FORUM
Eur. J. Immunol. 2014. 44: 1573–1574
News & EFIS The EFIS-EJI Ruggero Ceppellini Advanced School of Immunology Malaria, Tuberculosis and HIV/AIDS: Novel vaccination strategies against the three major killers
Novel and innovative vaccines against the three most deadly infectious diseases (Malaria, Tuberculosis (TB) and HIV/AIDS) are being investigated around the world, both in leading research laboratories and in clinical trials. For the past 22 years, the EFIS-EJI Ceppellini School (www.ceppellini.it) has focused on topical aspects of immunology [1], and the 2013 course focused on these deadly diseases under the direction of Stefan H.E. Kaufmann (Max Planck Institute, Berlin) and Francesca Chiodi (Karolinska Institute, Stockholm). This meeting was held in the shadow of the volcano Vesuvius (Castellammare di Stabia) the 16–20 October 2013 (Fig. 1). The aim of this course was to spread the newest advancements in the field among scientists and health operators, especially those coming from developing countries, where the mortality for such diseases reaches the highest peaks. Vaccines represent the best tool to prevent infectious diseases, as proven by those against polio, smallpox, measles, mumps, rubella, hepatitis B, diphtheria, tetanus, pneumococcal pneumonia, and meningococcus. There is founded hope that in the very near future novel vaccines will be developed to fight also malaria, tuberculosis and HIV/AIDS, although 100% protection from all three diseases seems an overly ambitious goal, since other factors must be taken into account, such as poverty and malnutrition.
Understanding the mechanisms by which those pathogens evade the body’s immune response is of course of crucial importance in developing strategies to construct novel vaccines. The course focused on various aspects of the pathophysiology of infection, especially on the immune regulation at host-infectious agent interface. As underlined by director Stefan Kaufmann [2], some vaccines already exist, but are not universally effective, i.e. for bacille Calmette-Gu´erin (BCG) that only protects newborns from severe forms of disseminated TB but fails to prevent the most prevalent form, pulmonary TB, in all age groups. A recent vaccine for AIDS, using RV144, didn’t show satisfactory protection, whereas RTS vaccine for malaria offers some but not complete protection. Therefore, a careful comparison of host responses and markers of disease progression or regression in protected versus non-protected individuals is necessary. Rino Rappuoli told the audience of the great improvements in vaccine technology, the so-called third wave of vaccine development, characterized by optimal design antigens, adjuvants and delivery systems, derived from the new acquisitions on the structure of the antigens and epitopes and their interaction with the human immune system. As emerged in later discussions, these exciting and very promising advancements in vaccine making technology clash against the difficulty of delivering even existing solutions to resource-limited settings, i.e. third world countries, compelling us to find ways to accelerate a more efficient and less costly decision making process in selecting new vaccine candidates. The HIV/AIDS session was opened by the lecture of Robin Weiss, who shared his vast experience and wisdom in the field, discussing the successes and failures of the last 30 years of HIV science
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
[3]. This was followed by the presentation of Thumbi Ndung’u, that focused on the study of CD8+ T cells and Gag-protease interactions in HIV-1-infected individuals in South Africa, showing that an intricate balance between those cells and viral fitness is required for HIV-1 immune control. Opening the TB session, Anne O’Garra presented the problem of the diagnostic recognition of individuals who would progress in the disease, for which there are no tests available. Identifying appropriate biomarkers seems to be of paramount importance for directing therapy and for better understanding the immune response in TB. The transcriptomic studies presented suggest the importance of a neutrophil-driven interferon (IFN)inducible gene profile in specifically signalling TB progressors versus bearers of other lung pathologies [4]. Indeed, identification of progressors (about 10% of the TB-infected population) by gene expression profiles and correlating those with host response to vaccination with BCG, after exposure to M. tuberculosis, can give us hints about the efficacy of our intervention, as was shown by Willem Hanekom in his lesson, and later by January Weiner in his mathematical model. Elena Levashina opened the malaria session presenting detailed studies on the molecular mechanisms by which the Plasmodium evades the mosquito immune system, to cope with a changing environment for the success of the infection in both the human host and mosquito vector. Understanding the principal molecular mechanisms of Plasmodium life cycle will allow us to envision three major targets for malaria vaccine, as shown in Kai Matuschewski’s presentation [5]. Inhibitory antibodies against antigenic determinants on extracellular invasive stages of the parasite, inhibitoryantibodies against parasite-encoded
www.eji-journal.eu
1573
1574
FORUM
Eur. J. Immunol. 2014. 44: 1573–1574
Figure 1. EFIS-EJI Ruggero Ceppellini Advanced School of Immunology participants.
