sou · GXB355 · 2009-06-10 00:00:00 — We believe that it will increase the research potential of the register to place it in a research institution like SMI. With all new vaccines, there is a small risk that a rare side effect has not been detected in pre-marketing trials. Only the use in tens and hundreds of thousands of children can reveal such side effects. Monitoring of these is and should probably remain the responsibi- lity of the . Monitoring of public perception Vaccines scares, such as the one in the UK concerning MMR vaccine and autism, can seriously undermine the vaccination pro- gramme and lead to rapidly diminishing vaccination coverage. The changes may also come more slowly with the population gradually loosing confidence in vaccination. We believe that some kind of monitoring of public perception is necessary to support a vaccina- tion programme. Some of this may be seen more as social science research, but could easily be regarded as a task for . Surveillance of vaccination effects The first measurable effect of a vaccination programme is that the vaccinees become immune against the disease. For many diseases and vaccinations, immunity may easily be measured in a blood or sample. By measuring the immune status (seroprevalence) in segments of the population, it is possible to follow the duration of protection offered by vaccination and thus the needs for revaccina- tion. These data are also very useful for infectious disease model- ling to predict the risk of future disease outbreaks. We have noted that SMI perform immune status surveys with ten years interval, which we consider is too seldom. Secondly, surveillance of disease gives of course a measure of the ultimate effect of the vaccination programme. Repeated evalu- ation and improvement of the surveillance system may be needed to give reliable disease incidence figures. This is especially true when the disease is near elimination and many doctors will not recognise the disease, such as with measles. With the SmiNet, has a modern disease surveillance system. SMI may, however, have to evaluate the disease surveillance system more often. Thirdly, strain surveillance is becoming increasingly important when strain-specific vaccines are introduced. For instance, the new conjugate childhood vaccines against invasive pneumococcal disease protects only against pneumococci belonging to a few fre- quently occurring of the more than 80 of pneumococcal serotypes. Only by monitoring the serotype distribution among disease cases is it possible to predict the impact of vaccination and to measure the actual effect, including an effect where other serotypes just replaces those which vaccination protects against. We were surpri- sed to learn that SMI only recently started a systematic collection and serotyping of pneumococcal bacteria from patients with inva- sive disease. This information could then be merged with the case information in SmiNet. In other Nordic countries, this has been going on for many years and has provided an excellent starting point for surveillance and research linked to the pneumococcal vac- cine introduction. Finally, for some vaccination programmes there may be a need to perform special studies, so-called phase IV studies of vaccination effectiveness. An important design is the case-control study where the vaccination history of cases is compared to the vaccination history of other children. This kind of research is easily done when there is both a good disease surveillance system (such as SmiNet) and a vaccination register in place. We would have liked to see more of this kind of research. Laboratory research in immune mechanisms, diagnostic methods, vaccine composition and other issues are well developed at SMI (see chapter 3 and others). Such research may give the staff confi- dence in their role as advisor to Swedish health authorities con- cerning the vaccination programme, for instance when it comes to a choice of vaccination regimens. We do not, however, believe that it is necessary for the institute to develop or produce its own vac- cines in order for it to be a good advisor to the health authorities concerning the vaccination programme. Conclusion regarding vaccination related research There is large potential for an overarching vaccination related research and surveillance portfolio at SMI to support the national vaccination programme. The activities could lead to improved coll- laborations between departments. We recommend creating a hori- zontal coordination mechanism for vaccination-related research and surveillance inside SMI. 6.3Department of Immunology and vaccinations The section of HIV vaccines, led by and employing eminent senior scientists such as G. , has a long and successful history in the development of new vaccines (HIV) ranging from basic molecular biology and immunological work to field trials. The researchers are also employed in public health interventions such as prevention of mother-to-child trans- mission of HIV during breast feeding period using short term anti- retroviral treatment. The research has received considerable inter- national recognition in scientific as well as in funding decisions. The topics include: Analysis of the natural course of HIV infection in a cohort with no antiretroviral treatment or treatment of opportunistic infec- tions, leading to characterisation of clinical and immunological parameters which can be applied universally, Studies on pathogenesis in SIV-infected primates. Important findings include the role of co-recptors in the pathogenesis and loss of memory B-cells during the course of infection. Studies supporting the development of vaccines include topics such as DNA-antibodies, IgA neutralizing capacity, induction of mucosal immunity, studies on induction and function of dendritic cells, production of anti-viral factors by CD8 cells, evaluation of the role of neutralizing antibodies in primate mo- dels and cloning