Fougeroux Cyrielle, Hagen Sven Hendrik, Goksøyr Louise, Aves Kara-Lee, Okholm Anna Kathrine, Morin Candice, Lokras Abhijeet Girish, Baghel Saahil Sandeep, Foged Camilla, van de Vegte-Bolmer Marga, van Gemert Geert-Jan, Jore Matthijs M, Vidal-Calvo Elena Ethel, Gustavsson Tobias, Salanti Ali, Theander Thor Grundtvig, Nielsen Morten Agertoug, de Jongh Willem Adriaan, Sander Bertelsen Adam Frederik
AdaptVac Aps, Copenhagen, Denmark.
Centre for Translational Medicine and Parasitology, Department for Immunology and Microbiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Nat Nanotechnol. 2025 May 14. doi: 10.1038/s41565-025-01889-1.
The COVID-19 pandemic has emphasized the potential of mRNA vaccines in fighting pandemics, owing to their rapid development, strong immunogenicity and adaptability. However, a drawback is their dose-limiting reactogenicity and inability to generate durable humoral immunity. Here we introduce a modular nucleotide vaccine platform combining the advantages of genetic and capsid virus-like-particle-based vaccines. This platform allows for the display of various antigens on different capsid virus-like particles, improving the magnitude, quality and longevity of the vaccine-induced immune responses. We applied this technology to enhance the immunogenicity of the Pfs25 antigen. Immunization with lipid-nanoparticle-formulated mRNA encoding Pfs25 capsid virus-like particles resulted in higher and potentially more durable anti-Pfs25 antibody responses, along with enhanced functional activity, compared with an mRNA vaccine encoding soluble Pfs25. By improving both humoral and cellular immune responses, this approach may reduce the dose and number of administrations required for effective protection. As a result, it can improve the feasibility of both DNA- and mRNA-based vaccines targeting pandemic and endemic infectious diseases.
2019冠状病毒病（COVID-19）大流行凸显了信使核糖核酸（mRNA）疫苗在抗击大流行方面的潜力，这得益于其研发速度快、免疫原性强和适应性强。然而，一个缺点是其剂量限制性反应原性以及无法产生持久的体液免疫。在此，我们介绍一种模块化核苷酸疫苗平台，该平台结合了基于基因和衣壳病毒样颗粒疫苗的优点。该平台允许在不同的衣壳病毒样颗粒上展示各种抗原，从而提高疫苗诱导的免疫反应的强度、质量和持久性。我们应用这项技术来增强Pfs25抗原的免疫原性。与编码可溶性Pfs25的mRNA疫苗相比，用脂质纳米颗粒配制的编码Pfs25衣壳病毒样颗粒的mRNA进行免疫，可产生更高且可能更持久的抗Pfs25抗体反应，同时增强功能活性。通过改善体液免疫和细胞免疫反应，这种方法可能会减少有效保护所需的剂量和给药次数。因此，它可以提高针对大流行和地方性传染病的基于DNA和mRNA的疫苗的可行性。
