A group from Scripps Research Institute has reported that a broadly neutralizing antibody strong to SARS-CoV-2 variants could be induced by using SARS-CoV-2 nanoparticles as a vaccine.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010731/
The main stream of the current vaccines is using platforms which deliver the recombinant SARS-CoV-2 spike as an antigen such as mRNA-encapsulated liposomes (e.g., BNT162b2 and mRNA-1273), adenovirus vectors (e.g., ChAdOx1 nCoV-19 [AZD1222], CTII-nCoV, Sputnik V, and Ad26.COV2.S). There vaccines are compatible with B.1.1.7 variant, but a notable loss of efficacy was reported for B.1.351 and P.1 variants. Therefore, it is required to develop vaccines that can elicit a broadly neutralizing antibody (bNAb) response to SARS-CoV-2 variants. For this purpose, those vaccines have to induce long-lived germinal center (GC) reactions to activate precursor B cells, stimulate affinity maturation, and form long-term immune memory.
The SARS-CoV-2 spike protein is a trimer of S1-S2 heterodimers. The S1 subunit contains a receptor-binding domain (RBD) to initiate infection. The S2 subunit consists of a fusion peptide (FP) and heptad repeat regions 1 and 2 (HR1 and HR2). Authors designed an HR2-deleted glycine-capped spike (S2GΔHR2) to increase the spike stability, and assembled those spikes on a nanoparticle platform called SApNP using I3–01v9 60-mers as a linker (S2GΔHR2-10GS-I3-01v9-LD7-PADRE (I3-01v9-L7P)). The I3–01v9-LP7 presents 20 stabilized spikes.
Using S2GΔHR2-10GS-I3-01v9-L7P as a vaccine, a bNAb were induced showing compatible titers for B.1.1.7, B.1.351, and P.1 variants. Compared with the soluble spike, this nanoparticle showed 6-fold longer retention, 4-fold greater presentation on follicular dendritic cell dendrites, and 5-fold higher germinal center reactions in lymph node follicles. The reason of this effect is not clear yet, but would be related to the size effect.
