Adjuvants: current status, clinical perspectives and future prospects.

Adjuvants represent a key issue for vaccines currently under development. Adjuvanticity is linked to the ability to stimulate the T-cell subsets that control the major features of specific immune responses: CD4+ TH1 and TH2 cells and CD8+ cells involved in cytotoxic T lymphocyte responses. Some well-defined immunomodulatory compounds can achieve this stimulation by inducing selective production of appropriate cytokines. Françoise Audibert and Luc Lise review the development of adjuvants and discuss how their combination with suitable vehicles should allow customization of adjuvant preparations capable of inducing protective immune responses better adapted to each type of pathogenicity.

Adjuvants: current status, clinical perspectives and future prospects.

Adjuvants represent a key issue for vaccines currently under development. Adjuvanticity is linked to the ability to stimulate the T-cell subsets that control the major features of specific immune responses: CD4+ TH1 and TH2 cells and CD8+ cells involved in cytotoxic T-lymphocyte responses. Some well-defined immunomodulatory compounds can achieve this stimulation by inducing selective production of appropriate cytokines. Françoise Audibert and Luc Lise review the development of adjuvants and discuss how their combination with suitable vehicles should allow customization of adjuvant preparations capable of inducing protective immune responses better adapted to each type of pathogenicity.

Role of the proline residues on the immunogenic properties of a P. falciparum circumsporozoite peptide linked to a carrier protein.

The circumsporozoite (CS) protein of P. falciparum contains an immunodominant epitope, NADP, that is repeated 37 times in the native molecule. The presence of proline in the coat proteins of the Plasmodium parasite at various developmental stages and strains is a frequent occurrence. In this study we evaluate the influence of substitution of proline residues by glycine on the immunogenic behavior of two tandemly repeated peptides linked via glutaraldehyde to a protein carrier: The (NANP)4 P. falciparum circumsporozoite peptide and its glycine-substitute analog, (NANG)4. The results obtained show that the (NANP)4 induces antibodies which recognize the peptide free in solution, bound on a solid phase, and linked to a carrier protein. It has been previously reported that such antibodies recognize the antigenic sites of the peptide in the native protein on the surface of the sporozoite. Antibodies raised against (NANG)4 in the same experimental conditions as (NANP)4, cannot recognize the peptide free in solution or bound to the solid phase. However, these antibodies can react with the peptide when it is linked to a protein carrier. The coupling of a glycine-containing analog to a carrier results in a significant shift in its conformation, allowing it to be recognized by the antibodies.

Enhanced epitopic response to a synthetic human malarial peptide by preimmunization with tetanus toxoid carrier.

Successful human vaccination by synthetic malarial sporozoite peptides may depend on the choice of an appropriate carrier. Tetanus toxoid (TT) has been proposed because of its safe and widespread use in humans. Paradoxically, however, prior exposure to this toxoid vaccine could produce specific epitopic suppression against synthetic malarial peptides conjugated to this same protein as carrier. Indeed, we have previously reported that such a phenomenon can occur in the case of a synthetic vaccine made with a streptococcal peptide conjugated to TT. Our present study shows that similar results can be observed in mice preimmunized with TT 1 month before the administration of a conjugate containing TT and a Plasmodium knowlesi peptide. Analysis of the isotypic pattern of the antipeptide response showed that the immunoglobulin G1 (IgG1) subclass and especially the IgG2a and IgG2b subclasses were suppressed. In contrast, when a sporozoite peptide from Plasmodium falciparum was coupled to TT, the total antipeptide antibodies and particularly the IgG1 subclass were enhanced by preimmunization by TT. This increase of antipeptide antibodies was correlated with a greater ability of the sera to neutralize sporozoite infectivity. These results indicate that prior exposure to TT does not systematically impair the antibody response against a peptide administered as a peptide-TT conjugate.