Enhanced mucosal and systemic immune response with intranasal immunization of mice with HIV peptides entrapped in PLG microparticles in combination with Ulex Europaeus-I lectin as M cell target

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• 作者：Monika Manocha ; Pramod Chandra Pal ; K.T. Chitralekha ; Beena Elizabeth Thomas ; Vinita Tripathi ; Siddhartha Dutta Gupta ; Ramesh Paranjape ; Smita Kulkarni and D. Nageswara Rao
• 关键词：Peptide ; Microparticle ; Ulex Europaeus-I lectin ; Secretory IgA
• 刊名：Vaccine
• 出版年：2005
• 出版时间：1 December 2005
• 年：2005
• 卷：23
• 期：48-49
• 页码：5599-5617
• 全文大小：603 K

文摘

The predominant route of HIV infection is through the sexual transmission via M cells. Most of the peptide and protein vaccines show poor transport across the epithelial barrier and are commonly administered by parenteral route. In the present study four HIV peptides from envelope (gp41-LZ (leucine zipper), gp41-FD (fusion domain) and gp120-C2) and regulatory (Nef) region in poly lactic-co-glycolide (PLG) microparticle delivery were evaluated in mice of outbred and with different genetic background to compare immune response versus MHC restriction. Out of the combinational and single routes of immunization attempted, the single route maintained the IgG, IgA and sIgA in sera and washes for longer duration as compared to combinational routes in which the response was declined. The study demonstrated that single intranasal immunization offered significantly higher immune response (p < 0.05) over oral and rectal mucosal routes in terms of inducing systemic as well as mucosal response. Also, the specific activity measurement of IgA and IgG in sera and sIgA in washes were correlating to the antibody titers. However, the intramuscular route of immunization generated systemic response only. The entrapment of plant lectin UEA-1 a ligand specific for M cells in microparticle further enhanced the immune response in all the mucosal routes. The IgG isotypes generated were of IgG1 and IgG2a/2b in sera for all the peptides. The T cell proliferation response study with and without UEA-1 lectin in microparticles showed significantly high (p < 0.05) stimulation index (SI) with intranasal immunization for all the peptides from cells collected from spleen (SP), peyer's patches (PP) and lamina propria (LP) with SI in the order LP cells > PP ≥ SP. The cytokine measurement profile of IL-2, IFN-γ and IL-6 and low levels of IL-4 in the cultural supernatants of SP, PP and LP showed mixed CD4⁺ Th1 and Th2 immune response. The p24 assay showed high percent inhibition of HIV-IIIB virus with sera and washes obtained from intranasal route. Thus, overall the study highlighted the combination of UEA-1 lectin with HIV peptides in microparticles through intranasal immunization generated systemic as well as mucosal immune response.