this quarterly edition of our newsletters is dedicated to the report of one of the activities regularly sponsored by our Society, i.e. the Summer School on Innovative Approaches for Identification of Antiviral Agents (IAAASS), that took place in Sardinia last October, by the technological Centre of the University of Cagliari, at Santa Margherita di Pula, and is also covering the theme of innovative vaccines and vaccination in Europe.
The IAAAS, as usual, was well attended by students and researchers from all over the world and Professor Tramontanois herewith producinga short review on the major research lines that were highlighted at the School. In particular, the multidisciplinary approach to new antivirals development that foresee a synergistic interaction between Virology, Pharmacology, Cellular and Molecular Biology, Structural Biology, Systems Biology, Organic, Physical- and Medicinal Chemistry with the aid of in silico computer modeling and thermodynamics.
The other two subjects of this newsletter, reported by Dr. Sebastian Ulbert and Professor Roberto Burioni, deal with vaccinology and vaccine practices, an area heavily involving science, and Virology in particular, but of great interest for its repercussions on Public Health organization in Europe and on the new threats we are continuously facing from (re)-emerging epidemics. Suffices to mention the recent outbreaks of MERS-Coronavirus in the Middle East, Ebolavirus in West Africa, Crimean-Congo Hemorrhagic fever virus in Spain, Yellow fever in Angola, not to forget about the re-emergence of poliovirus and dyphteria very close to us. A great need is felt about a stronger interaction between the vaccine Industry (highly concentrated in Europe) and Academia, especially to face unresolved problems like vaccines against AIDS, dengue fever, tuberculosis, malaria, just to quote the biggest killers and most debilitating causes of morbidity among infectious diseases. It is my personal opinion that the EU organization should invest more resources to finance basic studies dedicated to this field; this would also prompt more young investigators to cultivate the science of the invisible world, made largely of bacteria, fungi, protozoa and viruses, that constitute the largest part of the biosphere of our planet. A not negligible issue is the long pursued idea of harmonizing vaccine practices in Europe, a duty nowadays left to the care of single Nations or even of single Regions. It is in fact evident, as reported by Burioni, that some vaccinations are obligatory or highly recommended in some parts of Europe but not in others. This is clearly conflicting with the desirable free circulation of citizens within Europe and with the lack of control on the vaccination status of the immigrant population. Moreover, there is a large discrepancy about the vaccination calendar throughout European Countries and this is not an example of a proper coverage and prevention measure. The long sought agreement about a unified European procurement, that could serve all Nations in time and represent a guarantee of getting vaccines at convenient prices from Manufacturers, seem to have lost ground when considering the fact that single Regions are purchasing directly from Pharma.
In conclusion, there are many unresolved questions and issues that need to be debated and properly addressed, for which ESV, through its numerous experts in the field, could have a unified voice at the level of European Institutions where sanitary and scientific decisions are taken (like ECDC, EC Directorates such as, e.g., those for Research and Innovation and Health and Food Safety).
President of the European Society for Virology
Report on 3rd Summer School on Innovative Approaches for Identification of Antiviral Agents
Enzo Tramontano, University of Cagliari, Monserrato (Cagliari), Italy
With the ESV support, the third Summer School on Innovative Approaches for Identification of Antiviral Agents took placefrom September 28th to October 2nd, 2016 at the Sardegna Ricerche Research Park in Santa Margherita di Pula, Sardinia, Italy. IAAASS was organized for the first time in September, 2012 by Enzo Tramontano and Elias Maccioni of the Universities of Cagliari (Italy), Cristina Parolin of the University of Padova (Italy), Stuart Le Grice, of National Cancer Institute, Frederick (USA), and Katarzyna Purzycka, of the Polish Academy of Sciences, Lublin (Poland).
