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October 2016 - First VacTrainee successfully defended thesis

On the 4th of October, Benedict Halbroth (Germany) successfully defended his thesis entitled 'Development of Adjuvanted Multi Antigen Liver Stage Malaria Vaccines'. Halbroth performed his PhD studies under the supervision of Prof. Adrian Hill at the Jenner Institute, University of Oxford, UK. 

 


 

September 2016 - Vaccine confidence, essential for an effective uptake of vaccines

Vaccine trust and the limits of information. Over the past decade, there has been growing recognition and increasing research around the phenomenon of vaccine reluctance and refusal. More recently, there has been a flurry of articles on what is being referred to as “vaccine hesitancy,” depolarizing the earlier characterization of individuals or groups as being outright pro- or antivaccine, and instead recognizing the liminal state between becoming aware of, and deciding whether or not to accept, vaccination. Episodes of waning public confidence around vaccines have become so global that the World Health Organization's Strategic Advisory Group of Experts on Immunization convened a working group to better understand and recommend actions to address this growing challenge of vaccine hesitancy, which the group defined as “delay in acceptance or refusal of vaccination despite availability of vaccination services.” Indeed, vaccine hesitancy is complex and context specific. How can we better understand the circumstances that influence this state to ensure more effective uptake of vaccines and secure public health? Science. 2016 Sep 16;353(6305):1207-8.

 

See also: The State of Vaccine Confidence 2016: Global Insights Through a 67-Country Survey. EBioMedicine. 2016 Oct;12:295-301.

See also: The Vaccine Confidence Project.

 


 

September 2016 - Publication by Eleni Panagioti

The Breadth of Synthetic Long Peptide Vaccine-Induced CD8+ T Cell Responses Determines the Efficacy against Mouse Cytomegalovirus Infection. There is an ultimate need for efficacious vaccines against human cytomegalovirus (HCMV), which causes severe morbidity and mortality among neonates and immunocompromised individuals. In this study we explored synthetic long peptide (SLP) vaccination as a platform modality to protect against mouse CMV (MCMV) infection in preclinical mouse models. In both C57BL/6 and BALB/c mouse strains, prime-booster vaccination with SLPs containing MHC class I restricted epitopes of MCMV resulted in the induction of strong and polyfunctional (i.e., IFN-γ+, TNF+, IL-2+) CD8+ T cell responses, equivalent in magnitude to those induced by the virus itself. SLP vaccination initially led to the formation of effector CD8+ T cells (KLRG1hi, CD44hi, CD127lo, CD62Llo), which eventually converted to a mixed central and effector-memory T cell phenotype. Markedly, the magnitude of the SLP vaccine-induced CD8+ T cell response was unrelated to the T cell functional avidity but correlated to the naive CD8+ T cell precursor frequency of each epitope. Vaccination with single SLPs displayed various levels of long-term protection against acute MCMV infection, but superior protection occurred after vaccination with a combination of SLPs. This finding underlines the importance of the breadth of the vaccine-induced CD8+ T cell response. Thus, SLP-based vaccines could be a potential strategy to prevent CMV-associated disease. PLoS Pathog. 2016 Sep 16;12(9):e1005895

 


 

June 2016 - Publication by Claudia Lindemann

Risk factors for dermatitis in submariners during a submerged patrol: an observational cohort study. OBJECTIVE: The aim of this pilot study was to determine risk factors, including Staphylococcus aureus nasal carriage, for dermatitis in submariners during a submarine patrol. PARTICIPANTS AND METHODS: 36 submariners undertaking a submerged 6-week patrol participated in the study. Severity of dermatitis and its impact was assessed using visual analogue scales and questionnaires at baseline and weekly throughout the patrol. S. aureus carriage levels in submariners were determined by nasal swabbing at baseline and shortly before disembarking the submarine. Occurrence of any skin or soft tissue infections (SSTI) were reported to the medical officer and swabs of the area were taken for subsequent analysis. RESULTS: S. aureus carriers were significantly more likely than non-carriers to have previously received treatment for a cutaneous abscess (39% vs 5%, OR=13 (95% CI 1.3 to 130)) with a trend to being submariners longer (p=0.051). Skin scores at baseline and on patrol were not significantly associated with carriage status. Higher dermatitis scores were observed in those who had been submariners longer (p=0.045). Smoking and allergies were not found to be linked to carriage status or skin health score in this cohort. CONCLUSIONS: This small pilot study investigates S. aureus carriage status and skin health in submariners. Length of submarine service but not S. aureus carriage was identified as a risk factor for worsening skin health in this small cohort during a 6-week patrol. This does not support S. aureus decolonisation to improve skin health in this population. Further investigation into causes of dermatitis in submariners is required. This data supports a better understanding of the potential impact of exposure to environmental factors that could affect skin health in submariners. BMJ Open. 2016 Jun;6(6):e010975.

