Norizwan Jaffar Ali Muhamad, Tan Wen Siang
Department of Microbiology, Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia.
Curr Res Microb Sci. 2024 Nov 15;8:100317. doi: 10.1016/j.crmicr.2024.100317. eCollection 2025.
The threat of influenza A virus (IAV) remains an annual health concern, as almost 500,000 people die each year due to the seasonal flu. Current flu vaccines are highly dependent on embryonated chicken eggs for production, which is time consuming and costly. These vaccines only confer moderate protections in elderly people, and they lack cross-protectivity; thereby requiring annual reformulation to ensure effectiveness against contemporary circulating strains. To address current limitations, new strategies are being sought, with great emphasis given on exploiting IAV's conserved antigens for vaccine development, and by using different vaccine technologies to enhance immunogenicity and expedite vaccine production. Among these technologies, there are growing pre-clinical and clinical studies involving virus-like particles (VLPs), as they are capable to display multiple conserved IAV antigens and augment their immune responses. In this review, we outline recent findings involving broadly effective IAV antigens and strategies to display these antigens on VLPs. Current production systems for IAV VLP vaccines are comprehensively reviewed. Pain-free methods for administration of IAV VLP vaccines through intranasal and transdermal routes, as well as the mechanisms in stimulating immune responses are discussed in detail. The future perspectives of VLPs in IAV vaccine development are discussed, particularly concerning their potentials in overcoming current immunological limitations of IAV vaccines, and their inherent advantages in exploring intranasal vaccination studies. We also propose avenues to expedite VLP vaccine production, as we envision that there will be more clinical trials involving IAV VLP vaccines, leading to commercialization of these vaccines in the near future.
甲型流感病毒（IAV）的威胁仍然是每年的健康关注点，因为每年有近50万人死于季节性流感。目前的流感疫苗在生产上高度依赖鸡胚，这既耗时又昂贵。这些疫苗在老年人中仅提供中等程度的保护，而且缺乏交叉保护；因此需要每年重新配方以确保对当代流行毒株有效。为了解决当前的局限性，人们正在寻找新的策略，重点是利用IAV的保守抗原进行疫苗开发，并使用不同的疫苗技术来增强免疫原性和加快疫苗生产。在这些技术中，涉及病毒样颗粒（VLP）的临床前和临床研究越来越多，因为它们能够展示多种保守的IAV抗原并增强免疫反应。在这篇综述中，我们概述了涉及广泛有效的IAV抗原的最新发现以及在VLP上展示这些抗原的策略。对目前IAV VLP疫苗的生产系统进行了全面综述。详细讨论了通过鼻内和经皮途径接种IAV VLP疫苗的无痛方法以及刺激免疫反应的机制。讨论了VLP在IAV疫苗开发中的未来前景，特别是关于它们在克服IAV疫苗当前免疫局限性方面的潜力以及它们在探索鼻内疫苗接种研究中的固有优势。我们还提出了加快VLP疫苗生产的途径，因为我们预计未来会有更多涉及IAV VLP疫苗的临床试验，并在不久的将来实现这些疫苗的商业化。