adhesion molecules on the erythrocytes membrane and parasite-specific T lymphocytes directed to parasite-invaded liver cells are the promising candidates for malaria vaccines. These concepts were further developed in Ripley Ballou’s lecture, which was especially focused on the most advanced pre-erythrocytic stage vaccine candidate, RTS S/AS01, that is an adjuvant particle-based vaccine that targets the circumsporozoite protein (CS) that covers the surface of Plasmodium sporozoites, inducing high levels of antibodies and a strong CD4+ T-cell effector response. Marita Troye-Blomberg suggested that boosting the innate immunity can be an alternative to the specific targeting of the adaptive immune response for vaccine development, She showed that the effect of CS vaccination was potentiated using BCG as an adjuvant. The need to
include a strong innate immunity boost in the construction of effective vaccines was also subsequently stressed by Ali Harandi in his lesson, which attributed particular priority to the mucosal route as a portal of pathogen entry. T-cell reactive clones can also be profitably used to increase our understanding of the immune response to pathogen infection and, as Federica Sallusto said in her presentation, T-cell library technology can guide us in the design of effective vaccines [6]. B-cell impaired function during early infection might be involved in the lack of responses to vaccination in patients with HIV, accounting for the important role played by these cells in HIV vaccine development, as underlined by the lecture of Francesca Chiodi [7], the co-Director of this course. The course was closed by the lecture of Mark Cotton on studies of Isoniazid Prevention Therapy
(IPT) in children affected by both TB and HIV. In 22 years of Ceppellini School courses, the relaxed interaction between teaching staff and the audience was at its best in this course, especially because of the closeness of the two parties sharing the same location throughout the entire event, with informal round tables and smaller working groups that promoted a vast array of questions and answers, from immunology to the clinics. The large participation of highly motivated young scientists and MDs from developing countries — especially from Africa thanks to the generosity of the Bill & Melinda Gates Foundation — was also a great asset in the success of this event. The spectacular view of majestic, sleeping Vesuvius completed the collective satisfaction. Antonio Di Giacomo Member, Board of Directors EFIS-EJI Ceppellini Advanced School of Immunology
Selected References 1 Di Giacomo, A., Eur. J. Immunol., 2013. 43: 13–14. 2 Kaufmann, S. H. E., Haus Publishing, 2009. 3 Ndung’u, T. and Weiss, R. A., AIDS 2012. 26: 1255–1260. 4 Berry, M. P. R. et al., Nature 2004. 466: 973–77. 5 Hafalla, J. C. et al., Immun. Rev. 2011. 240: 297– 316. 6 Sallusto, F. and Lanzavecchia, Eur.J.Immunol. 2009. 39: 2076–2082.
A.,
7 Cagigi, A. et al., Lancet Infect. Dis. 2010. 10: 499– 503.
Up-coming EFIS-EJI Ceppellini Advanced Course “The Maternal Immune System in Pregnancy” Course Directors: Francesco Colucci & Ashley Moffett (Kings College, Cambridge, UK) Near Naples (Italy) 6 – 9 December 2014
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eji-journal.eu
Eur. J. Immunol. 2014. 44: 1573–1574
News & EFIS The EFIS-EJI Ruggero Ceppellini Advanced School of Immunology Malaria, Tuberculosis and HIV/AIDS: Novel vaccination strategies against the three major killers
Novel and innovative vaccines against the three most deadly infectious diseases (Malaria, Tuberculosis (TB) and HIV/AIDS) are being investigated around the world, both in leading research laboratories and in clinical trials. For the past 22 years, the EFIS-EJI Ceppellini School (www.ceppellini.it) has focused on topical aspects of immunology [1], and the 2013 course focused on these deadly diseases under the direction of Stefan H.E. Kaufmann (Max Planck Institute, Berlin) and Francesca Chiodi (Karolinska Institute, Stockholm). This meeting was held in the shadow of the volcano Vesuvius (Castellammare di Stabia) the 16–20 October 2013 (Fig. 1). The aim of this course was to spread the newest advancements in the field among scientists and health operators, especially those coming from developing countries, where the mortality for such diseases reaches the highest peaks. Vaccines represent the best tool to prevent infectious diseases, as proven by those against polio, smallpox, measles, mumps, rubella, hepatitis B, diphtheria, tetanus, pneumococcal pneumonia, and meningococcus. There is founded hope that in the very near future novel vaccines will be developed to fight also malaria, tuberculosis and HIV/AIDS, although 100% protection from all three diseases seems an overly ambitious goal, since other factors must be taken into account, such as poverty and malnutrition.