 


 

June 2016 – Publication by Esther Oiknine-Djian

CEACAM1-Mediated Inhibition of Virus Production. Cells in our body can induce hundreds of antiviral genes following virus sensing, many of which remain largely uncharacterized. CEACAM1 has been previously shown to be induced by various innate systems; however, the reason for such tight integration to innate sensing systems was not apparent. Here, we show that CEACAM1 is induced following detection of HCMV and influenza viruses by their respective DNA and RNA innate sensors, IFI16 and RIG-I. This induction is mediated by IRF3, which bound to an ISRE element present in the human, but not mouse, CEACAM1 promoter. Furthermore, we demonstrate that, upon induction, CEACAM1 suppresses both HCMV and influenza viruses in an SHP2-dependent process and achieves this broad antiviral efficacy by suppressing mTOR-mediated protein biosynthesis. Finally, we show that CEACAM1 also inhibits viral spread in ex vivo human decidua organ culture. Cell Rep. 2016 Jun;15(11):2331-9.

 


 

May 2016 - Publication by Claudia Lindemann

Natural mutations in a Staphylococcus aureus virulence regulator attenuate cytotoxicity but permit bacteremia and abscess formation. Staphylococcus aureus is a major bacterial pathogen, which causes severe blood and tissue infections that frequently emerge by autoinfection with asymptomatically carried nose and skin populations. However, recent studies report that bloodstream isolates differ systematically from those found in the nose and skin, exhibiting reduced toxicity toward leukocytes. In two patients, an attenuated toxicity bloodstream infection evolved from an asymptomatically carried high-toxicity nasal strain by loss-of-function mutations in the gene encoding the transcription factor repressor of surface proteins (rsp). Here, we report that rsp knockout mutants lead to global transcriptional and proteomic reprofiling, and they exhibit the greatest signal in a genome-wide screen for genes influencing S. aureus survival in human cells. This effect is likely to be mediated in part via SSR42, a long-noncoding RNA. We show that rsp controls SSR42 expression, is induced by hydrogen peroxide, and is required for normal cytotoxicity and hemolytic activity. Rsp inactivation in laboratory- and bacteremia-derived mutants attenuates toxin production, but up-regulates other immune subversion proteins and reduces lethality during experimental infection. Crucially, inactivation of rsp preserves bacterial dissemination, because it affects neither formation of deep abscesses in mice nor survival in human blood. Thus, we have identified a spontaneously evolving, attenuated-cytotoxicity, nonhemolytic S. aureus phenotype, controlled by a pleiotropic transcriptional regulator/noncoding RNA virulence regulatory system, capable of causing S. aureus bloodstream infections. Such a phenotype could promote deep infection with limited early clinical manifestations, raising concerns that bacterial evolution within the human body may contribute to severe infection. Proc Natl Acad Sci U S A. 2016 May 31;113(22):E3101-10.

 


 

May 2016 - Publication by Claudia Lindemann

MRI Based Localisation and Quantification of Abscesses following Experimental S. aureus Intravenous Challenge: Application to Vaccine Evaluation. PURPOSE: To develop and validate a sensitive and specific method of abscess enumeration and quantification in a preclinical model of Staphylococcus aureus infection. METHODS: S. aureus infected murine kidneys were fixed in paraformaldehyde, impregnated with gadolinium, and embedded in agar blocks, which were subjected to 3D magnetic resonance microscopy on a 9.4T MRI scanner. Image analysis techniques were developed, which could identify and quantify abscesses. The result of this imaging was compared with histological examination. The impact of a S. aureus Sortase A vaccination regime was assessed using the technique. RESULTS: Up to 32 murine kidneys could be imaged in a single MRI run, yielding images with voxels of about 25 μm3. S. aureus abscesses could be readily identified in blinded analyses of the kidneys after 3 days of infection, with low inter-observer variability. Comparison with histological sections shows a striking correlation between the two techniques: all presumptive abscesses identified by MRI were confirmed histologically, and histology identified no abscesses not evident on MRI. In view of this, simulations were performed assuming that both MRI reconstruction, and histology examining all sections of the tissue, were fully sensitive and specific at abscess detection. This simulation showed that MRI provided more sensitive and precise estimates of abscess numbers and volume than histology, unless at least 5 histological sections are taken through the long axis of the kidney. We used the MRI technique described to investigate the impact of a S. aureus Sortase A vaccine. CONCLUSION: Post mortem MRI scanning of large batches of fixed organs has application in the preclinical assessment of S. aureus vaccines. PLoS One. 2016 May 26;11(5):e0154705.

 


 

December 2015 - Ending the HIV–AIDS Pandemic

In July 1996, researchers, policymakers, and activists involved in the fight against HIV–AIDS met in Vancouver, Canada, for the 11th International Conference on AIDS. During that historic meeting, practitioners and patients heard evidence regarding a powerful weapon to stop the relentless onslaught of the human immunodeficiency virus (HIV): combination antiretroviral therapy (ART), with a protease inhibitor as the centerpiece of the regimen. In the nearly 20 years since that watershed meeting, the early promise of durable effects from combination therapy has been realized for many patients: between 2000 and 2014, the rollout of ART saved an estimated 7.8 million lives worldwide. Studies described in this publication provide an evidence-based blueprint for effective treatment and prevention of HIV infection and will serve as critical tools in the fight to end the HIV–AIDS pandemic. However, in order to realize that promise, the political will must be mobilized to match the scientific evidence and provide the financial and human resources necessary to dramatically scale up HIV testing and treatment around the world. The science has spoken. There can now be no excuse for inaction. N Engl J Med. 2015 Dec 3;373(23):2197-9.

