RT Journal Article
SR Electronic
T1 A Versatile Platform to Incorporate Viral Trimeric Antigens into Self-Assembling Nanoparticle Immunogens
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.06.11.147496
DO 10.1101/2020.06.11.147496
A1 Baoshan Zhang
A1 Cara W. Chao
A1 Yaroslav Tsybovsky
A1 Adam S. Olia
A1 Guillaume Stewart-Jones
A1 Raffaello Verardi
A1 Shuishu Wang
A1 Tongqing Zhou
A1 Peter D. Kwong
YR 2020
UL http://biorxiv.org/content/early/2020/06/12/2020.06.11.147496.abstract
AB Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens may be complicated by inefficiencies in their production, especially with the metastable glycosylated trimeric type 1 fusion machines that are prevalent viral vaccine targets. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N-linked glycan was added to the nanoparticle surface. Respiratory syncytial virus fusion (F) glycoprotein trimer – stabilized in the prefusion conformation by multiple disulfides and fused with SpyCatcher – could be efficiently conjugated to LuS-SpyTag or to ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric antigens from viral respiratory pathogens, including the recently identified SARS-CoV-2.Competing Interest StatementThe authors have declared no competing interest.