of HIV-2 gp-125 and its expression. Studies with new vaccine candidates, of which the combination of DNA priming and rMVA has proven very immunogenic in animals and human volunteers and is now waiting results from wider clinical trials. studies concerning the prevention of mother-to-child transmission by proper antiretroviral regimen. Several evaluation studies of various HIV-related laboratory test applications. The work has strong roots in collaboration within and this has made several of the above-mentioned studies possible. Another important asset in particular for vaccine development has been the availability of primates allowing detail studies in the immune re- sponse and protection mechanisms. All these works have conside- rable international importance and their relevance may be bigger globally than strictly from Swedish viewpoint today. National and international impact of the research is excellent (5), focusing, relevance: 5, quality and quantity: 5. Section of Translational and Clinical immunology headed by . The head of the section has been recently recruited, therefore some projects are in their early phases. Research related to tuberculosis vaccine development is of particu- lar interest. Methodological strengths include peptide microarray and other similar technologies that are used for detailed studies about immune response. Also non-human primates have been used successfully. Mapping of possible epitopes for tuberculosis vacci- nes seems a work with high potential value for the future. Another group, led by Hans Gaines has studied cytokine re- sponses and developed and refined clinical application based on them. These works are linked with a.o. HIV vaccine studies. An epidemiological study about transmission of tuberculosis among immigrant school children has been reported. National and international impact of the research is good (4), focusing, relevance:4, quality and quantity: 3. Section for vaccine research, (headed by ). and his group have a long and successful career in stu- dies covering various aspects of molecular biology of alpha-viruses. That basis has been used in many ways for important applications that have led to scientific breakthroughs reported in top journals (Science, Nature, etc). The work has increased our understanding of the molecular mechanisms of antigen expression and presenta- tion and their roles in the immune response. Their observations have been important also for the new developments in HIV and Malaria vaccine research. Often, the works are the result of colla- boration with groups in other universities of in other countries and the section has had an important role in the coordination of several large network projects. Since much of the work is of very basic character, rapid applications with high national impact could not and should not be expected. National and international impact of the research is excellent (5), focusing, relevance: 5, quality and quantity: 5. Of interest are also the observations and experimental applica- tions concerning the development of a vaccine against HCV. Work is also ongoing to evaluate and establish a new and impro- ved test for tuberculosis. The work is also extended to Belarussia where the high prevalence and incidence makes certain evaluation and application studies more feasible than if they were performed in . Section for the vaccine programme (, , , ). Pertussis is an im- portant communicable disease because the previous vaccinations did not give a good protection. In addition, halted the ge- neral childhood pertussis vaccinations for several years opening an unusual window of opportunity for epidemiological research. The group led by has responded to this with a productive way producing several important reports covering the analysis of the properties and long-term follow up of newer vaccines, follow- up of epidemiology of Bordetella pertussis spread using molecular techniques and evalulating optimal methods for diagnostics. The section is involved in an evaluation study using live atte- nuated bordetella vaccine that is going on as a international multi- center consortium project. Another multicenter study tests the use of allogenic HIV mucosal vaccine on macaques and a related pro- ject testing the potential of a construct of MHC antigens with adjuvant and extracellular receptor molecule for creating microbi- cidal and preventive immunity. The scientific potential of these studies is quite remarkable, the results will contribute to the pro- gress of the relevant research. National and international impact of the research is good (4), focusing, relevance: 4, quality and quantity: 4. Evaluation of the clinical efficacy of varicella-MMR vaccine pre- parates and a project aimed at influencing the attitudes towards vaccinations through training are among the more traditional activities of a vaccinology department. The work in the department matches and even exceeds the level and volume in the institutes in the Nordic countries. Its rele- vance to the Swedish society is good. 6.4Center for Microbiological preparedness (för Mikrobiologisk Beredskap) covers bacteriology and virology. Concerning the bacteriology, the research is represented by professor , and . The major area of their bacteriology research is environ- mental amoebae (Acanthamoebae) and their interaction with vari- ous bacterial pathogens like for instance Vibrio, Aeromonas and The relevance of this area is the possibi- lities of amoebae to train bacteria for intercellular growth with ob- vious pathogenetic aspects. The department also focus on research of the epidemiology of outbreak of enteric pathogens, and impor- tantly also of use of rapid sequencing for identification of patho- gens used for bioterrorism such as Francisella tularensis or Bacillus anthracis. The quality of the research, especially on the amoebae/bacteria interaction and rapid detection of bioterror bac- teria, is of international level