Abstract
The 4th International Workshop in Vaccine Adjuvants and Parasitic Vaccines (Adjuvant 2008), hosted by the Cuban Society for Immunology, attracted approximately 70 scientists from 22 countries. The meeting goal was mainly to share recent progress and discuss future challenges regarding vaccine adjuvants for the development of mucosal vaccines, as well as antiparasitic vaccines. Five keynote addresses, 21 oral presentations and 28 posters were presented, and the meeting was ended with a ‘hot-topic’ session discussing future challenges. This article highlights the most important issues discussed.
Mucosal immunity & vaccine adjuvants
Development and widespread use of vaccines stands out as one of the most successful public-health interventions with a major impact on global health. The recent shift away from traditional vaccines toward subunit/recombinant vaccines calls for the development of safe and potent vaccine adjuvants and delivery systems that can amplify and direct vaccine-specific immunity. The vast majority of infections either invade the body through, or establish infection in, the mucosal tissues. Thus, a better understanding of mucosal immunity and the development of mucosal vaccines represent two of the greatest challenges in vaccine development. P Brandtzaeg (University of Oslo, Norway) highlighted the importance of the antibody response in immunity at the mucosal tissues and that systemic IgG antibodies, in addition to secretory IgA (SIgA) and innate immune mechanisms, are involved in mucosal protection. The mechanism through which nasal immunization leads to humoral immunity in the respiratory tract and the female genital tract was discussed. Salivary SIgA antibodies may reflect mucosal immunity in the nasopharyngeal-associated lymphoid tissue. The importance of a noninvasive method to determine GI tract immunity was also discussed.
AM Harandi (University of Gothenburg, Sweden) reviewed recent progress in the development of mucosal adjuvants for immunity in the female genital tract against sexually transmitted infections. He presented results on the potential of Toll-like receptor (TLR) agonists as mucosal adjuvants for immunity against genital herpes simplex virus type 2 (HSV-2) infection in mice, and showed the potential of α-galactosylceramide, as a Toll-free immunomodulatory adjuvant, together with glycoprotein D (gD) from HSV-2 for the induction of protection against an otherwise lethal HSV-2 infection. By using a well-established mouse model, D Medaglini (University of Sienna, Italy) showed that nasal immunization is an optimal route to mount CD4+ and CD8+ T-cell immune responses at the local site, as well as activation of disseminating effector cells to distant mucosal sites such as the female genital tract.
O Pérez (Finlay Institute, Cuba) showed results on the mucosal adjuvant effects of the Finlay Institute adjuvant (Adjuvant Finlay Cochleate 1 [AFCo1]); derived from serogroup B Neisseria meningitides. J del Campo (Finlay Institute, Cuba) described the nasal adjuvant effect of AFCo1 when used together with HSV-2 gD protein for induction of protective immunity against genital herpes infection in mice. R Acevedo (Finlay Institute, Cuba) reported the development of Vibrio cholerae-based cochleate adjuvant (AFCo2). Finally, L Guilherme (Heart Institute, Brazil) showed results on the potential of AFCo1 to be used as a nasal or systemic adjuvant for induction of immunity to T- and B-cell epitopes from Streptococcus pyogenes.
Parasitic vaccines
Parasitic infections, including the most devastating malarial infection, cause serious public-health problems in many poor countries. Nonetheless, there is no parasitic vaccine licensed for human use. G Corradin (University of Laussanne, Switzerland) highlighted the importance of bioinformatics/chemical synthesis approaches for the rapid identification of molecules that can be targeted by biologically active antibodies and, thus, be used as vaccine candidates for parasitic infections. M Arévalo-Herrera (Universidad del Val, Colombia) demonstrated promising results on two satisfactory Phase I trials using Plasmodium vivax circumsporozoite synthetic peptide as antigen together with Montanide™ as an adjuvant. New strategies to develop transmission-blocking vaccines against P. vivax infection were also discussed. O Noya (University of Venezuela, Venezuela) showed that chemically synthesized polymerizable peptides derived from Schistosoma mansoni enzymes were immunogenic and able to protect outbred mice when used together with Freund’s adjuvant. O Pérez reported the development of Plasmodium berghei rat models to study malaria during pregnancy. A Flixer and S León-Cabrera (Universidad Nacional Autónoma de México, Mexico) presented results on an experimental oral vaccine based on calreticulin from Taenia solium and cholera toxin (CT) capable of reducing tapeworm number and altering the anchorage site of the worm in hamsters.
