News from the vaccine world

News from the vaccine world

Narcolepsy, an unexpected adverse effect of influenza vaccination, by Ben Van der Zeijst

Blog VacTrainPosted by Ben van der Zeijst 29 Oct, 2015 22:55

After the declaration by WHO on 11 June 2009 of an influenza pandemic, caused by an H1N1 variant, large scale vaccination was undertaken. There is a special European procedure for the development and licensing of influenza vaccines. A so-called mock up dossier is prepared using one influenza strain; later this strain is replaced by more relevant strain. Limited clinical trials are carried out to determine safety and efficacy, but these trials are not large enough to detect very rare adverse effects. The adverse effect narcolepsy in children due to the vaccine Pandemrix came as a big surprise. Narcolepsy is a naturally occurring disease affecting about 1 in 2000 persons. The symptoms are sudden periods of uncontrolled sleep and cataplexy, a short period of muscle weakness. The disease makes a normal life difficult and can be dangerous in traffic situations. There is no real cure. The cause is degeneration of a group of nerve cells in the hypothalamus that secrete hypocretin, a hormone involved in the control of waking and sleeping.

Last week I attended an expert meeting in Geneva organized by the IABS and the WHO.

The purpose of the meeting was to look back and evaluate, also in the knowledge that there will be future outbreaks of infectious diseases that require urgent mass vaccination with vaccines that not have been tested in large cohorts.

The narcolepsy case is a true detective story with initial doubts that vaccination had anything to do with the disease, very difficult epidemiology due to the low incidence and genetic predisposition for subject carrying the HLA-DQB1*0602 allele, the effect of media attention on reported disease incidence and false research clues from a retracted paper.

The first signals for a correlation between vaccination with Pandremix and narcolepsy came from Finland in August 2010, but it took a long time before this correlation was validated. In Finland 1:16,000 vaccinated 4 to 19 years old developed narcolepsy. Vaccination in Finland was stopped in September 2010. In populations with less genetic predisposition the incidence was lower. In retrospect about 1300 cases of vaccine-associated narcolepsy were identified among 30.5 million vaccinated persons. How narcolepsy is caused is not yet know. The finding of protein homology between viral proteins en hypocretin and the hypocretin receptor has led to a hypothesis for autoimmunity, but this has not been proven. Work is going on to find the exact cause.

Lessons learned were:
1. Adverse effects should be actively monitored and quickly available for validation. This requires better Europe wide monitoring.
2. Signals should be validated faster; it took years before the causality was established.
3. When mass vaccination is carried out against (potentially) serious diseases with new vaccines rare and unknown safety problems may pop up.
4. If this happens real time benefit-risk analysis should be in place to decide to continue with vaccination or to stop.
5. Longer and broadly protecting influenza vaccines are urgently needed. This would reduce the need for frequent immunization and the connected adverse effects.

We have a vaccine against Ebola disease! By Ben van der Zeijst

Blog VacTrainPosted by Ben van der Zeijst 31 Jul, 2015 21:39

We are now almost a year and a half into a severe epidemic in West Africa caused by Ebola virus with a total of 27,748 cases and 11,294 deaths (41%) until July 26 2015.

Celebrations in Liberia after becoming Ebola free in May 2015. A couple
of new cases resurfaced 7 weeks later.

This outbreak could have been prevented if a vaccine had been available. But since 1976, the year of the first outbreak of Ebola virus in the Democratic Republic of Congo, no vaccine has been developed, although there were no scientific and technical barriers. There are two main reasons for that. 1. Until 2013 there were several new outbreaks, due to contact with monkeys and fruit bats carrying the virus, but they were always contained because communities understood that the disease is transmissible and can be controlled by hygiene and isolation. In total 2387 cases and 1590 deaths (67%) were recorded between 1976 and 2013 . 2. During these 37 years attempts were made to develop a vaccine and many prototype vaccines were developed using seven different vaccine platforms. Eight vaccines were even tested in primates, the best model for man . But further development was not undertaken, mainly because of the high costs (several 100 millions of €) to develop a licensed vaccine. For the pharmaceutical industry this would have been a project without return on investment and there were no public or other parties feeling the need to act. But after more than 2000 fatalities and the chance of an explosive increase something had to be done. The WHO convened an urgent meeting in which the two most promising vaccine candidates were selected for further development. Both vaccines already showed promising results in monkeys, the best model for man. Both vaccines are based on the Ebola virus glycoprotein G but have different expression systems . Phase 1 clinical trials were carried out and showed that the two vaccines are safe for humans, meaning that phase 2/3 studies to measure the efficacy of the vaccines could start.

