posted on 2023-01-06, 19:44authored byYoung
Hun Chung, Britney A. Volckaert, Nicole F. Steinmetz
The SARS-CoV-2 pandemic has highlighted the need for
vaccines that
are effective, but quickly produced. Of note, vaccines with plug-and-play
capabilities that co-deliver antigen and adjuvant to the same cell
have shown remarkable success. Our approach of utilizing a nitrilotriacetic
acid (NTA) histidine (His)-tag chemistry with viral adjuvants incorporates
both of these characteristics: plug-and-play and co-delivery. We specifically
utilize the cowpea mosaic virus (CPMV) and the virus-like particles
from bacteriophage Qβ as adjuvants and bind the model antigen
ovalbumin (OVA). Successful binding of the antigen to the adjuvant/carrier
was verified by SDS-PAGE, western blot, and ELISA. Immunization in
C57BL/6J mice demonstrates that with Qβ - but not CPMV - there
is an improved antibody response against the target antigen using
the Qβ-NiNTA:His-OVA versus a simple admixture of antigen and
adjuvant. Antibody isotyping also shows that formulation of the vaccines
can alter T helper biases; while the Qβ-NiNTA:His-OVA particle
produces a balanced Th1/Th2 bias the admixture was strongly Th2. In
a mouse model of B16F10-OVA, we further demonstrate improved survival
and slower tumor growth in the vaccine groups compared to controls.
The NiNTA:His chemistry demonstrates potential for rapid development
of future generation vaccines enabling plug-and-play capabilities
with effectiveness boosted by co-delivery to the same cell.