Mechanism of action of vaccine adjuvants
J Hoebeke (Emeritus Prof., Belgium) claimed that rational design of immune adjuvants has been hampered by the lack of structural knowledge on adjuvant and their receptors. He showed data on the enhanced immunostimulatory effect of CpG oligodeoxyneucleotides when combined with carbon nanotubes; and that a synthetic mini-CD40L could be used as adjuvant to induce protection against an experimental Trypanosoma cruzi infection. AW Heath (University of Sheffield, UK) reported that low doses of anti-CD40 monoclonal antibody has adjuvant activity in experimental models. S Ascarateil (Seppic, France) presented data on how the process used to prepare water-in-oil (W/O) emulsions may influence quality, stability and particle size of dispersed phase, which in turn influence the immunogenicity of antigen. The importance of the use of standardized and reproducible W/O emulsions was discussed. V Ferro (University of Strathclyde, UK) showed that bilosomes could serve as an oral delivery system with the ability of protecting entrapped antigen against degradation in the GI tract and induction of mucosal and systemic immune response. S Vendetti (Instituto Superiore di Sanita, Italy) showed that CT could induce the differentiation of monocytes into an activated macrophage-like population, and that CT is able to induce an immune response similar to extracellular cAMP, suggesting that CT is able to transmit and amplify its immunomodulatory effects on the innate as well as the adaptive immune system. L García (Finlay Institute, Cuba) reviewed the use of different bacterial outer membrane proteins and proteoliposomes as vaccine adjuvants. B Wizel (Intercell, Austria) reviewed recent results on the use of IC31™ adjuvant in experimental vaccine development as a safe and potent inducer of humoral as well as Th1-type immune responses, including CD8+ T-cell responses.
Tumor vaccines
LE Fernández (Center of Molecular Immunology, Cuba) showed that a combination of active immunotherapy and high-dose chemotherapy in advanced cancer patients could be an alternative to disappointing previous strategies; although this approach is still associated with myelosuppression and lymphopenia. The potential of very small size proteoliposomes (VSSPs) as a nanoparticulated delivery system containing TLR2 and TLR4 agonists as an adjuvant for anticancer vaccines was discussed. G Garrido (Center of Molecular Immunology, Cuba) showed that immunization of mice with the extracellular domain of murine EGF using either Freund’s complete adjuvant (FCA) or VSSP as adjuvants elicited highly specific IgG antibody and CD8+ T-cell responses with a potent antimetastatic effect in a mouse model of EGFR+ D122 lung carcinoma. M Loeffler (Tyrolean Cancer Research Institute, Austria) reported that engineered Salmonella typhimurium encoding LIGHT inhibited growth of primary tumors, as well as the dissemination of pulmonary metastases, which suggests that non-virulent bacteria can be exploited as targeting vehicles for local generation of therapeutic proteins in tumors.
Hot topics
The following topics concerning recent advances and future challenges in the field were discussed in the hot topics session.
• SIgA has an innate-like activity providing a much greater cross-protection compared with serum IgG. Nevertheless, little is known about the mechanism of innate SIgA induction; how it could be exploited to enhance protection and memory;
• How regulations imposing antibody titers or functional antibody assay as exclusive correlates of protection could influence/hamper the selection of good adjuvant–vaccine candidates? What is the contribution of other immune parameters, such as antibody isotypes, T-cell types (Th1/Th2/Th17) and SIgA, to immune protection?
• How to overcome likely cultural and psychological barriers facing some novel mucosal routes of vaccination (e.g., vaginal and rectal)?
• More structural vaccinology looking for correlation between structure and function is needed;
• It remains elusive as to how to induce IgE antibody response important for immunity against helminth infection. What are the correlates of protection in parasitic infections (e.g., infection with P. vivax)?
Conclusion
The impact of immunology and biotechnology on public-health issues, such as reductions in infant mortality and prevention of some life-threatening infectious diseases, was highlighted by A Lage (Center of Molecular Immunology, Cuba) during the opening ceremony of the meeting. It was also discussed during the meeting that rational design of safe and potent vaccine adjuvants, as well as protective antigens in light of recent developments in immunology, molecular biology and biochemistry, is urgently needed.
Financial & competing interests disclosure
The authors have no relevant affiliation or financial involvement with any organization or entity with a financial interest in or fanatical conflict with the subject matter or material disclosed in the manuscript. This includes employment, consultations, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing support was utilized in the production of this manuscript.