta densidade (AD) e baixa densidade (BD) celular foram inoculadas com CAM-70 e coletadas diariamente por um período de até 15 dias. As suspensões provenientes destas culturas foram tituladas em um teste para detecção de IFN e avaliados quanto à expressão da enzima 2-5 oligoadenilato sintetase (2-5OAS). O vírus CAM70 foi capaz de induzir a produção de IFN em CEF, como foi demonstrado através dos ensaios de titulação e pela expressão gênica de 2-5 OAS. A obtenção de títulos virais mais elevados em BD sugere que este vírus seja sensível ao IFN. O resultado obtido nos ensaios de IFN recomenda a produção da vacina em culturas em BD para o alcance de maiores rendimentos virais. Este estudo também demonstra que o vírus CAM-70 é altamente estável do ponto de vista genético, dentro dos parâmetros de produção. Esta estabilidade permite a extensão do uso dos lotes sementes de vacina e contribui para o perfil de segurança da vacina contra o sarampo confeccionada com o vírus CAM-70.