New strategies to overcome the drawbacks of currently available flu vaccines.

Vaccination represents the most efficient tool to control morbidity and mortality resulting from influenza infections in humans. The currently licensed influenza vaccines provide good protection levels in healthy adults, whereas lower protection is generally achieved in ageing individuals who are at a higher risk of developing severe clinical manifestations. Future improvements in influenza vaccines should address the needs of high risk groups including the elderly, small children and chronic patients. Recently, due to the increased incidence of avian influenza pandemic outbreaks, the prevention of a potential human influenza pandemic turned into another crucial issue in the influenza vaccination field. The development and validation of manufacturing processes for efficient and safe pandemic vaccines became one of the top priorities of health, regulatory and funding agencies all over the world. In the pandemic context, the development of novel vaccines administered via the mucosal route may play a significant role by reducing virus shedding from infected individuals. This chapter provides insights in the limitations of existing manufacturing processes, new approaches to overcome limitation in vaccine production, mechanisms of action of current vaccines and discuss potential strategies to improve the immunogenicity and efficacy of influenza vaccines.

Liposomes and virosomes as delivery systems for antigens, nucleic acids and drugs.

Lipid-based vesicles are a very promising approach to treat diseases such as cancer, chronic infections and auto-immunity. Modern drug encapsulation methods allow efficient packing of therapeutic substances inside liposomes, thereby reducing the systemic toxicity of the drugs. Specific targeting can enhance the therapeutic effect of the drugs through their accumulation at the diseased site. In the vaccine field, the integration of functional viral envelope proteins into liposomes has led to an antigen carrier and delivery system termed a virosome, a clinically proven vaccine platform for subunit vaccines with an excellent immunogenicity and tolerability profile.

T cell-specific immune response induced by bacterial ghosts.

BACKGROUND: Bacterial ghosts, genetically inactivated Gram-negative bacterial pathogens, possess significant advantages over commonly used vaccination technologies. The autolysis of the bacteria, by the expression of a cloned viral gene, results in empty bacterial envelopes through the expulsion of cytoplasmic content. Immunostimulatory properties are generally presented through the targeting of professional antigen-presenting cells (APCs), such as macrophages and dendritic cells (DCs). MATERIAL/METHODS: This study investigated the interactions between porcine antigen-presenting cells and bacterial ghosts derived from the bacterial pathogen Actinobacillus pleuropneumoniae. The maturation process of DCs and their generation of immune responses to bacterial ghosts was shown by the expression of activation markers on their surface, as well as in the functional tests. RESULTS: A population of porcine APCs was generated from PBS by incubation with rpo-GMCSF and rh-IL-4. The cells expressed SWC3, MIL-2, CD80/86 molecules, as well as a high level of MSA3 molecules. The internalization of bacterial ghosts by the cells resulted in increased expression of MSA3 molecules. The capacity of T cells to proliferate when induced by bacterial ghosts was 4 times higher in the cultures including APCs than in cultures stimulated with bacterial ghosts only. CONCLUSIONS: We found that antigen-presenting cells have the capacity to stimulate specific T cells after the internalization and processing of Actinobacillus ghosts, as demonstrated by a strong specific T-cell response generated against the ghost antigens.

Anti-metastatic activity of hapten-modified autologous tumor cell vaccine in an animal tumor model.

We used mice from which the primary 410.4 mammary carcinoma had been surgically excised to assess the anti-metastatic activity of low-dose cyclophosphamide (CY) followed by vaccination with dinitrophenyl (DNP)-modified, irradiated, autologous tumor cells (ATC) admixed with bacille Calmette-Guérin (BCG). Our studies revealed that CY treatment of mice followed by vaccination with DNP-modified. irradiated, ATC admixed with BCG improved the relapse-free survival compared to the survival of mice receiving either CY followed by vaccination with unmodified, irradiated, ATC admixed with BCG, or saline (control group). In addition, our studies demonstrated the importance of CY administration in eliciting the therapeutic effect of DNP-modified ATC vaccine against metastatic disease. The therapeutic effect of CY followed by DNP-modified ATC vaccine was abrogated by depletion of CD4(+) or CD8(+) T-cells, illustrating the importance of both T-cell subsets for the anti-metastatic effect of this therapeutic protocol. In addition, neutralizing anti-IFN-gamma monoclonal antibody (mAb), or neutralizing anti-tumor necrosis factor (TNF) mAb reduced the relapse-free survival of mice treated with CY followed by DNP-modified ATC vaccine, indicating the importance of both cytokines for the realization of the anti-metastatic effect of this therapeutic protocol. Since the therapeutic protocol used in our studies was similar to that employed by Berd et al. as postsurgical adjuvant therapy in cancer patients and yielded a comparable anti-metastatic effect, the information obtained from the current studies with our clinically relevant experimental tumor model is expected to shed light on the mechanism(s) by which the anti-metastatic effect of this post-surgical adjuvant therapy is realized in cancer patients.