Precision-engineering of subunit vaccine particles for prevention of infectious diseases

Abstract

Vaccines remain the best approach for the prevention of infectious diseases. Protein subunit vaccines are safe compared to live-attenuated whole cell vaccines but often show reduced immunogenicity. Subunit vaccines in particulate format show improved vaccine efficacy by inducing strong immune responses leading to protective immunity against the respective pathogens. Antigens with proper conformation and function are often required to induce functional immune responses. Production of such antigens requiring post-translational modifications and/or composed of multiple complex domains in bacterial hosts remains challenging. Here, we discuss strategies to overcome these limitations toward the development of particulate vaccines eliciting desired humoral and cellular immune responses. We also describe innovative concepts of assembling particulate vaccine candidates with complex antigens bearing multiple post-translational modifications. The approaches include non-covalent attachments (e.g. biotin-avidin affinity) and covalent attachments (e.g. SpyCatcher-SpyTag) to attach post-translationally modified antigens to particles.

Introduction of protein vaccine candidate based on AP65, AP33, and α-actinin proteins against Trichomonas vaginalis parasite: an immunoinformatics design

“…Mainly T cell and B cell epitopes are used for these types of vaccines. Antigens of appropriate conformation and function are often required to induce functional immune responses [ 14 , 15 ]. T. vaginalis -specific antibody responses and T cell-mediated immune responses may influence the outcome of the infection in terms of parasite clearance, persistence, or pathological responses [ 16 ].…”

“…In addition to T cell epitopes, the prediction of B cell epitopes plays an important role in the design of a vaccine against T. vaginalis [ 8 ]. Protein subunit vaccines are safer than whole-cell attenuated vaccines, but they often have a lower level of immunogenicity [ 14 ]. Antigens with different essential mechanisms and appropriate functions are required to design a suitable vaccine candidate to induce functional immune responses [ 12 ].…”

Polymeric epitope-based vaccine induces protective immunity against group A Streptococcus

“…We developed a new vaccine approach that is based on engineering endotoxin-free Escherichia coli to assemble spherical biopolymer inclusion which core is composed of the natural non-toxic polymer, polyhydroxybutyrate, and which surface densely displays antigens and epitopes of interest 19 – 21 . The one-step assembly of biopolymer particles (BPs) coated with antigens/epitopes inside engineered E. coli is high-yielding and enables cost-effective scalable manufacture of a synthetic subunit-based particulate vaccine which safety and efficacy against pathogens were previously shown 20 , 22 – 31 .…”

Changes in intestinal flora of mice induced by rEg.P29 epitope peptide vaccines

“…Most are synthetic and do not contain nucleic acids, allowing them to overcome some of the shortcomings of conventional vaccines, including improved efficiency and high specificity. 15 Here, we prepared three peptide vaccines, rEg.P29 T , rEg.P29 B , and rEg.P29 T + B , based on rEg.P29. Using a subcutaneous immunization model, we found through extensive experiments that immunization of mice with the peptide vaccines induced T helper cell type 1 (Th1)mediated cellular immune responses, leading to high levels of rEg.P29 or rEg.P29 B specific antibodies.…”

“…Peptide vaccines, which use antigenic epitopes to trigger immunity, are a relatively new type of vaccine. Most are synthetic and do not contain nucleic acids, allowing them to overcome some of the shortcomings of conventional vaccines, including improved efficiency and high specificity 15 . Here, we prepared three peptide vaccines, rEg.P29 T , rEg.P29 B , and rEg.P29 T + B , based on rEg.P29.…”