Systemic immune responses induced by mucosal administration of lipopeptides without adjuvant

Abstract

We recently reported that parenteral injection of malaria palmitoyl‐tailed peptides without adjuvant efficiently induces B, Th and CTL responses. We now show that intranasal (IN) or sub‐lingual (SL) delivery of such lipopeptides induces strong systemic immune responses, as demonstrated by specific Th cell responses from the spleen as well as inguinal lymph nodes, and by the production ofhigh levels of serum antibodies. Overall, both types of responses were significantly higher than in parallel experiments in which the same lipopeptides were delivered by the subcutaneous (s.c.) route. Moreover, the mucosal route resulted in the preferential induction of IFN‐γ producing T cells and of IgG2a antibody production, as compared to the dominant IL‐4 and IgG1 responses obtained by the s.c. route, thus bringing a distinct advantage in the field of many infectious diseases and allergy. Possibly related to this Th1 response, we found that dendritic cells, the principal immune‐competent cells to encounter antigens within mucosal membranes, take up lipopeptide antigens more efficiently than macrophages. Mucosal immunization by lipidated peptides appears therefore as a novel, noninvasive vaccine approach that does not require the use of extraneous adjuvant and which, besides cost‐effectiveness, has attractive practical and immunological features.

Identification of Novel Immunodominant CD4+Th1-Type T-Cell Peptide Epitopes from Herpes Simplex Virus Glycoprotein D That Confer Protective Immunity

“…Identically prepared cultures were incubated with anti-CD8 MAb 53-6.7 (PharMingen) or with an isotype-matched control Ab, all at 10 g/ml. It has been previously shown that these antibodies show the expected specificities and function as expected (3,4). Cytokine analysis.…”

“…Twelve days after the second immunization, spleen and inguinal lymph nodes were removed and placed in ice-cold serumfree HL-1 medium supplemented with 15 mM HEPES, 5 ϫ 10 Ϫ5 M ␤-mercaptoethanol, 2 mM glutamine, 50 U of penicillin, and 50 g of streptomycin (GIBCO-BRL, Grand Island, N.Y.) (CM) (3,4). The cells were cultured in 96-well plates at 5 ϫ 10 5 cells/well in CM, with recall or control peptide at a 30-, 10-, 3-, 1-, or 0.3-g/ml concentration, as previously described (3,4 and the T-cell mitogen concanavalin A (Sigma, St. Louis, Mo.) were used as negative and positive controls, respectively.…”

HLA-A*0201-Restricted CD8+ Cytotoxic T Lymphocyte Epitopes Identified from Herpes Simplex Virus Glycoprotein D

“…Although the high degree of HLA polymorphism is often pointed to as a major hindrance to the use of epitope-based vaccines, this constraint can be dealt with through the inclusion of multiple supertype-restricted epitopes recognized in the context of diverse related HLA alleles and by designing mixtures of peptide-based vaccines with higher epitope densities (2,3,7,8,11,24,25). Broad population coverage can be established providing that epitopes corresponding to multiple HLA supertype families are incorporated into the vaccine.…”

CCR7-CCL19/CCL21-Regulated Dendritic Cells Are Responsible for Effectiveness of Sublingual Vaccination

“…The sublingual (s.l.) 3 route has been used for many years to deliver low-molecular-weight drugs, including small immunogenic peptides (5,6). The s.l.…”