Today the results for one of the two vaccines, developed by the Public Health Agency of Canada and produced by Merck became available. The vaccine appears to be highly effective. The Guardian reports . Full scientific details as described in The Lancet can be found as a link in this article.

Being in the Flow, by Ioanna Christopoulou

Blog VacTrainPosted by Ben van der Zeijst 22 Jan, 2015 12:15

Being a PhD student is not always easy. Long hours in the lab, frustration when experiments do not have the expected outcome, anxiety trying to meet deadlines for abstracts, papers, meetings, reports. But it is not all bad; there are many wonderful moments that should be cherished.

When I got the opportunity to assist as a volunteer in Cell-VIB-Symposium: The Multifaceted Roles of Type 2 Immunity Conference I did not think twice. My main task would be to help at the registration desk and the Q&A sessions and at the same time I could attend the presentations and poster sessions.

My anticipation was building up until the first day of the symposium arrived. Waiting at the reception for all the delegates to arrive I could not help but noticing everybody’s excitement. They will wait for their badge, while taking a final look at the program before entering the room to follow the presentations (also asking questions about the picturesque city of Bruges). A mixed audience, as in any conference, ranging from early stage researchers, PhD students like I, to well-established scientists. One thing all having in common, their love for science and passion for their work.

For these three days, I was part of a buzzing community, eager to discuss and exchange results, and form collaborations. Through lively discussion both at oral and poster presentations I learnt a lot about different immunology aspects which gave me ideas for my own research. To my surprise, the author workshop as mentioned to the program, was an insight into the unknown world of scientific journals, with the participation of two Cell editors answering questions for their peer review/publishing procedure giving hints on how to have a successful outcome to your paper submission. An advice that one should always remember; fight for your paper and rebut a negative response if you truly believe in your research.

Good Science requires good Communication! by Mariateresa Coppola

Blog VacTrainPosted by Ben van der Zeijst 21 Nov, 2014 08:50

As young researchers, we really need to communicate our ideas and results to an audience effectively, using articles, posters and oral presentations; moreover, since we are all involved in the development of new vaccines, we should also be able to inform and discuss our work with a broad audience, since it’s clear that the successful story of a vaccine is linked to the number of vaccinated people.

Probably, we would all agree that “communication” is not a skill that is easy to improve when you are sitting alone in front of a computer. However when you test your abilities with other people and receive constructive criticism from them, you can start reflecting upon what you are learning and reshaping your ideas about the way you present your work.

For this reason I was really enthusiastic to join the course “Communication in Science” for PhD students, organized in Leiden. It consisted of 5 sessions in which we (the participants) experienced various forms of written and oral presentation from an interactional perspective, discussing and reviewing the work of others, giving and receiving feedback, commenting about posters, articles… it was worthwhile!

I learned a lot from the tutor and the other students but the most useful recommendation was: never forget the audience! In fact, generally we are focused on what we want to do, instead of what we want our audience to do as a result of reading what we wrote or listening to what we said. So since you are my audience and “effective communication uses information to move an audience from an initial mixed state of knowledge to a final state of understanding”( S. Benka), I would like to share two articles suggested during the course that may be useful for you in future:

· Stephen G. Benka. Who is listening? what do they hear? Physics Today 2008; 61, 49

· P.J. Sterk, K.F. Rabe. The joy of writing a paper Breathe 2008; 4: 224-232


ISSSI 2014 in Chicago, by Claudia Lindemann

Blog VacTrainPosted by Ben van der Zeijst 22 Sep, 2014 13:16

International Symposium of Staphylococci and Staphylococcal Infection

32 years ago scientist from all over the world started to meet biannually to present discuss progress in Staphylococcal research. This year the 16th symposium took place in Chicago, hosted by the University of Chicago. During the last three decades public interest in this field grew, in particular through the increased development of antibiotic resistance in Staphylococcus aureus and epidermis, and more than 300 delegates attended the conference. Through VacTrains support I was able to show my first poster to a scientific audience there.

The 4 day program covered a range of subjects including pathophysiology, “omics” (genomics, transcriptomics, proteomics, metabolomics), regulation as well as therapeutic and prophylactic interventions. Leading experts in their field gave an introduction in the morning, followed by talks given by experienced researchers and junior professors about cutting-edge results straight from the bench. Early-stage researchers were then given the chance to present in the afternoon poster sessions (more than 250 in just 4 days!).

