2024-03-12 ペンシルベニア州立大学(PennState)
<関連情報>
- https://www.psu.edu/news/eberly-college-science/story/new-nasal-vaccine-platform-helps-clear-covid-19-infections-animal/
- https://journals.asm.org/doi/10.1128/spectrum.04998-22
経鼻SARS-CoV-2 RBD修飾ナノ粒子ワクチンは、シリアンハムスターモデルにおいてウイルスクリアランスを向上させる Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model
Devanshi R. Patel, Allen M. Minns, Derek G. Sim, Cassandra J. Field, Abigail E. Kerr, Talia A. Heinly, Erin H. Luley, SHOW ALL (14 AUTHORS), Troy C. Sutton
Microbiology Spectrum Published:9 February 2024
DOI:https://doi.org/10.1128/spectrum.04998-22
ABSTRACT
Multiple vaccines have been developed and licensed for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). While these vaccines reduce disease severity, they do not prevent infection. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor-binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4 A using cryogenicelectron microscopy. Using this RBD-grafted SpyCage scaffold (RBD + SpyCage), we performed two intranasal vaccination studies in the “gold-standard” pre-clinical Syrian hamster model. The initial study focused on assessing the immunogenicity of RBD + SpyCage combined with the LTA1 intranasal adjuvant. These studies showed RBD + SpyCage vaccination induced an antibody response that promoted viral clearance but did not prevent infection. Inclusion of the LTA1 adjuvant enhanced the magnitude of the antibody response but did not enhance protection. Thus, in an expanded study, in the absence of an intranasal adjuvant, we evaluated if covalent bonding of RBD to the scaffold was required to induce an antibody response. Covalent grafting of RBD was required for the vaccine to be immunogenic, and animals vaccinated with RBD + SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.
