Riffault Sabine, Hägglund Sara, Guzman Efrain, Näslund Katarina, Jouneau Luc, Dubuquoy Catherine, Pietralunga Vincent, Laubreton Daphné, Boulesteix Olivier, Gauthier David, Remot Aude, Boukaridi Abdelhak, Falk Alexander, Shevchenko Ganna, Lind Sara Bergström, Vargmar Karin, Zhang Baoshan, Kwong Peter D, Rodriguez María Jose, Duran Marga Garcia, Schwartz-Cornil Isabelle, Eléouët Jean-François, Taylor Geraldine, Valarcher Jean François
University Paris-Saclay, INRAE, UVSQ, VIM, 78350 Jouy-en-Josas, France.
Host Pathogen Interaction Group, Department of Clinical Sciences, Swedish University of Agricultural Sciences, 875007 Uppsala, Sweden.
Vaccines (Basel). 2020 May 18;8(2):231. doi: 10.3390/vaccines8020231.
Achieving safe and protective vaccination against respiratory syncytial virus (RSV) in infants and in calves has proven a challenging task. The design of recombinant antigens with a conformation close to their native form in virus particles is a major breakthrough. We compared two subunit vaccines, the bovine RSV (BRSV) pre-fusion F (preF) alone or with nanorings formed by the RSV nucleoprotein (preF+N). PreF and N proteins are potent antigenic targets for neutralizing antibodies and T cell responses, respectively. To tackle the challenges of neonatal immunization, three groups of six one-month-old calves with maternally derived serum antibodies (MDA) to BRSV received a single intramuscular injection of PreF, preF+N with Montanide ISA61 VG (ISA61) as adjuvant or only ISA61 (control). One month later, all calves were challenged with BRSV and monitored for virus replication in the upper respiratory tract and for clinical signs of disease over one week, and then post-mortem examinations of their lungs were performed. Both preF and preF+N vaccines afforded safe, clinical, and virological protection against BRSV, with little difference between the two subunit vaccines. Analysis of immune parameters pointed to neutralizing antibodies and antibodies to preF as being significant correlates of protection. Thus, a single shot vaccination with preF appears sufficient to reduce the burden of BRSV disease in calves with MDA.
事实证明，要实现对婴儿和小牛的呼吸道合胞病毒（RSV）进行安全有效的疫苗接种是一项具有挑战性的任务。设计构象接近病毒颗粒中天然形式的重组抗原是一项重大突破。我们比较了两种亚单位疫苗，即单独的牛RSV（BRSV）融合前F蛋白（preF）或与由RSV核蛋白形成的纳米环（preF+N）。PreF和N蛋白分别是中和抗体和T细胞反应的有效抗原靶点。为应对新生儿免疫的挑战，三组六头带有母源血清抗体（MDA）的BRSV的1月龄小牛分别接受了一次肌肉注射PreF、以Montanide ISA61 VG（ISA61）作为佐剂的preF+N或仅注射ISA61（对照组）。一个月后，所有小牛均受到BRSV攻击，并在一周内监测其上呼吸道中的病毒复制及疾病的临床症状，然后对其肺部进行尸检。PreF和preF+N疫苗均提供了针对BRSV的安全、临床和病毒学保护，两种亚单位疫苗之间差异不大。免疫参数分析表明，中和抗体和针对preF的抗体是保护的重要相关因素。因此，单次注射preF似乎足以减轻带有MDA的小牛的BRSV疾病负担。
