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News from the vaccine world

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

Blog VacTrain Posted on 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:
Adverse effects should be actively
monitored and quickly available for validation. This requires better Europe
wide monitoring.
Signals should be validated faster;
it took years before the causality was established.
When mass vaccination is carried out
against (potentially) serious diseases with new vaccines rare and unknown
safety problems may pop up.
If this happens real time
benefit-risk analysis should be in place to decide to continue with vaccination
or to stop.
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 VacTrain Posted on 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

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 VacTrain Posted on 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 VacTrain Posted on 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:

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

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


ISSSI 2014 in Chicago, by Claudia Lindemann

Blog VacTrain Posted on 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

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 VacTrain Posted on 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
, Prof
, 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 VacTrain Posted on 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

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

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