 

Other interesting papers to this subject are: 

Toward an HIV vaccine: A scientific journey. Science. 2015 Jul 24;349(6246):386-7.

The modern era of HIV-1 vaccine development. Science. 2015 Jul 10;349(6244):139-40.

 


 

December 2015 - Publication by Benedict Halbroth

Identification of Immunodominant Responses to the Plasmodium falciparum Antigens PfUIS3, PfLSA1 and PfLSAP2 in Multiple Strains of Mice. Malaria, caused by the Plasmodium parasite, remains a serious global public health concern. A vaccine could have a substantial impact on eliminating this disease, alongside other preventative measures. We recently described the development of three novel, viral vectored vaccines expressing either of the antigens PfUIS3, PfLSA1 and PfLSAP2. Each vaccination regimen provided high levels of protection against chimeric parasite challenge in a mouse model, largely dependent on CD8+ T cells. In this study we aimed to further characterize the induced cellular immune response to these vaccines. We utilized both the IFNγ enzyme-linked immunosorbent spot assay and intracellular cytokine staining to achieve this aim. We identified immunodominant peptide responses for CD4+ and CD8+ T cells for each of the antigens in BALB/c, C57BL/6 and HLA-A2 transgenic mice, creating a useful tool for researchers for subsequent study of these antigens. We also compared these immunodominant peptides with those generated from epitope prediction software, and found that only a small proportion of the large number of epitopes predicted by the software were identifiable experimentally. Furthermore, we characterized the polyfunctionality of the induced CD8+ T cell responses. These findings contribute to our understanding of the immunological mechanisms underlying these protective vaccines, and provide a useful basis for the assessment of these and related vaccines as clinical constructs. PLoS One. 2015 Dec 11;10(12):e0144515.

 


 

November 2015 – Publication by Esther Oiknine-Djian

Human cytomegalovirus induces a distinct innate immune response in the maternal-fetal interface. The initial interplay between human cytomegalovirus (HCMV) and innate tissue response in the human maternal-fetal interface, though crucial for determining the outcome of congenital HCMV infection, has remained unknown. We studied the innate response to HCMV within the milieu of the human decidua, the maternal aspect of the maternal-fetal interface, maintained ex vivo as an integral tissue. HCMV infection triggered a rapid and robust decidual-tissue innate immune response predominated by interferon (IFN)γ and IP-10 induction, dysregulating the decidual cytokine/chemokine environment in a distinctive fashion. The decidual-tissue response was already elicited during viral-tissue contact, and was not affected by neutralizing HCMV antibodies. Of note, IFNγ induction, reflecting immune-cell activation, was distinctive to the maternal decidua, and was not observed in concomitantly-infected placental (fetal) villi. Our studies in a clinically-relevant surrogate human model, provide a novel insight into the first-line decidual tissue response which could affect the outcome of congenital infection. Virology. 2015 Nov;485:289-96.

 


 

November 2015 – Publication by Esther Oiknine-Djian

Transition toward Human Cytomegalovirus Susceptibility in Early Human Embryonic Stem Cell-Derived Neural Precursors. Congenital human cytomegalovirus (HCMV) infection is associated with neurodevelopmental disabilities. To dissect the earliest events of infection in the developing human brain, we studied HCMV infection during controlled differentiation of human embryonic stem cells (hESC) into neural precursors. We traced a transition from viral restriction in hESC, mediated by a block in viral binding, toward HCMV susceptibility in early hESC-derived neural precursors. We further revealed the role of platelet-derived growth factor receptor alpha (PDGFRα) as a determinant of the developmentally acquired HCMV susceptibility. J Virol. 2015 Nov;89(21):11159-64.

 


 

October 2015 - Malaria vaccine cautiously recommended for use in Africa

The world's first vaccine against malaria should be rolled out in limited 'pilot' demonstrations in Africa, an advisory group to the World Health Organization (WHO) in Geneva said on 23 October. The demonstrations — involving up to 1 million children — are needed because the vaccine is ineffective against malaria unless children receive four doses spread out over 18 months, and even then offers only modest protection. The decision to recommend the vaccine pilots — which the WHO’s director-general is expected to formally endorse in November — follows 28 years of development by the London-based drug firm GlaxoSmithKline (GSK) and other backers including the Bill & Melinda Gates Foundation in Seattle, Washington; together they have spent US$565 million on the drug. Nature. 2015 Oct 29;526(7575):617-8.

 

Other interesting papers to this subject are:

Genetic diversity and protective efficacy of the RTS,S/AS01 malaria vaccine. N Engl J Med 2015; 373:2025-2037.

