BACKGROUND A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. RESULTS A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition antibody responses to a standard-dose TIV, and TIV did not impact the immune response to the RSV F vaccine. CONCLUSIONS RSV F protein nanoparticle vaccine induced increases in measures of functional immunity to RSV in older adults and demonstrated an acceptable safety profile. Adjuvanted formulations provided additional immunogenicity benefit as compared to increasing antigen dose alone. This trial was registered with ClinicalTrials.gov number NCT01709019.

中文翻译：

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老年人呼吸道合胞病毒融合蛋白（RSV F）纳米颗粒疫苗的免疫原性和安全性。

背景技术呼吸道合胞病毒（RSV）感染的预防策略构成了老年人中未被充分认识的未满足的医疗需求。在此评估了在成人受试者中与许可的灭活三价流感疫苗（TIV）同时施用的四种新型重组RSV F纳米颗粒疫苗（60或90μgRSV F蛋白，有或没有磷酸铝佐剂）的制剂的安全性和免疫原性随机，观察者盲的研究。结果共有220名年龄在60岁以上，无症状性心肺疾病的健康男性和女性同时接受TIV和RSV F疫苗或安慰剂的疫苗接种。所有疫苗制剂均产生可接受的安全性，没有疫苗相关的严重不良事件或全身毒性的证据。疫苗诱导的免疫反应迅速，最早在接种疫苗后7天就升高；并且在所有制剂上在数量上是可比的，在疫苗接种后28（无佐剂）或56（佐剂）日内达到最大水平。抗F蛋白IgG抗体的峰值水平上升了3.6到5.6倍，在60μg剂量下观察到了佐剂作用，在无佐剂60和90μg方案下观察到了剂量效应。疫苗接种后12个月，抗F反应持续存在。在第0天时，帕利珠单抗竞争性抗体低于可量化的水平（<33μg/ mL）。对Site II肽具有特异性的抗体的上升以及帕利珠单抗竞争性结合活性，表示抗体在抗原性位点或附近与抗原性位点结合II对F蛋白的反应与抗F反应密切相关。然而，在佐剂疫苗接受者中，较高比例的抗体以高亲和力与Site II肽结合。在所有受试者中，第0天的中和抗体都很高，并且在接种疫苗后上升了1.3到1.7倍。重要的是，与TIV共同使用的RSV F疫苗不会影响血清对标准剂量TIV的血凝抑制抗体的反应，并且TIV不会影响对RSV F疫苗的免疫反应。结论RSV F蛋白纳米颗粒疫苗诱导了老年人对RSV的功能性免疫增强，并显示出可接受的安全性。与单独增加抗原剂量相比，佐剂制剂提供了额外的免疫原性益处。该试验已在ClinicalTrials.gov上注册，编号为NCT01709019。