and the relevance is high concerning detection of outbreaks in . National and international impact: 3–4, focusing, relevance: 3–4, quality and quantity: 3–4 especially of the amoebae/bacteria inter- action research. In conclusion, the research and knowledge to their field of ex- pertise is on an international level, equally to what is found in comparable institutions in other Scandinavian countries, and it very well match the demands of the Swedish society. Section of virology. (, , , and others). Projects dealing with Hemorrhagic Fever Virus (CCHFV) combine high level molecular biology with an important pathogen, not only from the epidemiological point of view but also from the potential for harmful use of the virus. Works dealing with various factors in the pathogenesis are important and represent a leading role also internationally. Works employing specific inhibitory effects by NO to CCHFV and SarsCoV are important and demonstrate high standard of biological and virological research. National and international impact: 5, focusing, relevance: 5, quality and quantity: 5. Hantavirus studies have demonstrated the public health impor- tance of this virus group in the Nordic countries. Several valuable studies have been reported describing the epidemiology, pathology and pathogenesis. Studies cover demonstration of sex difference in the interleukin production induced by the virus, molecular mecha- nisms of pathogenesis and cell death, salivary excretion of the virus in humans and even reveal a new mechanism of interference with innate immunity which may be relevant for other dangerous viruses also. In the ex-vivo stability works the group has utilized the access to P-4 laboratory environment in a good way. National and international impact: 5, focusing, relevance: 5, quality and quantity: 5. Gastrointestinal-viruses: The laboratory has been actively invol- ved in several European collaborative studies which have mapped the molecular epidemiology of noroviruses. It has also contributed to the analysis and description of several outbreaks originating in and developed a novel simple diagnostic test in collabora- tion with . The scientific importance is not matching the CCHFV works but the public health importance is considerable. Also, international collaboration is unusually important within this particular field. National and international impact: 3, focusing, relevance: 4, quality and quantity: 4. The main task for the center is to provide expert help in the idenfication of and response to dangerous emerging or imported viruses which are not covered by more routine diagnostics and surveillance. This requires good competence to rapidly develop or apply new diagnostic methods and molecular surveillance to such viral diseases. The availability of BSL-4 facility allows handling of even the most dangerous pathogenic viruses and as such it provides a very important resource not only to and SMI but also to other Nordic countries and EU. The laboratory also has a trans- mission electron microscope in duty to identify highly pathogenic viruses, a resource that is available in fewer and fewer institutes today. The research in the center is of high quality matching the research in the other Nordic institutes. The availability of BSL-4 facility, the only one in the Nordic countries, puts it into a special place what comes to national and international relevance. 6.5Department of Parasitology, mycology, water and environment , Mycology and Environmental Microbiology is headed by and the professor is . This section has a comprehensive research on especially parasitology and notable malaria where the scientific performance is quite impressive and on very high international level. The research in this area covers molecular biology, pathoge- nesis and even vaccines. The research in other parasites comprise toxoplasmosis, Giardia, Cryptosporidia and Entamoebae histoly- tica and a few other topics such as resistance in head lice in , and also here the research is of a very good quality. the section has adequate research on different fungus infections including pneumocystis and candida, and a rather comprehensive research on a high international level in microbial problems (inclu- ding outbreak investigations, desinfection, laboratory equipment) concerning drinking and waste water. Like other departments the international research network is comprehensive and so are the sources of funding of the research. National and international impact: 4–5, focusing relevance: 4–5, quality and quantity: 4–5 of malaria research and toxoplasmosis research. In conclusion, the research and knowledge to their field of expertise is on a high international level, equally to what is found in comparable institutions in other Scandinavian countries, and it very well match the demands of the Swedish society. Several of the projects that are listed under the department of Virology are collaborative works that are also reported by others. The head of the department, , has been an important investigator in most of the HIV-studies reported by the department of Immunology and vaccinations. They include, among others, clinical and diagnostic studies on the open cohort in , evaluation of diagnostic strategies for HIV-1, HIV-2 and HTLV, studies on immune responses and coinfections and impor- tant information about the public health impact of the infections in a antiretroviral-naïve population. They are of considerable value to the overall development of HIV research in the institute. The scientific value, relevance and value to SMI are good-to excellent. An interesting sideline deals with development of oral vaccines in transgenic plants. National and international impact: 5, focusing, relevance: 4, quality and quantity: 5. In the section also the question of waning immunity after MMR vaccine has been studied recently. It has relevance for the future planning of the national childhood vaccination policy. A