 



August 2015 - VacTrain on HorizonHealthLogo HorizonHealth

Within its FP7 HEALTH programme, the European Commission has funded a special project called CommHERE, Communicating European Health Research. The aim of CommHERE is to improve communication on the outcome of EU funded health research projects to the general public and the media. An important channel to do this is the HorizonHealth.eu webportal. 

 


 

August 2015 - Countering antivaccination attitudes

Myths about the safety of vaccinations have led to a decline in vaccination rates and the reemergence of measles in the United States, calling for effective provaccine messages to curb this dangerous trend. Prior research on vaccine attitude change suggests that it is difficult to persuade vaccination skeptics and that direct attempts to do so can even backfire. Here, we successfully countered people’s antivaccination attitudes by making them appreciate the consequences of failing to vaccinate their children (using information provided by the Centers for Disease Control and Prevention). This intervention outperformed another that aimed to undermine widespread vaccination myths. Three times as many cases of measles were reported in the United States in 2014 as in 2013. The reemergence of measles has been linked to a dangerous trend: parents refusing vaccinations for their children. Efforts have been made to counter people’s antivaccination attitudes by providing scientific evidence refuting vaccination myths, but these interventions have proven ineffective. This study shows that highlighting factual information about the dangers of communicable diseases can positively impact people’s attitudes to vaccination. This method outperformed alternative interventions aimed at undercutting vaccination myths. Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10321-4.

 


 

August 2015 - Dangers of vaccine refusal near the herd immunity threshold: a modelling study

Childhood vaccination remains the focus of heated public debate. Parents struggle to understand the potential risks associated with vaccination but both parents and physicians assume that they understand the risks associated with infection. This study was done to characterise how modern vaccination practices have altered patient risks from infection.

As vaccination makes preventable illness rarer, for some diseases, it also increases the expected severity of each case. Because estimates of case risks rely on data for severity generated during a pre-vaccine era they underestimate negative outcomes in the modern post-vaccine epidemiological landscape. Physicians and parents should understand when making decisions about their children's health and safety that remaining unvaccinated in a predominantly vaccine-protected community exposes their children to the most severe possible outcomes for many preventable diseases. The Lancet Infectious Diseases 2015; 15:922-6.

 


 

July 2015 - World's first malaria vaccine

The green light has been given by European regulators for the world's first malaria vaccine. The European Medicines Agency is recommending the drug be licensed for use in babies in Africa. See movie.

 


 

July 2015 - Nigeria almost free of polio

Just three years ago, Nigeria was a threat to the global push to eradicate polio. Africa’s most populous nation recorded 122 cases in 2012, more than all other countries combined, and funders of the eradication campaign were growing exasperated with the nation’s faltering vaccination efforts and exportation of cases. Now Nigeria is on the brink of being free of the virus, thanks in large part to its embrace of innovative approaches to vaccination and public health. Nature. 2015 Jul 16;523(7560):263-4.

 


 

July 2015 - Publication by Mariateresa Coppola

Synthetic long peptide derived from M. tuberculosis latency antigen Rv1733c protects against tuberculosis. Responsible for 9 million new cases of active disease and nearly 2 million deaths each year, tuberculosis (TB) remains a global health threat of overwhelming dimensions. BCG, the only licensed vaccine available, fails to confer lifelong protection and to prevent reactivation of latent infection. Although 15 new vaccine candidates are now in clinical trials, an effective vaccine against TB remains elusive and new strategies for vaccination are vital. BCG vaccination fails to induce immunity against Mycobacterium tuberculosis (Mtb) latency antigens.Synthetic long peptides (SLP) combined with adjuvants have been studied mostly for therapeutic cancer vaccines, yet not for TB, and proved to induce efficient antitumor immunity. This study, investigated an SLP derived from Rv1733c, a major Mtb latency antigen which is highly expressed by "dormant" Mtb and well recognized by T-cells from latently Mtb-infected individuals.In order to assess its in vivo immunogenicity and protective capacity, Rv1733c SLP in CpG was administrated to HLA-DR3 transgenic mice. Immunization with Rv1733c SLP elicited IFN-γ+/TNF+ and IFN-γ+ CD4+ T-cells CD4+ T-cells, Rv1733c specific antibodies and led to a significant reduction in the bacterial load in the lungs of Mtb challenged mice. This was observed both in a pre- and in a post Mtb challenge setting. Moreover, Rv1733c SLP immunisation significantly boosted the protective efficacy of BCG demonstrating the potential of Mtb latency antigens to improve BCG efficacy. These data suggest a promising role for Mtb latency antigen Rv1733c-derived SLPs as a novel TB vaccine approach, both in a prophylactic as well as post-infection setting. Clin Vaccine Immunol. 2015 Jul 22. pii: CVI.00271-15.

