Lipidation as a novel approach to mucosal immunization.
We describe the design and development of a novel peptide-based approach for mucosal immunization. The design contains an amplified peptide chain as multiple antigen peptide (MAP) with a cluster of lipids. Such a design would confer on lipidated MAP the ability to self-assemble in water, mimicking enveloped viral particles. The importance of lipidation for mucosal immunization was confirmed by oral immunization with lipidated MAP in phosphate-buffered saline (PBS), which induced mucosal and systemic immune responses at local and distant sites, including sera and vaginal IgG as well as secretory IgA in saliva, vaginal secretions and fecal matter. T-cell proliferative responses were found in spleen, Peyer's patches and genital lymph nodes. In addition, significant splenic cytotoxic T-cell responses were also observed. No significant immune responses were observed with non-lipidated MAPs by oral delivery in PBS. Furthermore, these responses were selectively enhanced by different regimens, systemic priming and microparticle delivery. These results demonstrate the effectiveness of lipidated MAP for mucosal immunization to evoke both systemic and mucosal immune responses without the use of carrier or extraneous adjuvant.
Tam
J P
JP
Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN, USA.
Mora
A L
AL
Rao
C
C
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D016503:Drug Delivery Systems; D015195:Drug Design; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage / Q000276:immunology*; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D007376:Interleukin-2 / Q000096:biosynthesis; D050356:Lipid Metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology*; D011994:Recombinant Proteins
C112622:B1M-P3C protein, recombinant; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D010446:Peptide Fragments; D011994:Recombinant Proteins