Eighteen senior scientists (among which Giorgio Palù, Thomas Mertens, Graciela Andrei, Mike Bray, José Esté and Anna Papa) and 48 graduate students and postdoctoral fellows, mostly Europeans but also from Asia and Americas, attended the third IAAASS. Each day the program was tightly organized in i) 4 morning plenary lectures by senior researchers who are leading scientists in the fields of virology, biochemistry, molecular modeling, crystallography and medicinal chemistry; ii) in the afternoon, student poster and oral presentations and iii) in early evening, small discussion groups among faculties and students: in these informal groups students had the opportunity to ask questions and put forward their own ideas, and in return senior researchers offered advice, based on their own experience.
Giorgio Palù of University of Padova (Italy) provided an overview of current research on Zika virus. Thomas Mertens of Ulm University (Germany) showed that how prevention of viral disease can be obtained through the elicitation of immune responses. Graciela Andrei of the Rega Institute in Leuven (Belgium) talked of challenges and opportunities of Herpes virus drug resistance. Mike Bray, editor-in-chief of Antiviral Research, reviewed the wide variety of viruses that are maintained through circulation in animals, but can cause disease in humans.
José José of the Fundacia Irsicaixa, Barcelona (Spain) presented new therapeutic strategies targeted to sensing of HIV-1 infection.Anna Papa of Aristotle University in Thessaloniki (Greece) reviewed emerging viral infections in the Mediterranean region, most of which are transmitted by the bite of mosquitoes or ticks.
Overall, interactions among students and older scientists was the very key aspect of the IAAASS, as it stimulated interests by providing the chance of sharing both scientific ideas and personal experiences among scientists vividly sharing a passion for science. In a questionnaire provided at the end of the meeting, > 80% of students stated that the IAAASS had met their primary objectives, and nearly all said it would influence their future work. Around 40% said that they had been attracted to the event principally by the opportunity for networking, and the rest had chosen it because of the overall agenda and list of speakers. Two-thirds rated the relevance of presentation topics “excellent,” while 50% found the group discussions “excellent” and 40% “very good.”
Overall, this ESV initiative achieved the criteria for successful mentoring: a combination of critical review of the scientific literature, sharing of ideas and discussion of new paradigms for research that led to an excellent blend to support the education of the next generation virologists. The Forth IAAASS is scheduled to take place in September 2018.
Flavivirus Vaccines – Why Not Simply Copy-Paste?
Sebastian Ulbert, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany
The family flaviviridae includes important human pathogens such as yellow fever (YFV), dengue (DENV), Japanese encephalitis (JEV), tick borne encephalitis (TBEV), West Nile (WNV) and Zika (ZIKV) viruses. All these pathogens are transmitted by arthropod vectors and cause disease symptoms that range from flu-like to severe hemorrhagic fever or even neurological complications. Recently, links between ZIKV-infection and fetal malformation have been documented. Flaviviruses are present in almost all tropical areas in the world, and increasing numbers of subtropical countries become endemic e.g. for WNV or DENV. Others (TBEV) are circulating in moderate areas such as Central and Northern Europe. In general, factors including climate change and increasing human and animal mobility support the worldwide spread of flaviviruses.
The development of methods to protect from flavivirus infections has started over 80 years ago when the YFV-vaccine was generated. This vaccine, consisting of an attenuated version of the virus, is still used today and is one of the greatest success stories in the combat against infectious diseases. It has dramatically reduced the number of YF cases worldwide by providing a robust and lifelong immunity.
In addition to YFV, vaccines have been licensed for TBEV, JEV, DENV (very recently in some countries) and WNV (in veterinary medicine). They all are effective in preventing disease, although they rely on different technologies, namely inactivated viruses, attenuated viruses or chimeric attenuated viruses by inserting e.g. DENV envelope proteins into the YFV vaccine virus.
The fact that swapping envelope proteins is tolerated by flaviviruses underlines the structural similarity within this family. Likewise, over two decades of research have revealed important common principles for the protective immune response against flaviviruses: individuals surviving an infection have acquired a lifelong immunity, and protection mainly relies on neutralizing antibodies which target specific domains in the structural proteins, most importantly in the envelope protein. A large number of pre-clinical and early clinical studies have shown that this antigen is sufficient to mediate protection against virtually every flavivirus analyzed so far, regardless whether it is applied as e.g. recombinant protein, DNA-plasmid or part of a virus-like particle or a viral vector.