 


 

July 2015 - Establishing a Global Vaccine-Development Fund

Vaccine development is facing a crisis for three reasons: the complexity of the most challenging targets, which necessitates substantial investment of capital and human expertise; the diminishing numbers of vaccine manufacturers able to devote the necessary resources to research, development, and production; and the prevailing business model, which prioritizes the development of vaccines with a large market potential. We consider an international vaccine-development fund to be urgently needed to provide the resources and the momentum to carry vaccines from their conception in academic and government laboratories and small biotechnology firms to development and licensure by industry. Such a fund would enable basic scientists to move candidate vaccines from the laboratory through the so-called valley of death — the critical steps after good preclinical data have been obtained, comprising manufacture to Food and Drug Administration standards, a phase 1 clinical trial, and proof of concept in terms of protective immune responses. This support would permit efficacy assessment to begin — and thereby avert a repetition of the Ebola crisis. N Engl J Med. 2015 Jul 23;373(4):297-300.

 


 

July 2015 - Shifting Vaccination Politics - The end of personal-belief exemptions in California

It's not often that California, West Virginia, and Mississippi are politically aligned, but that unlikely trio formed on June 25, 2015, when California Governor Jerry Brown signed into law Senate Bill (SB) 277, substantially narrowing exceptions to school-entry vaccination mandates. With that law, California becomes the third state to disallow exemptions based on both religious and philosophical beliefs; only medical exemptions remain. The move represents a stunning victory for public health that affects not only California school children but also the prospects for strengthening vaccination requirements nationwide. N Engl J Med. 2015 Jul 22.

 


 

July 2015 - Oral cholera vaccine trial

Cholera is endemic in Bangladesh with epidemics occurring each year. The decision to use a cheap oral killed whole-cell cholera vaccine to control the disease depends on the feasibility and effectiveness of vaccination when delivered in a public health setting. We therefore assessed the feasibility and protective effect of delivering such a vaccine through routine government services in urban Bangladesh and evaluated the benefit of adding behavioural interventions to encourage safe drinking water and hand washing to vaccination in this setting. Our findings provide the first indication of the effect of delivering an oral killed whole-cell cholera vaccine to poor urban populations with endemic cholera using routine government services and will help policy makers to formulate vaccination strategies to reduce the burden of severely dehydrating cholera in such populations. Lancet. 2015 Jul 8. pii:S0140-6736(15)61140-0. 

 

Comment 'Oral cholera vaccines in endemic countries'. Lancet. 2015 Jul 8. pii: S0140-6736(15)60246-X. 

 



 

July 2015 - Narcolepsy link to pandemic flu vaccine becomes clearer

The 2009 H1N1 influenza pandemic left a troubling legacy in Europe: More than 1300 people who received a vaccine to prevent the flu developed narcolepsy, an incurable, debilitating condition that causes overpowering daytime sleepiness, sometimes accompanied by a sudden muscle weakness in response to strong emotions such as laughter or anger. The manufacturer, GlaxoSmith-Kline (GSK), has acknowledged the link, and some patients and their families have already been awarded compensation. But how the vaccine might have triggered the condition has been unclear. In a paper in Science Translational Medicine (STM) this week, researchers offer a possible explanation. They show that the vaccine, called Pandemrix, triggers antibodies that can also bind to a receptor in brain cells that help regulate sleepiness. The work strongly suggests that Pandemrix, which was given to more than 30 million Europeans, triggered an autoimmune re action that led to narcolepsy in some people who are genetically at risk. Science 2015; 349:17.

 


 

May 2015 - Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality

Immunosuppression after measles is known to predispose people to opportunistic infections for a period of several weeks to months. Using population-level data, we show that measles has a more prolonged effect on host resistance, extending over 2 to 3 years. We find that nonmeasles infectious disease mortality in high-income countries is tightly coupled to measles incidence at this lag, in both the pre- and post-vaccine eras. We conclude that long-term immunologic sequelae of measles drive interannual fluctuations in nonmeasles deaths. This is consistent with recent experimental work that attributes the immunosuppressive effects of measles to depletion of B and T lymphocytes. Our data provide an explanation for the long-term benefits of measles vaccination in preventing all-cause infectious disease. By preventing measles-associated immune memory loss, vaccination protects polymicrobial herd immunity. Science 2015; 348:694-9.

 


 

20-25 April 2015 - European Immunization Week

The theme of the European Immunzation Week 2015 is: Commitment to immunization – how can Europe free itself from vaccine-preventable diseases? Immunization has saved more lives than any other public health intervention, yet 2013 saw 31 685 measles cases alone in Europe, an increase of 348% compared to 2007. The cost of these outbreaks in both human and monetary terms is extremely high. To move closer to WHO’s vision of a European Region free of vaccine-preventable diseases, renewed commitment and innovative approaches are needed, as set out in the European Vaccine Action Plan 2015–2020 (EVAP). The 10th European Immunization Week, on 20–25 April 2015, focuses on the need for renewed commitment to immunization at political, professional and personal levels. Communication and advocacy activities will celebrate progress achieved so far – particularly towards elimination of measles and rubella, maintaining the Region’s polio-free status, and introduction of new vaccines  – and focus on what immediate action needs to be taken to maintain momentum and achieve the Region’s ambitious immunization goals. Examples of new policies and initiatives will illustrate innovative ways to address the key factors affecting immunization decisions: complacency, confidence, convenience and access. As in previous years, European Immunization Week 2015 will coincide with the global World Immunization Week campaign spearheaded by WHO headquarters. This year’s campaign focuses on closing the immunization gap and reaching equity in immunization levels as outlined in the Global Vaccine Action Plan (GVAP) - the global framework upon which EVAP is based.