“Vaccines against S. aureus disease” was the topic of Thursday morning, emphasizing the importance of this preventive approach. Some potential antigens as well as efficacy models were showcased and delegates from industry gave an update on clinical trial outcomes of vaccines in their pipelines.

In between presentations and talks, one was given plenty of opportunities to network with experts from industry and academia, talk to them over lunch, coffee or a gala dinner. Current issues and challenges were discussed and I gained a lot of inspiration and ideas for my own PhD project – which I could think about while discovering the vibrant metropolis the following weekend.

Lindau Nobel Laureate Meeting, by Benedict Halbroth

Blog VacTrainPosted by Ben van der Zeijst 17 Jul, 2014 09:31

During the first week of July, I took part in the 64th Lindau Nobel Laureate Meeting in Physiology and Medicine. The European Commission had supported my application to the Lindau Nobel Selection Committee, which then invited 20 Marie Curie fellows to this exceptional meeting. Located in the beautiful city of Lindau at the lake Bodensee (which is at the border of Germany, Switzerland, and Austria), 37 Nobel Laureates came together to meet young scientists from all over the world – including myself!

Taking part at the Lindau meeting was certainly one of the most exciting and inspiring events I have experienced so far: I had the opportunity to take part in science breakfasts, numerous lectures as well as several discussion sessions, each accompanied by at least one Nobel laureate. Furthermore, I had the opportunity to meet the laureates in person (e.g. Professor Arieh Warshel) during lunch and dinner events.

Most excitingly, Professor Zinkernagel had accepted me as one of four young scientists to give a presentation in his “master class” about pandemic diseases. This gave me the fantastic opportunity to present and discuss new approaches and ideas in vaccinology with about 70 young scientists as well as Professor Zinkernagel. Getting feedback from one of the most respected immunologists worldwide and discussing ideas with some of the brightest young researchers was most inspiring, gave me tremendous motivation to pursue my research, and strengthened my ambition to become an expert in vaccinology.

Some of the events during the Lindau meeting are published online (including all given lectures): Having a special interest in infectious diseases, cancer, and immunology, I was particularly pleased to have the opportunity to listen to Prof zur Hausen, Prof Zinkernagel, Prof Barré-Sinoussi, or Prof Peter Agre. But many other lectures were equally enjoyable and inspiring: For example, the 89 year old Professor Oliver Smithies emphasised his joy and passion for science and was very convincing that this is the very key to be successful in science!

I am very grateful to have had these fantastic experiences at the Lindau Nobel Laureate Meeting and would like to thank VacTrain, the European Commission, and the Lindau Committee for giving me this opportunity!

Picture/Credit: Christian Flemming/Lindau Nobel Laureate Meetings

Introduction to the blog

Blog VacTrainPosted by Ben van der Zeijst 03 Jun, 2014 12:41
In the 20th century between 300 and 500 million people died from smallpox, an infectious disease now eradicated by vaccination. Without vaccines there would be much more cases of infectious diseases everywhere in the world. But we need still more vaccines and some vaccines should be improved.
Look at the numbers (WHO, 2012):
HIV/AIDS:1.7 million deaths
Malaria:627 000 deaths
Tuberculosis:1.3 million deaths

Vaccine development is a long (about 16 years) and expensive (several 100 millions €) process. It is also a complicated process with several players. Universities, public research institutes and biotech companies are involved in early stage research (discovery). Often they continue to test vaccines in animals, providing proof of principle for efficacy and safety. Pharmaceutical companies usually carry out the clinical studies to test the vaccines and produce vaccines. Finally, government agencies decide whether the safety and efficacy of a vaccine is sufficient before admitting it to the market.

Almost everybody has come in contact with vaccines, but to improve vaccines and to develop new vaccines, vaccine specialists with knowledge on the entire process of vaccine development are needed. Therefore, we started ‘VacTrain’, an EU-funded training network consisting of 8 academic and industrial partners in vaccine research and development. VacTrain started in 2012. 11 young researchers are presently working on their PhD studies and are at the same time trained to become vaccinologists. In later blogs you will hear more from them. We will also update you on new developments from within the Vaccine World.

Authors: Dr. Wendy van Hemmen and Prof. Ben van der Zeijst