Understanding the mechanisms by which those pathogens evade the body’s immune response is of course of crucial importance in developing strategies to construct novel vaccines. The course focused on various aspects of the pathophysiology of infection, especially on the immune regulation at host-infectious agent interface. As underlined by director Stefan Kaufmann [2], some vaccines already exist, but are not universally effective, i.e. for bacille Calmette-Gu´erin (BCG) that only protects newborns from severe forms of disseminated TB but fails to prevent the most prevalent form, pulmonary TB, in all age groups. A recent vaccine for AIDS, using RV144, didn’t show satisfactory protection, whereas RTS vaccine for malaria offers some but not complete protection. Therefore, a careful comparison of host responses and markers of disease progression or regression in protected versus non-protected individuals is necessary. Rino Rappuoli told the audience of the great improvements in vaccine technology, the so-called third wave of vaccine development, characterized by optimal design antigens, adjuvants and delivery systems, derived from the new acquisitions on the structure of the antigens and epitopes and their interaction with the human immune system. As emerged in later discussions, these exciting and very promising advancements in vaccine making technology clash against the difficulty of delivering even existing solutions to resource-limited settings, i.e. third world countries, compelling us to find ways to accelerate a more efficient and less costly decision making process in selecting new vaccine candidates. The HIV/AIDS session was opened by the lecture of Robin Weiss, who shared his vast experience and wisdom in the field, discussing the successes and failures of the last 30 years of HIV science
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
[3]. This was followed by the presentation of Thumbi Ndung’u, that focused on the study of CD8+ T cells and Gag-protease interactions in HIV-1-infected individuals in South Africa, showing that an intricate balance between those cells and viral fitness is required for HIV-1 immune control. Opening the TB session, Anne O’Garra presented the problem of the diagnostic recognition of individuals who would progress in the disease, for which there are no tests available. Identifying appropriate biomarkers seems to be of paramount importance for directing therapy and for better understanding the immune response in TB. The transcriptomic studies presented suggest the importance of a neutrophil-driven interferon (IFN)inducible gene profile in specifically signalling TB progressors versus bearers of other lung pathologies [4]. Indeed, identification of progressors (about 10% of the TB-infected population) by gene expression profiles and correlating those with host response to vaccination with BCG, after exposure to M. tuberculosis, can give us hints about the efficacy of our intervention, as was shown by Willem Hanekom in his lesson, and later by January Weiner in his mathematical model. Elena Levashina opened the malaria session presenting detailed studies on the molecular mechanisms by which the Plasmodium evades the mosquito immune system, to cope with a changing environment for the success of the infection in both the human host and mosquito vector. Understanding the principal molecular mechanisms of Plasmodium life cycle will allow us to envision three major targets for malaria vaccine, as shown in Kai Matuschewski’s presentation [5]. Inhibitory antibodies against antigenic determinants on extracellular invasive stages of the parasite, inhibitoryantibodies against parasite-encoded
www.eji-journal.eu
1573
1574
FORUM
Eur. J. Immunol. 2014. 44: 1573–1574
Figure 1. EFIS-EJI Ruggero Ceppellini Advanced School of Immunology participants.
adhesion molecules on the erythrocytes membrane and parasite-specific T lymphocytes directed to parasite-invaded liver cells are the promising candidates for malaria vaccines. These concepts were further developed in Ripley Ballou’s lecture, which was especially focused on the most advanced pre-erythrocytic stage vaccine candidate, RTS S/AS01, that is an adjuvant particle-based vaccine that targets the circumsporozoite protein (CS) that covers the surface of Plasmodium sporozoites, inducing high levels of antibodies and a strong CD4+ T-cell effector response. Marita Troye-Blomberg suggested that boosting the innate immunity can be an alternative to the specific targeting of the adaptive immune response for vaccine development, She showed that the effect of CS vaccination was potentiated using BCG as an adjuvant. The need to
include a strong innate immunity boost in the construction of effective vaccines was also subsequently stressed by Ali Harandi in his lesson, which attributed particular priority to the mucosal route as a portal of pathogen entry. T-cell reactive clones can also be profitably used to increase our understanding of the immune response to pathogen infection and, as Federica Sallusto said in her presentation, T-cell library technology can guide us in the design of effective vaccines [6]. B-cell impaired function during early infection might be involved in the lack of responses to vaccination in patients with HIV, accounting for the important role played by these cells in HIV vaccine development, as underlined by the lecture of Francesca Chiodi [7], the co-Director of this course. The course was closed by the lecture of Mark Cotton on studies of Isoniazid Prevention Therapy
(IPT) in children affected by both TB and HIV. In 22 years of Ceppellini School courses, the relaxed interaction between teaching staff and the audience was at its best in this course, especially because of the closeness of the two parties sharing the same location throughout the entire event, with informal round tables and smaller working groups that promoted a vast array of questions and answers, from immunology to the clinics. The large participation of highly motivated young scientists and MDs from developing countries — especially from Africa thanks to the generosity of the Bill & Melinda Gates Foundation — was also a great asset in the success of this event. The spectacular view of majestic, sleeping Vesuvius completed the collective satisfaction. Antonio Di Giacomo Member, Board of Directors EFIS-EJI Ceppellini Advanced School of Immunology
Selected References 1 Di Giacomo, A., Eur. J. Immunol., 2013. 43: 13–14. 2 Kaufmann, S. H. E., Haus Publishing, 2009. 3 Ndung’u, T. and Weiss, R. A., AIDS 2012. 26: 1255–1260. 4 Berry, M. P. R. et al., Nature 2004. 466: 973–77. 5 Hafalla, J. C. et al., Immun. Rev. 2011. 240: 297– 316. 6 Sallusto, F. and Lanzavecchia, Eur.J.Immunol. 2009. 39: 2076–2082.
A.,
7 Cagigi, A. et al., Lancet Infect. Dis. 2010. 10: 499– 503.
Up-coming EFIS-EJI Ceppellini Advanced Course “The Maternal Immune System in Pregnancy” Course Directors: Francesco Colucci & Ashley Moffett (Kings College, Cambridge, UK) Near Naples (Italy) 6 – 9 December 2014
C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eji-journal.eu