 


 

April 2015 - Publication by Benedict Halbroth

Recent developments in malaria vaccinology. The development of a highly effective malaria vaccine remains a key goal to aid in the control and eventual eradication of this devastating parasitic disease. The field has made huge strides in recent years, with the first-generation vaccine RTS,S showing modest efficacy in a Phase III clinical trial. The updated 2030 Malaria Vaccine Technology Roadmap calls for a second generation vaccine to achieve 75% efficacy over two years for both Plasmodium falciparum and Plasmodium vivax, and for a vaccine that can prevent malaria transmission. Whole-parasite immunisation approaches and combinations of pre-erythrocytic subunit vaccines are now reporting high-level efficacy, whilst exciting new approaches to the development of blood-stage and transmission-blocking vaccine subunit components are entering clinical development. The development of a highly effective multi-component multi-stage subunit vaccine now appears to be a realistic ambition. This review will cover these recent developments in malaria vaccinology. Adv Parasitol. 2015; 88:1-49.

 


 

March 2015 - Bill Gates warns the world for next virus outbreak

TED (Ideas worth spreading) talk by Bill Gates. Gates warns the world "We are not ready for the next virus outbreak". In 2014, the world avoided a global outbreak of Ebola, thanks to thousands of selfless health workers — plus, frankly, some very good luck. In hindsight, we know what we should have done better. So, now's the time, Bill Gates suggests, to put all our good ideas into practice, from scenario planning to vaccine research to health worker training. As he says, "There's no need to panic ... but we need to get going." In addition, Gates publishes anarticle about this in the New England Journal of Medicine.

 


 

February 2015 – Publication by Esther Oiknine-Djian
Dynamic Co-evolution of Host and Pathogen: HCMV Downregulates the Prevalent Allele MICA∗008 to Escape Elimination by NK Cells. Natural killer (NK) cells mediate innate immune responses against hazardous cells and are particularly important for the control of human cytomegalovirus (HCMV). NKG2D is a key NK activating receptor that recognizes a family of stress-induced ligands, including MICA, MICB, and ULBP1-6. Notably, most of these ligands are targeted by HCMV proteins and a miRNA to prevent the killing of infected cells by NK cells. A particular highly prevalent MICA allele, MICA∗008, is considered to be an HCMV-resistant "escape variant" that confers advantage to human NK cells in recognizing infected cells. However, here we show that HCMV uses its viral glycoprotein US9 to specifically target MICA∗008 and thus escapes NKG2D attack. The finding that HCMV evolved a protein dedicated to countering a single host allele illustrates the dynamic co-evolution of host and pathogen. Cell Rep. 2015 Feb 12. pii: S2211-1247(15)00054-6.

 


 

January 2015 - Publication by Ilona Baraniak
The pathogenesis of human cytomegalovirus. Human cytomegalovirus (HCMV) is a recognized cause of disease in the fetus, the allograft recipient and AIDS patients. More recently, it has been recognized as a pathogen for those admitted to intensive care units, for the elderly and for the general population. The epidemiology and molecular and cellular pathology of this virus are summarized to provide an overarching model of pathogenesis, able to account for these varying clinical presentations. In brief, HCMV has the potential to spread in the bloodstream to all organs, but only produces overt disease if the viral load increases to high levels. This is normally prevented by a robust immune response, so that the infected individual usually remains asymptomatic. However, this benefit comes at the cost of committing more and more immunological resources to controlling HCMV with time, so that the overall function of the immune system is impaired. Fortunately, recent progress in developing novel antiviral drugs and vaccines suggests the possibility that the diverse effects of HCMV may soon become controllable at the individual and population level, respectively. J Pathol. 2015 Jan;235(2):288-97.

 


 

January 2015 - Publication by Ioanna Christopoulou
Influenza vaccines to control influenza-associated bacterial infection: where do we stand? Influenza A virus is a pathogen that is feared for its capacity to cause pandemics. In this review, we illustrate the clinical evidence which support the theory that bacterial co-infection is a considerable risk factor for exacerbated disease during pandemic and seasonal influenza, including infection with influenza B viruses. We provide an overview of the multiple and diverse mechanisms that help explain how influenza creates an opportunity for replication of secondary bacterial infections. Influenza vaccines and pneumococcal vaccines are widely used and often in overlapping target groups. We summarize the evidence for a protective effect of influenza immunization against bacterial infections, and vice versa of pneumococcal vaccines against influenza-associated pneumonia and lethality. It is important that future implementation of broadly protective influenza vaccines also takes into account protection against secondary bacterial infection. Expert Rev Vaccines. 2015 Jan;14(1):55-67.

