posted on 2021-08-11, 17:35authored byArmira Azuar, Mohini A. Shibu, Nomin Adilbish, Nirmal Marasini, Hong Hung, Jieru Yang, Yacheng Luo, Zeinab G. Khalil, Robert J. Capon, Waleed M. Hussein, Istvan Toth, Mariusz Skwarczynski
Peptide-based vaccines are composed
of small, defined, antigenic
peptide epitopes. They are designed to induce well-controlled immune
responses. Multiple epitopes are often employed in these vaccines
to cover strain variability of a pathogen. However, peptide epitopes
cannot stimulate adequate immune responses on their own and require
an adjuvant (immune stimulant) and/or delivery system. Here, we designed
and synthesized a multiepitope vaccine candidate against Group A Streptococcus
(GAS) composed of several B-cell epitopes (J8, PL1, and 88/30) derived
from GAS M-protein, universal PADRE T-helper cell epitope, and a polyleucine
self-adjuvanting unit. The vaccine components were conjugated together
(using mercapto-maleimide and azide–alkyne Huisgen cycloaddition
reactions) or delivered as a mixture. The conjugated multiepitope
vaccine candidate self-assembled into small nanoparticles and chain-like
aggregated nanoparticles (CLANs) that were able to induce the production
of J8-, PL1-, and 88/30-specific antibodies in mice. The multiepitope
conjugate and the physical mixture of conjugates bearing the individual
epitopes produced similar nanoparticles and induced comparable immune
responses. Hence, simple physical mixing can replace complex chemical
conjugation to produce multiepitope nanoparticles with equivalent
morphology and immunological efficacy. This greatly simplifies vaccine
production.