Coupling Peptide Antigens to Virus-Like Particles or to Protein Carriers Influences the Th1/Th2 Polarity of the Resulting Immune Response

Abstract

We have conjugated the S9 peptide, a mimic of the group B streptococcal type III capsular polysaccharide, to different carriers in an effort to elicit an optimal immune response. As carriers, we utilized the soluble protein keyhole limpet hemocyanin and virus-like particles (VLPs) from two plant viruses, Cowpea Chlorotic Mottle Virus and Cowpea Mosaic Virus. We have found that coupling the peptide to the soluble protein elicits a Th2 immune response, as evidenced by the production of the peptide-specific IgG1 antibody and IL-4/IL-10 production in response to antigen stimulation, whereas the peptide conjugated to VLPs elicited a Th1 response (IgG2a, IFN-γ). Because the VLPs used as carriers package RNA during the assembly process, we hypothesize that this effect may result from the presence of nucleic acid in the immunogen, which affects the Th1/Th2 polarity of the response.

Virus‐like particles for vaccination against cancer

“…The exterior or interior surface of VLPs can be functionalized and modified to display the antigens or epitopes of interest by different means: • Chemical coupling • Genetic fusion and engineering • Peptide conjugation , Brune et al (2016); Kaczmarczyk, Sitaraman, Young, Hughes, and Chatterjee (2011); Martin Caballero et al (2012); Pomwised, Intamaso, Teintze, Young, and Pincus (2016); Pumpens (2016); Tegerstedt et al (2005); Zeltins et al (2017) Immunostimulatory molecules Some VLPs assemble around RNA fragments (noninfectious or replication competent) during the expression process in host cells. VLPs can also be disassembled and reassembled in the presence of different TLR-ligands such as oligodeoxynucleotides (CpGs) (TLR-9 ligand), polyGLU, ssRNA (TLR 7/8 ligand) or dsRNA (TLR-3 ligand) Dash, Federica, Ottenbrite, and Chiellini (2011); Kawano, Matsui, and Handa (2018); Sioud (2006); ; Gomes et al (2019).…”

Virus‐like particles: Next‐generation nanoparticles for targeted therapeutic delivery

“…Alternatively, a series of compounds based on maleimide readily and irreversibly form thioether linkages with cysteine residues at a pH between 6.5 and 7.5. This attachment strategy has been used to display cell‐penetrating peptides, fluorescent probes, and heterologous peptides and proteins on the surfaces of MS2, P22, CCMV, and CPMV VLPs …”

Yeast as an expression system for producing virus-like particles: what factors do we need to consider?

“…One is to display a heterologous epitope on the VLP surface by genetic engineering, and the other to display it on the VLP surface by chemical conjugation. The former approach has been used for VLPs from HBV, hamster polyomavirus and enterovirus 71 (Pumpens et al 2002;Li et al 2004;Mazeike et al 2012;Pleckaityte et al 2015;Zhao et al 2015). Hepatitis B virus surface antigen VLPs tolerated insertion of an HPV E7 epitope (19 amino acids) and the hepatitis E antigen (56 amino acids) (Pumpens et al 2002;Li et al 2004).…”

“…The former approach has been used for VLPs from HBV, hamster polyomavirus and enterovirus 71 (Pumpens et al 2002;Li et al 2004;Mazeike et al 2012;Pleckaityte et al 2015;Zhao et al 2015). Hepatitis B virus surface antigen VLPs tolerated insertion of an HPV E7 epitope (19 amino acids) and the hepatitis E antigen (56 amino acids) (Pumpens et al 2002;Li et al 2004). Hamster polyomavirus VP1 VLPs have great potential for delivering foreign epitopes because they tolerate insertions of various sizes of foreign epitope (9-120 amino acids) (Gedvilaite et al 2000(Gedvilaite et al , 2004.…”

“…This result shows that carrier VLPs can be turned into particles that preferentially display foreign antigen by chemical conjugation. Virus-like particles of cowpea chlorotic mottle virus or cowpea mosaic virus have been conjugated with group B streptococcal type III capsular polysaccharide using the heterobifunctional cross-linking reagent, sulfo-SMCC, and the resulting VLPs induced specific antibody responses to the foreign antigen (Pomwised et al 2016).…”