Barreiro Antonio, Prenafeta Antoni, Bech-Sabat Gregori, Roca Mercè, Perozo Mur Eva, March Ricard, González-González Luis, Madrenas Laia, Corominas Júlia, Fernández Alex, Moros Alexandra, Cañete Manuel, Molas Mercè, Pentinat-Pelegrin Thais, Panosa Clara, Moreno Alberto, Puigvert Molas Ester, Pol Vilarrassa Eva, Palmada Jordi, Garriga Carme, Prat Cabañas Teresa, Iglesias-Fernández Javier, Vergara-Alert Júlia, Lorca-Oró Cristina, Roca Núria, Fernández-Bastit Leira, Rodon Jordi, Pérez Mònica, Segalés Joaquim, Pradenas Edwards, Marfil Silvia, Trinité Benjamin, Ortiz Raquel, Clotet Bonaventura, Blanco Julià, Díaz Pedroza Jorge, Ampudia Carrasco Rosa, Rosales Salgado Yaiza, Loubat-Casanovas Jordina, Capdevila Larripa Sara, Prado Julia Garcia, Barretina Jordi, Sisteré-Oró Marta, Cebollada Rica Paula, Meyerhans Andreas, Ferrer Laura
HIPRA, Avda. La Selva, 135, Amer, 17170 Girona, Spain.
Nostrum Biodiscovery, Avenue de Josep Tarradellas, 8-10, 3-2, 08029 Barcelona, Spain.
iScience. 2023 Mar 17;26(3):106126. doi: 10.1016/j.isci.2023.106126. Epub 2023 Feb 2.
Current COVID-19 vaccines have been associated with a decline in infection rates, prevention of severe disease, and a decrease in mortality rates. However, SARS-CoV-2 variants are continuously evolving, and development of new accessible COVID-19 vaccines is essential to mitigate the pandemic. Here, we present data on preclinical studies in mice of a receptor-binding domain (RBD)-based recombinant protein vaccine (PHH-1V) consisting of an RBD fusion heterodimer comprising the B.1.351 and B.1.1.7 SARS-CoV-2 variants formulated in SQBA adjuvant, an oil-in-water emulsion. A prime-boost immunisation with PHH-1V in BALB/c and K18-hACE2 mice induced a CD4 and CD8 T cell response and RBD-binding antibodies with neutralizing activity against several variants, and also showed a good tolerability profile. Significantly, RBD fusion heterodimer vaccination conferred 100% efficacy, preventing mortality in SARS-CoV-2 infected K18-hACE2 mice, but also reducing Beta, Delta and Omicron infection in lower respiratory airways. These findings demonstrate the feasibility of this recombinant vaccine strategy.
目前的新冠疫苗与感染率下降、预防重症疾病以及死亡率降低有关。然而，新冠病毒变种在不断演变，开发新的可及性新冠疫苗对于缓解疫情至关重要。在此，我们展示了一种基于受体结合域（RBD）的重组蛋白疫苗（PHH-1V）在小鼠临床前研究的数据，该疫苗由包含B.1.351和B.1.1.7新冠病毒变种的RBD融合异二聚体组成，配方为水包油乳剂SQBA佐剂。在BALB/c和K18-hACE2小鼠中用PHH-1V进行初免-加强免疫诱导了CD4和CD8 T细胞反应以及具有针对多种变种的中和活性的RBD结合抗体，并且还显示出良好的耐受性。值得注意的是，RBD融合异二聚体疫苗接种具有100%的效力，可预防新冠病毒感染的K18-hACE2小鼠死亡，还能减少下呼吸道中的贝塔、德尔塔和奥密克戎感染。这些发现证明了这种重组疫苗策略的可行性。
