Mucosal Immunization with Virus-Like Particles of Simian Immunodeficiency Virus Conjugated with Cholera Toxin Subunit B

Abstract

To enhance the efficiency of antigen uptake at mucosal surfaces, CTB was conjugated to simian immunodeficiency virus (SIV) virus-like particles (VLPs). We characterized the immune responses to the Env and Gag proteins after intranasal administration. Intranasal immunization with a mixture of VLPs and CTB as an adjuvant elicited higher levels of SIV gp160-specific immunoglobulin G (IgG) in sera and IgA in mucosae, including saliva, vaginal-wash samples, lung, and intestine, as well as a higher level of neutralization activities than immunization with VLPs alone. Conjugation of CTB to VLPs also enhanced the SIV VLP-specific antibodies in sera and in mucosae to similar levels. Interestingly, CTB-conjugated VLPs showed higher levels of cytokine (gamma interferon)-producing splenocytes and cytotoxic-T-lymphocyte activities of immune cells than VLPs plus CTB, as well as an increased level of both IgG1 and IgG2a serum antibodies, which indicates enhancement of both Th1-and Th2-type cellular immune responses. These results demonstrate that CTB can be an effective mucosal adjuvant in the context of VLPs to induce enhanced humoral, as well as cellular, immune responses.

Expression of two loopsV3 from HIV-1 fused to cholera toxin A2B subunit using Lactococcus lactis as a vector to induce immunity in mucosa

“…It has been reported that CTB induces a high titer of IgA antibody to HIV-1 (Bukawa et al, 1995;Kang et al, 2003) and IgG antibodies are induced less efficiently (Kim et al, 2004), like our results the IgG in serum were not significant as compared to IgA antibodies production.…”

Incorporation of Membrane-Anchored Flagellin into Influenza Virus-Like Particles Enhances the Breadth of Immune Responses

“…Similar phenomena have been observed with other pathogen-associated molecular patterns related to their corresponding TLRs. Previous studies showed that simian immunodeficiency virus VLPs conjugated with cholera toxin subunit B induced humoral and cellular responses that were stronger than those seen for a mixture of toxin with VLPs (21). It was also reported that when CpG-DNA is linked to ovalbumin, the protein uptake is facilitated by a receptor-mediated mechanism (50).…”

Adjuvants modulating mucosal immune responses or directing systemic responses towards the mucosa

“…III). However, it is interesting to note that the holotoxin stimulates stronger responses on a dose-bydose basis following intranasal delivery compared to the B subunit [52,108].…”