In light of these results, the development of potent vaccines for the remaining flaviviruses should not be too difficult, and the existing technologies should be rapidly applicable to fight emerging threats such as ZIKV. However, the situation is not as easy and, unfortunately, there are several factors that prevent a straight-forward vaccine-based eradication of flavivirus-caused disease. In contrast to the common principles in immunological protection, these factors are specific to each individual flavivirus and need to be resolved accordingly:
DENV is circulating in four serotypes, but immunity to the virus is serotype-specific. Moreover, a secondary infection with another serotype might even cause severe disease, a phenomenon potentially explained by low affinity antibodies that bind to the virus and thereby enhance its entry into target cells. As a consequence, a DENV vaccine has to be equally protective against all four serotypes from the first immunization onwards. Moreover, pre-existing antibodies might influence the protection against one or more serotypes. These issues have represented major challenges in recent efficacy trials and were not always resolved. Based on results from a phase 3 clinical trial, the DENV vaccine recently approved in some countries is to be used only in individuals over 9 years of age, hence solutions for younger children (which are at highest risk for severe dengue) still have to be found.
For a human WNV vaccine several candidates have been developed and successfully passed initial clinical trials. Interference of immune responses to other flaviviruses or vaccines is not expected. However, given the sporadic and unpredictable nature of WNV outbreaks, efficacy trials are difficult to plan, and the (currently) relatively low case numbers with severe symptoms apparently do not represent a very attractive market for the vaccine industry, at least in Europe. In addition, mostly the elderly are at risk for severe symptoms, hence vaccine development has to meet a target population with an aged immune system. Research to address these challenges needs funding, and European funding agencies should not disregard WNV when e.g. investing millions into ZIKV work.
Due to the current epidemic in South America and the potential further spread, ZIKV-vaccine research has started at full speed. During the last year most if not all vaccine-platforms that are effective against other flaviviruses have been adapted to ZIKV. Results show that ZIKV is not an exception among flaviviruses, and a protective immune response can be elicited by a large variety of vaccine technologies delivering the envelope protein. But the path towards a ZIKV vaccine is not without obstacles, either: ZIKV- and DENV-endemic areas overlap, and data obtained by several groups imply that antibodies against DENV might enhance infection with ZIKV and vice versa. This is of course a major concern for vaccines and studies have to be performed in order to address this issue. These have to include the analysis of immune responses in persons infected with both viruses or vaccinated against DENV and infected with ZIKV. Should an interference of primary infections or vaccination indeed be found, a possible solution would be a single vaccine for all serotypes of DENV plus ZIKV. However, in light of the difficulties to generate an efficient vaccine for DENV alone, such a technology would probably still need years of pre-clinical and clinical research.
Taken together, there are efficient vaccines available to protect from some, but not all flaviviruses. Despite the enormous amount of knowledge gained durint the past decades, several difficulties still remain before effective immunization strategies are available to successfully complete the fight against flavivirus infections.
Vaccinations in Europe: Need of Harmonization in Strategies and Procedures
Roberto Burioni, Università Vita e Salute, Faculty of Medicine, San Raffaele Hospital, Milan, Italy
European Union puts a great effort in standardization for promoting the easy circulation of goods in a free common market. Strict regulations are dictating the standards for the production of cableway installations designed to carry persons, explosives for civil uses, hot-water boilers, pyrotechnics and even pressure vessels. Beside free circulation of goods, another cornerstone of the European Union is the free circulation of citizen, allowed to travel between nations freely and without any border control. From the medical point of view it is obvious that individuals can carry with them infectious agents, and considering that vaccination is a social measure, differences in vaccination strategies and coverage between countries can be relevant for infection control. Unfortunately, European Union countries have different vaccination schedules and policies making difficult to catch up with vaccinations when a toddler is moving with his family from one European country to another.