further line of research deals with the implementation of rotavirus vacci- nations in children. Studies include epidemiological and immuno- logical studies. Both research fields have high level of relevance while the scientific value is moderate-to-good. In the section of viral zoonoses ( headed by prof. Å.Lundkvist) several important projects are running: The section is part of the EU-wide EDEN-project that is respon- ding to the emerging threats due to environmental change in Europe. It is working as a reference laboratory for the project and has special emphasis on hantaviruses where it also serves as a EU reference center. The section is also employed in developing reliable diagnostic tests for the surveillance of rare (in ) infections such as West infections, chikungunya and dengue, all increasingly important as candidates for import cases from en- demic areas due to increasing tourism. The researchers, using the availability of high-containment facilities are also working on the development of diagnostic tools and eventually vaccine against Rift valley fever, now con- sidered as most important zoonotic infection. In and around the Baltic Sea, the issue of possible expanding of TBE endemic areas is also touched as well as pos- sible vaccine failures. All these studies show excellent scientific value and their relevance to public health in general and to the work of SMI is excellent. National and international impact: 5, focusing, relevance: 5, quality and quantity: 5. The section is also employed in surveying birds for viruses that are pathogenic for human beings including such well-known pathogens as avian influenza virus, West virus and virus. The work is done in collaboration with a bird observatory in . Being part of the national preparedness for emerging threats, the work is highly relevant to the mission of SMI. The work is also extended to other types of viruses such as cowpox and LCMV. It may be asked to what extent the work sup- ports early finding of clinical cases in (by supporting labo- ratory diagnostics etc). Scientific merits good to moderate while the relevance to SMI excellent. National and international impact: 4, focusing, relevance: 5, quality and quantity: 4. The section with its BSL-4 capacity is an important component of network for dangerous emerging viruses. By maintaining sufficient research activity dealing with agents that cannot be handled safely outside high level BSLs the laboratory ensures also that proper diagnostic applications and control measu- res can be developed rapidly if agents with new properties emerge, as exemplified by SARS coronavirus a few years ago. As such it is of great importance and highly relevant for SMI. The scientific quality of the work has been good with excellent relevance both in general and for SMI . National and international impact: 4, focusing, relevance: 5, quality and quantity: 3. In the section of virology (A. ) Epstein-Barr virus infec- tions have been studied in detail. The works dealing with EBV reactivation in malaria shed new light in the pathogenesis of these infections. This work has moderate scientific importance and the public health and SMI relevance is moderate-to-low. The section of HIV and retroviruses (J.Albert) demonstrate a wide array and impressive quantity of high-level scientific research projects. One project is responsible for surveillance and research on transmission of drug resistant in . Currently the laboratory receives samples from about of all new HIV cases all over . This is part of a pan-European network that follows emergence of drug resistance among new HIV-cases. This is a national and international reference laboratory function and has resulted in recommendations concerning this important issue. Linked with this, the laboratory is also following the molecular epidemiology and phylodynamics of HIV infections in . This provides tools for more precise situation analysis and identifi- cation of local outbreaks with common sources, even transmission chains. The laboratory is also employing new highly effective sequencing technologies that will allow even more detailed mole- cular epidemiology surveillance of HIV (and several other viruses). Scientific merit of these HIV-related research projects varies from moderate to good, and relevance to SMI excellent. National and international impact: 4, focusing, relevance: 5, quality and quantity: 4. (Comment: The increasing capacity of laboratories to produce sequence and other detailed data from microbes increases the need for biostatistical expertice. This need is not restricted to the department of virology but is evident in almost all other depart- ments also. Centralising and expanding biostatistical and epidemi- ological resources would be useful for the entire scientific output of SMI.) The department has also projects supporting the development of vaccines against HIV-1. Some of it is very basic immunological work i.e. identification of broadly epitopes using synthetic peptides which could be useful for the vaccine develop- ment. In the other end, a novel vaccine that has shown very pro- mising results in initial trials is now entering to a multi-site phase II trial in and . Several other candidate vac- cines are also being developed and tested in humans. These projects are led by prof. . Their scientific merits are good-to- excellent and they show good relevance to the work of SMI in ge- neral. National and international impact: 4, focusing, relevance: 5, quality and quantity: 4. The HIV portfolio has grown very much in SMI and KI during the last two decades and the campus forms an internationally im- portant and recognized hub for HIV vaccine studies. A significant majority of funding comes from external, usually international resources reflecting also the high quality and relevance of the work. Part of this work is rather basic academic research, and its direct relevance to the work of SMI could be questioned.