Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in cattle pre-exposed to bovine RSV.,Nature Communications

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Pre-fusion RSV F strongly boosts pre-fusion specific neutralizing responses in cattle pre-exposed to bovine RSV.
Nature Communications ( IF 14.7 ) Pub Date : 2017-10-20 , DOI: 10.1038/s41467-017-01092-4
Ann-Muriel Steff ₁ , James Monroe _{1,

2} , Kristian Friedrich ₁ , Sumana Chandramouli ₁ , Thi Lien-Anh Nguyen ₃ , Sai Tian ₁ , Sarah Vandepaer ₄ , Jean-François Toussaint ₃ , Andrea Carfi _{1,

5}

Affiliation

Human respiratory syncytial virus (hRSV) is responsible for serious lower respiratory tract disease in infants and in older adults, and remains an important vaccine need. RSV fusion (F) glycoprotein is a key target for neutralizing antibodies. RSV F stabilized in its pre-fusion conformation (DS-Cav1 F) induces high neutralizing antibody titers in naïve animals, but it remains unknown to what extent pre-fusion F can boost pre-existing neutralizing responses in RSV seropositive adults. We here assess DS-Cav1 F immunogenicity in seropositive cattle pre-exposed to bovine RSV, a virus closely related to hRSV. A single immunization with non-adjuvanted DS-Cav1 F strongly boosts RSV neutralizing responses, directed towards pre-fusion F-specific epitopes, whereas a post-fusion F is unable to do so. Vaccination with pre-fusion F thus represents a promising strategy for maternal immunization and for other RSV vaccine target populations such as older adults.

中文翻译：

融合前 RSV F 强烈增强预先暴露于牛 RSV 的牛的融合前特异性中和反应。

人类呼吸道合胞病毒 (hRSV) 会导致婴儿和老年人的严重下呼吸道疾病，并且仍然是一种重要的疫苗需求。 RSV 融合 (F) 糖蛋白是中和抗体的关键靶点。稳定在其融合前构象的 RSV F (DS-Cav1 F) 可在幼稚动物中诱导高中和抗体滴度，但目前尚不清楚融合前 F 能在多大程度上增强 RSV 血清阳性成人中预先存在的中和反应。我们在此评估了预先暴露于牛 RSV（一种与 hRSV 密切相关的病毒）的血清阳性牛的 DS-Cav1 F 免疫原性。使用非佐剂 DS-Cav1 F 进行单次免疫可强烈增强针对融合前 F 特异性表位的 RSV 中和反应，而融合后 F 则无法做到这一点。因此，融合前 F 疫苗接种代表了孕产妇免疫和其他 RSV 疫苗目标人群（例如老年人）的一种有前途的策略。

更新日期：2017-10-20

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