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在非流行地区的一组成人和儿童中,单剂量17DD黄热病疫苗的免疫原性及其与登革热和寨卡病毒血清阳性的关联。

Immunogenicity of a single dose of the 17DD yellow fever vaccine in a cohort of adults and children in a non-endemic area, and its association with dengue and Zika seropositivity.

作者信息

Saucha Camylla Veloso Valença, Maia Maria de Lourdes de Sousa, Sousa Eduardo Sérgio Soares, de Oliveira Patrícia Mouta Nunes, Xavier Janaína Reis, de Castro Thalita da Matta, Cruz Robson Leite de Souza, Schwarcz Waleska Dias, Pereira Renata Carvalho, Azevedo Adriana de Souza, de Filippis Ana Maria Bispo, Ferroco Clara Lucy de Vasconcellos, Pizzini Geovanna de Lima Cunha, Brum Ricardo Cristiano de Souza, Secundino Leonardo, Andrade Maria de Fátima de Sousa, de Oliveira Raquel de Vasconcellos Carvalhaes, Simões Marisol, Cerbino-Neto José, Martins-Filho Olindo Assis, Campi-Azevedo Ana Carolina, de Lima Sheila Maria Barbosa, Camacho Luiz Antonio Bastos

机构信息

Departamento de Epidemiologia, Escola Nacional de Saúde Pública Sergio Arouca (ENSP), Fiocruz, Rio de Janeiro-RJ, Brasil.

Departamento de Assuntos Médicos, Estudos Clínicos e Vigilância Pós-Registro (DEAME), Bio-Manguinhos: Instituto de Tecnologia em Imunobiológicos, Fiocruz, Rio de Janeiro-RJ, Brasil.

出版信息

PLoS Negl Trop Dis. 2025 Apr 9;19(4):e0012993. doi: 10.1371/journal.pntd.0012993. eCollection 2025 Apr.

Abstract

In 2013, the World Health Organization (WHO) withdrew the recommendation of booster doses of the yellow fever (YF) vaccine, based on retrospective and cross-sectional studies that showed lifelong protective immunity from a single dose. Currently, yellow fever transmission in Brazil occurs only through the jungle (sylvatic) cycle. However, the high vector density of Aedes aegypti, which transmits other orthoflaviviruses, is a concern for the expansion of YF in other regions of the country. We conducted a cohort study to assess the duration of vaccine-induced immunity in adults and children residing in an area without wild-type YF virus circulation but with a high incidence of other orthoflaviviruses. This phase IV, uncontrolled cohort study was conducted in three municipalities in northeastern Brazil. The 17DD strain vaccine was administered to children aged 9 months to 4 years and adults aged 18 to 50 years. Blood samples for antibody titration were collected before vaccination, 30-45 days after, and one year after vaccination. The following assays were used: µFRNT for yellow fever and dengue; PRNT for Zika; and chemiluminescence for Zika (IgG and IgM) and dengue (IgG). YF seroconversion rates 30-45 days post-vaccination increased with age, reaching 99% in adults, while 10% of infants remained without detectable antibodies. Seropositivity for dengue neutralizing antibodies was inversely associated with YF antibody titers 30-45 days post-vaccination. Previous Zika infection showed no substantial association with YF antibody titers post-vaccination. One year after vaccination, a considerable reduction in YF antibody titers was observed across all age groups, regardless of prior dengue or Zika infections. Our data support the Brazilian National Immunization Program's recommendation for a booster dose of the vaccine at 4 years of age. Current recommendations assuming lifelong protection from a single dose of the YF vaccine do not appear to provide sufficient protection in high-risk areas, particularly where infants are the primary target for vaccination.

摘要

2013年,世界卫生组织(WHO)基于回顾性和横断面研究撤回了黄热病(YF)疫苗加强剂量的建议,这些研究表明单剂量疫苗可提供终身保护性免疫。目前,巴西的黄热病传播仅通过丛林(野生)循环发生。然而,传播其他正黄病毒的埃及伊蚊的高媒介密度,是该国其他地区黄热病传播扩大的一个担忧因素。我们进行了一项队列研究,以评估居住在无野生型黄热病病毒传播但其他正黄病毒发病率高的地区的成人和儿童中疫苗诱导免疫的持续时间。这项IV期非对照队列研究在巴西东北部的三个市进行。对9个月至4岁的儿童和18至50岁的成人接种17DD株疫苗。在接种疫苗前、接种后30 - 45天和接种后一年采集用于抗体滴定的血样。使用了以下检测方法:用于黄热病和登革热的微量荧光中和试验(µFRNT);用于寨卡病毒的蚀斑减少中和试验(PRNT);以及用于寨卡病毒(IgG和IgM)和登革热(IgG)的化学发光法。接种疫苗后30 - 45天的黄热病血清转化率随年龄增加,成人中达到99%,而10%的婴儿仍未检测到抗体。接种疫苗后30 - 45天,登革热中和抗体的血清阳性率与黄热病抗体滴度呈负相关。既往寨卡病毒感染与接种疫苗后的黄热病抗体滴度无实质性关联。接种疫苗一年后,所有年龄组的黄热病抗体滴度均显著降低,无论既往是否感染登革热或寨卡病毒。我们的数据支持巴西国家免疫规划关于4岁时接种一剂疫苗加强针的建议。目前假设单剂量黄热病疫苗可提供终身保护的建议,在高风险地区似乎无法提供足够的保护,特别是在婴儿是主要接种对象的地区。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cd9a/12047785/83373d22da46/pntd.0012993.g001.jpg

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