Cajaraville Ana Carolina Dos Reis Albuquerque, Gomes Mariana Pierre de Barros, Azamor Tamiris, Pereira Renata Carvalho, Neves Patrícia Cristina da Costa, De Luca Paula Mello, Lima Sheila Maria Barbosa de, Gaspar Luciane Pinto, Caride Elena, Freire Marcos da Silva, Medeiros Marco Alberto
Vice Diretoria de Desenvolvimento Tecnológico (VDTEC), Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), FIOCRUZ Av. Brasil, Rio de Janeiro 21040-900, Brazil.
Instituto Oswaldo Cruz (IOC), FIOCRUZ Av. Brasil, Rio de Janeiro 21040-900, Brazil.
Vaccines (Basel). 2022 Dec 28;11(1):73. doi: 10.3390/vaccines11010073.
The attenuated yellow fever (YF) vaccine is one of the most successful vaccines ever developed. After a single dose administration YF vaccine can induce balanced Th1/Th2 immune responses and long-lasting neutralizing antibodies. These attributes endorsed it as a model of how to properly stimulate the innate response to target protective immune responses. Despite their longstanding success, attenuated YF vaccines can cause rare fatal adverse events and are contraindicated for persons with immunosuppression, egg allergy and age < 6 months and >60 years. These drawbacks have encouraged the development of a non-live vaccine. The aim of the present study is to characterize and compare the immunological profile of two adjuvant formulations of an inactivated YF 17DD vaccine candidate. Inactivated YF vaccine formulations based on alum (Al(OH)3) or squalene (AddaVax®) were investigated by immunization of C57BL/6 mice in 3-dose or 2-dose schedules, respectively, and compared with a single dose of attenuated YF virus 17DD. Sera were analyzed by ELISA and Plaque Reduction Neutralization Test (PRNT) for detection of total IgG and neutralizing antibodies against YF virus. In addition, splenocytes were collected to evaluate cellular responses by ELISpot. Both inactivated formulations were able to induce high titers of IgG against YF, although neutralizing antibodies levels were borderline on pre-challenge samples. Analysis of IgG subtypes revealed a predominance of IgG2a associated with improved neutralizing capacity in animals immunized with the attenuated YF vaccine, and a predominance of IgG1 in groups immunized with experimental non-live formulations (alum and AddaVax®). After intracerebral (IC) challenge, attenuated and inactivated vaccine formulations showed an increase in neutralizing antibodies. The AddaVax®-based inactivated vaccine and the attenuated vaccine achieved 100% protection, and alum-based equivalent formulation achieved 70% protection.
减毒黄热病（YF）疫苗是有史以来最成功的疫苗之一。单剂量接种YF疫苗可诱导平衡的Th1/Th2免疫反应和持久的中和抗体。这些特性使其成为如何正确刺激先天反应以靶向保护性免疫反应的典范。尽管减毒YF疫苗长期以来取得了成功，但仍可导致罕见的致命不良事件，并且免疫功能低下、对鸡蛋过敏以及年龄小于6个月和大于60岁的人群禁用。这些缺点促使人们研发非活疫苗。本研究的目的是表征和比较一种灭活YF 17DD候选疫苗的两种佐剂配方的免疫谱。分别通过按3剂或2剂方案免疫C57BL/6小鼠，研究了基于明矾（Al(OH)3）或角鲨烯（AddaVax®）的灭活YF疫苗配方，并与单剂量减毒YF病毒17DD进行比较。通过ELISA和蚀斑减少中和试验（PRNT）分析血清，以检测针对YF病毒的总IgG和中和抗体。此外，收集脾细胞通过ELISpot评估细胞反应。两种灭活配方均能够诱导高滴度的抗YF IgG，尽管在攻毒前样本中中和抗体水平处于临界值。IgG亚型分析显示，在用减毒YF疫苗免疫的动物中，与中和能力改善相关的IgG2a占主导，而在用实验性非活配方（明矾和AddaVax®）免疫的组中，IgG1占主导。脑内（IC）攻毒后，减毒和灭活疫苗配方的中和抗体均有所增加。基于AddaVax®的灭活疫苗和减毒疫苗实现了100%的保护，而基于明矾的等效配方实现了70%的保护。
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