 


 

January 2015 – Annemieke Geluk appointed full professor at LUMC
Dr. Annemieke Geluk of the department of Infectious Diseases of the LUMC in Leiden, the Netherlands, has been appointed full professor of Immune Diagnostics of Mycobacterial Infectious Diseases. Following her masters in Chemistry at the University of Leiden and the University of Virginia, Charlottesville, USA, she did her PhD in Immunology at the LUMC (HLA-DR3/ Peptide/ T cell Interactions) and worked at Cytel Corporation, San Diego, USA. She received postdoctoral training at the Mayo Clinic, Rochester, MN, USA and was acknowledged a 5-year fellowship by the Royal Dutch Academy of Sciences during which period she focused on the immunology of leprosy and tuberculosis, particularly the identification of HLA-restricted T cell (epitopes) that are essential to protective immunity or immunopathology, and biomarkers for development of immunodiagnostics. Her current research focuses on Immunodiagnostics of Leprosy including basic-, translational-, applied- as well as field research and Tuberculosis Vaccine Development using HLA transgenic mouse models. Currently, she is a member of the steering committee of the IDEAL consortium (Initiative for Diagnostic and Epidemiological Assays for Leprosy) and has designed and coordinated several large-scale, multi-centre studies in e.g. Bangladesh, Brazil, Ethiopia and Nepal.

 


 

November 2014 - Launch VacTrain movie

During the 2nd consortium meeting of VacTrain in Leiden, the Netherlands, all ESRs were interviewed about their research, training and personal experiences in VacTrain. See movie.   

 


 

June 2014 - Publication by Mariateresa Coppola
Clonal analysis of the T-cell response to in vivo expressed Mycobacterium tuberculosis protein Rv2034, using a CD154 expression based T-cell cloning method. Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a leading cause of death worldwide. A better understanding of the role of CD4+ and CD8+ T cells, which are both important to TB protection, is essential to unravel the mechanisms of protection and to identify the key antigens seen by these T cells. We have recently identified a set of in vivo expressed Mtb genes (IVE-TB) which is expressed during in vivo pulmonary infection in mice, and shown that their encoded antigens are potently recognized by polyclonal T cells from tuberculin skin test-positive, in vitro ESAT-6/CFP10-responsive individuals. Here we have cloned T cells specific for one of these newly identified in vivo expressed Mtb (IVE-TB) antigens, Rv2034. T cells were enriched based on the expression of CD154 (CD40L), which represents a new method for selecting antigen-specific (low frequency) T cells independent of their specific function. An Rv2034-specific CD4+ T-cell clone expressed the Th1 markers T-bet, IFN-γ, TNF-α, IL-2 and the cytotoxicity related markers granzyme B and CD107a as measured by flow cytometry. The clone specifically recognized Rv2034 protein, Rv2034 peptide p81-100 and Mtb lysate. Remarkably, while the recognition of the dominant p81-100 epitope was HLA-DR restricted, the T-cell clone also recognized a neighboring epitope (p88-107) in an HLA-DR- as well as HLA-DQ1-restricted fashion. Importantly, the T-cell clone was able to inhibit Mtb outgrowth from infected monocytes significantly. The characterization of the polyfunctional and Mtb inhibitory T-cell response to IVE-TB Rv2034 at the clonal level provides detailed further insights into the potential of IVE-TB antigens as new vaccine candidate antigens in TB. Our new approach allowed the identification of T-cell subsets that likely play a significant role in controlling Mtb infection, and can be applied to the analysis of T-cell responses in patient populations. PLoS One. 2014 Jun 6;9(6):e99203.
 


 

03 June 2014 - Launch VacTrain blog

Our first blog has been posted on our blog-site: News from the vaccine world. This blog gives an introduction to the Vaccine World and VacTrain in particular. In later blogs you will hear more from our VacTrainees. What inspires them to follow this research and training programme, what have they learned and experienced so far, and what are their dreams and future goals. We will also regularly update you on new developments from within the vaccine world. 

 


 

24-30 April 2014 - World Immunization Week

The theme of this years World Immunization Week is: 'Are you up-to-date?'. World Immunization Week is an opportunity to remind families and communities how effective vaccines can be, and to encourage people to take action to ensure that more children, and increasingly people in other age groups, are immunized against deadly and debilitating diseases. Today, immunization averts 2-3 million deaths each year from diseases such as diphtheria, measles, pertussis, pneumonia, polio, rotavirus diarrhoea, rubella and tetanus. One important driver of this progress has been the Expanded Programme on Immunization (EPI), which celebrates its 40th anniversary in May 2014.

 


 

05 March 2014 - VacTrain ESRs receive their first travel grants

Both Ilona Baraniak (University College Londen) and Claudia Lindemann (University of Oxford) have been awarded a travel grant. These grants enable them to attend the Annual Conference of the Society for General Microbiology in Liverpool-UK and EVImalar Career Development and Gender Conference in Rome-Italy, respectively. In addition, Benedict Halbroth (University of Oxford) has been selected by the scientific review panel of the Council for the Lindau Nobel Laureate Meetings to participate in the 64th Lindau Nobel Laureate Meeting in Lindau-Germany. 

