Poly(hydrophobic Amino Acids) and Liposomes for Delivery of Vaccine against Group A Streptococcus

Abstract

Adjuvants and delivery systems are essential components of vaccines to increase immunogenicity against target antigens, particularly for peptide epitopes (poor immunogens). Emulsions, nanoparticles, and liposomes are commonly used as a delivery system for peptide-based vaccines. A Poly(hydrophobic amino acids) delivery system was previously conjugated to Group A Streptococcus (GAS)-derived peptide epitopes, allowing the conjugates to self-assemble into nanoparticles with self adjuvanting ability. Their hydrophobic amino acid tail also serves as an anchoring moiety for the peptide epitope, enabling it to be integrated into the liposome bilayer, to further boost the immunological responses. Polyleucine-based conjugates were anchored to cationic liposomes using the film hydration method and administered to mice subcutaneously. The polyleucine-peptide conjugate, its liposomal formulation, and simple liposomal encapsulation of GAS peptide epitope induced mucosal (saliva IgG) and systemic (serum IgG, IgG1 and IgG2c) immunity in mice. Polyleucine acted as a potent liposome anchoring portion, which stimulated the production of highly opsonic antibodies. The absence of polyleucine in the liposomal formulation (encapsulated GAS peptide) induced high levels of antibody titers, but with poor opsonic ability against GAS bacteria. However, the liposomal formulation of the conjugated vaccine was no more effective than conjugates alone self-assembled into nanoparticles.

Development of Methamphetamine Conjugated Vaccine through Hapten Design: In Vitro and In Vivo Characterization

“…Hence, this novel platform has several new aspects compared to the existing protein-based anti-METH vaccine platforms. One can further optimize antibody responses by using self-adjuvanting tricomponent vaccines that include antigen-glycoprotein-universal T helper epitope PADRE and Pam 3 CysSer adjuvant [51][52][53] or the use of nanoparticles [54][55][56]. Previous research on the efficacy and stability of relevant candidate MS vaccine using oxidized mannan conjugated with antigenic epitope peptide MOG35-55 is in line with and supports the findings of this study [57,58].…”

Utilizing murine dendritic cell line DC2.4 to evaluate the immunogenicity of subunit vaccines in vitro

“…This implies that CD40 may serve as a reliable marker for indicating the production levels of TNF-α and IL-10. As previously reported, all poly(hydrophobic amino acids)-containing vaccine formulations (J8-K(V 10 )-PADRE, J8-K(F 10 )-PADRE, J8-K(L 10 )-PADRE, J8-K(L 15 )-PADRE, and L 15 -PADRE-J8) self-assemble into nanoparticles ( 13 , 21 , 27 , 28 ), which facilitate their recognition by APCs, including DCs, thereby enhancing the internalization of vaccine components and further accelerating the processing of antigens and presentations by DCs. This was in line with our findings that naked antigen (J8, or PADRE-J8) without a nanoparticulate delivery system could not upregulate CD40, MHC-II, CD80 or CD86 expression on DC2.4 cells.…”

Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer

“…In our previous attempts to develop efficient vaccine delivery systems, we have demonstrated that conjugation of the polyleucine moiety to a peptide antigen greatly enhanced antigen-specific humoral immune responses [ 20 , 21 , 23 , 24 , 25 , 26 , 27 ]. We also found that the polymer–antigen conjugate D-8Qm once formulated into liposomes ( L1 ) was able to eradicate, to some extent, seven-days-old cancer in mice [ 27 ].…”

“…The observed nitrogen–carbon ratio for D-8Qm (N/C = 0.115) was higher than that of the polymer alone (N/C= 0.017) and corresponded to 83% of the substitution rate of the dendrimer with 8Qm peptide (similar to that previously reported at 85% [ 19 ]). Both D-8Qm and pLeu-8Qm , as amphiphilic conjugates, were easily incorporated (anchored) into liposomes [ 19 , 21 ] to form L1 and L2 , respectively ( Figure 1 ).…”

“…This method is fully automated and used to incorporate desired peptide epitopes into molecules within a single procedure. Moreover, pHAAs, such as polyleucine ( pLeu ), mimic the transmembrane fragments of proteins, which are often leucine-rich and, therefore, have been used as anchoring moieties for the incorporation of peptide antigen in liposomal delivery systems [ 21 ]. While pHAA systems are still classified as polymeric, they are tremendously different to other polymeric systems currently used for vaccine delivery [ 22 ].…”