Humoral immune responses by prime-boost heterologous route immunizations with CTB-MPR649-684, a mucosal subunit HIV/AIDS vaccine candidate

CTB-MPR649-684 is a translational fusion protein consisting of the cholera toxin B subunit and a 36-residue peptide, MPR649-684, corresponding to the conserved membrane proximal ectodomain of gp41. CTB-MPR649-684 was previously shown to induce HIV-1 transcytosis-blocking antibodies in mice. In this report, we describe an effective immunization regimen for this novel anti HIV-1 vaccine-candidate. Bacterially-produced CTB-MPR649-684 was intranasally and/or intraperitoneally administered to investigate several prime-boost heterologous route immunization regimens. Mucosal priming with the adjuvant cholera toxin elicited significant levels of vaginal IgA and serum IgG specific to MPR649-684. Systemic boosting after mucosal priming enhanced the levels of serum and mucosal antibodies. Systemic priming induced a strong serum anti-MPR649-684 IgG response, which was efficiently recalled and augmented by either systemic or mucosal boosting. However, this regimen was less effective in inducing secretory anti-MPR649-684 IgA. The serum anti-MPR649-684 IgG subtype profile revealed that both IgG1 and IgG2a were induced in all the immunization regimens, and that mucosal co-administration of cholera toxin shifted the bias to the latter subtype. We concluded that, of the various immunization regimens examined here, mucosal priming with adjuvant followed by systemic boosting exhibited the best response in respect to either systemic or mucosal anti-MPR649-684 antibodies. Most importantly, mucosal antibodies elicited by this regimen significantly inhibited HIV-1 transcytosis in a human tight epithelium model. (c) 2006 Elsevier Ltd. All rights reserved.