 


 

22-23 November 2013 - Kick-off meeting VacTrain

On November 22-23, all partners, associate partners, VacTrainees and advisory committee members gathered at the Rewley House in Oxford, UK. The Kick-off meeting was the first opportunity, since the start of the project on November 1 2012, for all persons invloved in VacTrain to meet each other. Management meetings were held, collaborations set-up and strengthened, and all VacTrainees presented their research projects. A guest lecture entitled 'New Challenges for Vaccines and for Vaccinologists' was provided by Paul-Henri Lambert.   

 


 

18-22 November 2013 - Human and Veterinary Vaccinology course for VacTrainees

In November, our VacTrainees followed the 5-day course Human and Veterinary Vaccinology organised by the University of Oxford in Oxford, UK. This Master's level course covered all aspects of vaccinology and provided an overview of the field of human and veterinary vaccinology, from Edward Jenner to modern day vaccines. During the course, which was according to the VacTrainees very intensive, but of high interest and high quality, the VacTrainees had the opportunity to meet and get to know each other.

 


 

17 October 2013 - Prof. Tom Ottenhoff receives Eijkman Medal

Prof. Tom Ottenhoff (Leiden University Medical Center, Netherlands), partner in VacTrain, has been awarded the Eijkman Medal 2013 for his research on the immunology of leprosy and tuberculosis. The Eijkman Medal Foundation was established in 1923 in honour of Christiaan Eijkman, the 1929 Nobel price winner for Physiology and Medicine. Since its establishment, about 50 persons who have distinguished themselves in the field of tropical medical research and international health care have received the Eijkman Medal.

 


 

September 2013 - Promising unconventional malaria vaccine

A study team from the US has shown that a dose-dependent immunological threshold for establishing high-level protection against malaria can be achieved by intravenous administration of a vaccine candidate, composed of attenuated, aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. The vaccine formulation appeared safe in a small number of vaccinees and met regulatory standards for early phase clinical trials. The experimental vaccine which requires storage in liquid nitrogen protected 12 of 15 volunteers from malaria infection, but the study was limited by the non-infection of one of the six control individuals challenged. Further studies to determine whether protection can last for some months and whether there will be any protection against heterologous malaria strains are planned. Seder et al., Science 2013; 341:1359-65.

 


 

09 September 2013 - VacTrainees started e-learning

VacTrain offers its PhD students several e-learning modules to study and prepare themselves for the face-to-face courses of the Training Programme. In September and October, the VacTrainees will study a paper about Correlates of Protection with online content on Immunology and a paper about Vaccine Adjuvants with online content on Vaccinology and the Infectious Diseases Influenza and TB. The e-learning modules are generated by the Health Science e-Training Foundation.

 


 

18 July 2013 - All VacTrainee positions filled

All eleven VacTrainee positions have now been filled. The eleventh VacTrainee has been selected and will start working at Novartis, Siena, Italy on November 1. Seven VacTrainees have already started their research projects at their respective institutes.

 


 

  01 May 2013 - Ten VacTrainees selected

Ten of the eleven VacTrainees have been selected. Their names and project descriptions can be found at our webpage VacTrainees. The first VacTrainee started her research project today at the Vlaams Institute for Biotechnology (VIB) in Ghent, Belgium. 

 


 

  03 April 2013 - VacTrain Research and Training Advisory Committee

The VacTrain Research and Training Advisory Committee is complete. Prof. Pier Luigi Lopalco (chair), head of the Vaccine Preventable Disease Programme of the European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden. Prof. Paul-Henri Lambert of the Centre of Vaccinology in the Department of Pathology and Immunology at the University of Geneva, Switzerland, and Training work package leader of the EC-funded High Impact Project ADITEC. Prof. Han van den Bosch, professor in International Public Health at the Free University of Amsterdam, the Netherlands, and business developer specialized in vaccines. Prof. Mariagrazia Pizza, senior project leader of Novartis Vaccines and Diagnostics in Siena, Italy. Prof. Luc Hessel, previous Executive Director of Policy Affairs Europe at Sanofi Parteur MSD, and independent expert on the development of new vaccines and the implementation of vaccination programmes.

 


 

March 2013 - Absence of efficacy new tuberculosis vaccine

A new vaccine, modified Vaccinia Ankara virus expressing antigen 85A (MVA85A), was designed to enhance the protective efficacy of BCG, the conventional vaccine against tuberculosis. A double-blind, randomised, placebo-controlled phase 2b trial using BCG vaccinated healthy infants was performed to test the safety and efficacy of MVA85A. MVA85A was well tolerated and induced modest cell-mediated immune responses. Reasons for the absence of MVA85A efficacy against tuberculosis or M tuberculosis infection in infants need further exploration. Tameris et al., The Lancet. 2013; 381:1021-28.

 


 

 28 January 2013 - Selection VacTrainees started

The FP7 multi-ITN project VacTrain, which officially started on 1 November 2012, has started their selection of eleven highly motivated and talented PhD students. These eleven VacTrainees will be selected out of 130 candidates through CV ranking, skype interviews and finally face-to-face interviews. You can no longer apply for one of the positions.

Funded by the EU under the FP7 Marie Curie Action - Grant number: 316655
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