Enhanced Mucosal Immune Responses to HIV Virus-Like Particles Containing a Membrane-Anchored Adjuvant

Abstract

Previously, a modified HIV Env protein with a heterologous membrane anchor was found to be incorporated into HIV virus-like particles (VLPs) at 10-fold-higher levels than those of unmodified Env. To further improve the immunogenicity of such VLPs, membrane-anchored forms of bacterial flagellin (FliC) or a flagellin with a truncated variable region (tFliC) were constructed to be incorporated into the VLPs as adjuvants. HIV-specific immune responses induced by the resulting VLPs were determined in a guinea pig model. The VLPs induce enhanced systemic antibody responses by either systemic or mucosal vaccination and enhanced mucosal immunity by a mucosal immunization route, as demonstrated by high levels of HIV-specific serum IgG and mucosal IgG and IgA. The quality of the antibody responses was also improved, as shown by enhanced neutralization capacity. VLPs incorporating FliC were more effective in inducing systemic responses, while VLPs containing tFliC were more effective in inducing mucosal IgA responses. The IgG titers in sera were found to last for at least 5 months without a significant drop. These results indicate that HIV VLPs incorporating high levels of Env and a molecular adjuvant have excellent potential for further development as a prophylactic HIV vaccine.

Pseudomonas aeruginosa Recombinant Flagellin Induced Poly-Isotypic Humoral Immune Responses in the Balb/C Mice

“…Furthermore, we have shown that immunization of mice with r-fla-A could remarkably increase survival of mice infected with homologous strain (PAK) in the burn wound infection, but slight protection was observed in mice infected with heterologous strain PAO1 (unpublished result). Antibody is an important factor to control the pseudomonas infection in the active or passive form of vaccination (28). As the results of our study have shown, r-fla-A induced poly-isotypic humoral immune responses and considering that each antibody isotype may have a distinct function in the immune responses, this confirmed that r-fla-A is a strong inducer of humoral immune responses in which in the level and bioactivity of products are higher.…”

Co-delivery of GPI-anchored CCL28 and influenza HA in chimeric virus-like particles induces cross-protective immunity against H3N2 viruses

“…The cVLPs containing GPI-anchored CCL28 (HA/M1/GPI-CCL28 VLPs) were produced by co-infection of SF9 cells with rBVs expressing HA, M1, and GPI-CCL28 at the MOIs of 2:1:1 (35). At 60 h post-infection, VLPs were concentrated from cell culture supernatant by porous fiber filtration using the Quixstand benchtop system (GE Healthcare, Uppsala, Sweden) and purified using sucrose density gradient centrifugation (31).…”

Mucosal vaccine delivery: Current state and a pediatric perspective

“…This prevents stimulation of TLR5 by commensal bacteria, and TLR5-activation occurs only from invading bacteria [231–233]. The adjuvant effect of flagellin has been tested intranasally for many vaccines such as against influenza virus [234, 235], tetanus toxin [236], malaria [237], Schistosoma mansoni [238], and HIV [239]. …”