Camacho Luiz Antonio Bastos, Freire Marcos da Silva, Leal Maria da Luz Fernandes, Aguiar Savitri Gomes de, Nascimento Jussara Pereira do, Iguchi Takumi, Lozana José de Azevedo, Farias Roberto Henrique Guedes
Escola Nacional de Saúde Pública, Fundação Oswaldo Cruz (Fiocruz), Rio de Janeiro, RJ, Brazil.
Rev Saude Publica. 2004 Oct;38(5):671-8. doi: 10.1590/s0034-89102004000500009. Epub 2004 Oct 18.
To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots).
An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind). Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than 0.67.
Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7.
The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.
比较来自世界卫生组织-17D和巴西17DD亚株（不同种子批）的三种黄热病疫苗的免疫原性。
在里约热内卢对1087名成年人进行了一项等效性试验。按照标准化程序接种由巴西里约热内卢的菲奥克鲁兹生物医学研究所生产的疫苗，该程序经过调整以允许将参与者随机分入编码疫苗类型组（双盲）。比较免疫前后血清样本中的黄热病中和抗体滴度。等效性定义为血清转化率差异不超过5个百分点，几何平均滴度（GMT）之比高于0.67。
先前血清学阴性的受试者血清转化率为98%或更高，包括先前血清学阳性者在内的全部疫苗接种者队列中90%或更多的人血清转化率为98%或更高。血清转化率差异范围为-0.05%至-3.02%。各疫苗的免疫反应强度也非常相似：14.5至18.6 IU/mL。GMT之比范围为0.78至0.93。将安慰剂组考虑在内，疫苗可解释93%的血清转化情况。在接种疫苗的受试者中，第3天至第7天有2.7%检测到病毒血症。
在安慰剂对照双盲随机试验中首次证明了17D和17DD亚株黄热病疫苗具有等效免疫原性。该研究完成了一种新疫苗种子批的临床验证过程，为一家主要生产商在疫苗生产中使用替代减毒株提供了证据，并为17DD疫苗在其他国家的使用提供了证据。