Let’s have a quick look to different vaccine schedules available on the dedicated web page of the European Centre for Disease Prevention and Control (ECDC) (http://vaccine-schedule.ecdc.europa.eu/pages/scheduler.aspx). For example, if we consider anti-tetanus vaccine it is evident that most of the European countries recommend three monthly administrations starting at two months of life followed by a boost at approximately one year of age. However, some countries (i.e. Austria, Denmark, Finland, Italy, Norway, Sweden) start vaccinating during the third month of life, with a second administration in the fifth month and a final boost of approximately one-year-old children. What about if an Italian or a Danish family with a 4-month-old child move to Germany?
If that is true for Europe-wide recommended vaccinations, such as that against tetanus, the situation is inevitably and markedly more complex for “newer” vaccinations. That is, for example, the case of the anti-meningoccosus C vaccine. If we go through the comparative schedule on the website, it will be easy to evidence that only half of the reported countries include it within its own national schedule. The sometimes even striking differences in timing are – somehow – venial sins. What about if an Italian family, who could have a child vaccinated against MenC in Italy, moves to Denmark where this vaccination is not recommended?
As a conclusion, Europe is putting a great deal for preserving the integrity of the Euro currency that an European Citizen is carrying in his pockets. The same effort should be devoted to uniform vaccination schedules and policies for the most effective prevention of dangerous infectious pathogens that are still at large.
News and Updates
Election to the Advisory Council 2016
During the 4th General Assembly in Hamburg on October 21, 2016, the following 12 representatives of the Advisory Council of the European Society for Virology were elected for the next term of office 2016-2019 (in alphabetical order):
- Albert Bosch, Department of Microbiology, University of Barcelona, Spain
- Margarita Del Val, Centro de Biología Molecular Severo Ochoa, Universidad Autònoma de Madrid, Campus de Cantoblanco, Spain
- W. Paul Duprex, Cell and Tissue Imaging Core, Dept. of Microbiology, Boston University School of Medicine, USA
- Urs Greber, Institute of Molecular Life Sciences, University of Zurich, Switzerland
- Michael Kann, UMR-CNRS 5234, University of Bordeaux 2, France
- Marion Koopmans, Erasmus MC Rotterdam, The Netherlands
- Thomas Mettenleiter, Department of Molecular Biology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Germany
- Albert Osterhaus, Department of Virology, Erasmus MC, The Netherlands
- Lennart Svensson, Div. of Molecular Virology, Med. Faculty, University of Linköping, Sweden
- Jan Svoboda, Dept. of Viral and Cellular Genetics, Institute of Molecular Genetics, Czech Republic
- Veronika von Messling, Paul-Ehrlich-Institut, Langen, Germany
- Friedemann Weber, Institute for Virology, FB10 – Veterinary Medicine, Gießen, Germany
Election to President 2016
During the 4th General Assembly in Hamburg on October 21, 2016, Giorgio Palù, Department of Molecular Medicine, School of Medicine, University of Padua, Italy, was elected to President of the European Society for Virology for the next term of office 2016-2019.
Election to the Executive Board 2016
The First Vice President, Second Vice President, Secretary General and Treasurer of the European Society for Virology were elected for the next term of office 2016-2019 during the 4th General Assembly in Hamburg on October 21, 2016, as well:
- Ben Berkhout, Academic Medical Center of the University of Amsterdam, the Netherlands, was elected to First Vice President.
- Noël Tordo, Instituts Pasteur, Paris-France, Conakry Guinee, was elected to Second Vice President.
- Dana Wolf, Hadassah Hebrew University Medical Center, Jerusalem, Israel, was elected to
- Thomas Mertens, Institute for Virology, University Hospital Ulm, Germany, was elected to
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27th Annual Meeting of the German Society for Virology
22 – 25 March, 2017
20th International Workshop on Kaposi’s Sarcoma Herpes Virus (KSHV) and Related Agents
25 – 28 July, 2017
42nd FEBS Congress
10 – 14 September, 2017
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