Adenovectors encoding RSV-F protein induce durable and mucosal immunity in macaques after two intramuscular administrations.,npj Vaccines

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Adenovectors encoding RSV-F protein induce durable and mucosal immunity in macaques after two intramuscular administrations.
npj Vaccines ( IF 6.9 ) Pub Date : 2019-12-20 , DOI: 10.1038/s41541-019-0150-4
N C Salisch ₁ , A Izquierdo Gil ₁ , D N Czapska-Casey ₁ , L Vorthoren _{1,

2} , J Serroyen ₃ , J Tolboom ₃ , E Saeland ₁ , H Schuitemaker ₁ , R C Zahn ₁

Affiliation

Respiratory Syncytial Virus (RSV) can cause severe respiratory disease, yet a licensed vaccine is not available. We determined the immunogenicity of two homologous and one heterologous intramuscular prime-boost vaccination regimens using replication-incompetent adenoviral vectors of human serotype 26 and 35 (Ad26 and Ad35), expressing a prototype antigen based on the wild-type fusion (F) protein of RSV strain A2 in adult, RSV-naive cynomolgus macaques. All regimens induced substantial, boostable antibody responses that recognized the F protein in pre- and postfusion conformation, neutralized multiple strains of RSV, and persisted for at least 80 weeks. Vaccination induced durable systemic RSV-F-specific T-cell responses characterized mainly by CD4+ T cells expressing Th1-type cytokines, as well as RSV-F-specific CD4+ and CD8+ T cells, IgG, and IgA in the respiratory tract. Intramuscular immunization with Ad26 and 35 vectors thus is a promising approach for the development of an optimized RSV vaccine expected to induce long-lasting humoral and cellular immune responses that distribute systemically and to mucosal sites.

中文翻译：

两次肌肉注射后，编码RSV-F蛋白的腺载体在猕猴中诱导持久的和粘膜免疫。

呼吸道合胞病毒（RSV）可能导致严重的呼吸道疾病，但尚无许可的疫苗。我们使用人血清型26和35（Ad26和Ad35）的无复制能力的腺病毒载体确定了两种同源和一种异源肌肉内初免-加强免疫接种方案的免疫原性，这些载体表达基于野生型融合蛋白（F）的原型抗原成年RSV幼食猕猴猕猴中的RSV毒株A2。所有方案均诱导了实质性的，可加强的抗体反应，该反应识别融合前和融合后构象中的F蛋白，中和了多个RSV毒株，并持续了至少80周。疫苗接种可诱导持久的全身性RSV-F特异性T细胞应答，其主要特征是表达Th1型细胞因子的CD4 + T细胞以及RSV-F特异性CD4 +和CD8 + T细胞，IgG，和呼吸道中的IgA。因此，用Ad26和35种载体进行肌内免疫是开发优化的RSV疫苗的有前途的方法，所述RSV疫苗有望诱导持久的体液和细胞免疫应答，全身和分布于粘膜部位。

更新日期：2019-12-20

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