Cameron Bissett, Sandra Belij-Rammerstorfer, Marta Ulaszewska, Holly Smith, Reshma Kailath, Susan Morris, Claire Powers, Sarah Sebastian, Hannah R Sharpe, Elizabeth R Allen, Ziyin Wang, Robert F Cunliffe, Hadijatou J Sallah, Alexandra J Spencer, Sarah Gilbert, John S Tregoning, Teresa Lambe
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引用次数: 0
摘要
尽管流感病毒特许疫苗在减少病原体介导的疾病方面取得了成功,但它们在预防呼吸道病毒感染方面的效果较差,而且目前流感疫苗的季节性更新并不总是能成功地适应病毒漂移。大多数获得许可的流感疫苗和最近获得许可的 RSV 疫苗都是通过肌肉注射途径接种的。替代性免疫策略,如鼻内接种和 "原位牵引 "疗法,可提供更有效的呼吸道病毒灭菌保护。我们设计、开发并在临床前动物模型中测试了一种基于 ChAdOx1 的双价疫苗(ChAdOx1-NP + M1-RSVF),该疫苗编码了甲型流感病毒的保守核蛋白和基质 1 蛋白以及改良的预融合稳定 RSV A F 蛋白。其目的是在呼吸道粘膜和全身诱导针对异型流感病毒的广泛、交叉保护性组织驻留 T 细胞和针对 RSV 的中和抗体。通过肌肉注射原体-鼻内增强(IM-IN)方案给小鼠注射后,小鼠在面对甲型 RSV、甲型 H3N2 流感或 H1N1 流感挑战时都能获得超强的保护。这些结果为进一步临床开发以原浆-注射方案接种的流感和 RSV 泛型疫苗提供了支持。
Systemic prime mucosal boost significantly increases protective efficacy of bivalent RSV influenza viral vectored vaccine.
Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and "prime-pull" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.
NPJ VaccinesImmunology and Microbiology-Immunology
CiteScore
11.90
自引率
4.30%
发文量
146
审稿时长
11 weeks
期刊介绍:
Online-only and open access, npj Vaccines is dedicated to highlighting the most important scientific advances in vaccine research and development.