On this International Women’s day 2012 we would like to send
out special thanks to all the volunteers in Mucovac 2
by Sarah Joseph, posted on: 08 March 2012 at 15.00
The trial is going full steam ahead. As of this week, we are
approaching halfway - 13 women have been recruited into the trial
and things are going very well. It seems as though the rate of
recruitment is accelerating which is terrific news. Without healthy
volunteers like you, none of this research would be possible and we
appreciate your commitment very much.
It has been almost a year since I have updated my blog and I
can’t believe how the time has flown by. A lot has been happening
in the world of HIV vaccines. September 2011 saw the annual HIV
vaccine conference in Bangkok which is one of the main events in
the calendar for those working in the field. The location was
particularly relevant because some hotly anticipated results from
the RV144 were the highlight of the meeting. I mentioned the RV144
or “Thai trial” in my previous blog. The vaccine did not work well
enough to be taken further in its present form but the encouraging
results provided new impetus to the field and also, potentially,
clues as to how the vaccine might be having its effect. After
extensive analysis of the samples carried out in a spirit of
unprecedented collaboration, two of the responses made to the
vaccine turned out to be important in determining whether a
volunteer got infected with HIV (see below for more information).
The results are of particular interest to us because we are
currently in the final stages of planning two trials which follow a
similar vaccination strategy to the one used in RV144. The UKHVC003
trial will start later in 2012 in London and the Tamovac 01 trial
is already running in Tanzania and Mozambique. Based on our
previous results, we think that some responses that we will see to
the vaccines in these trials might be better than those seen in
RV144. We will have to wait and see whether the immune responses
which develop after vaccination are similar to those that showed a
relationship to protection from infection in the Thai trial. We
have no way of knowing whether this will be the case until we have
finished the trial.
More information on RV144
The samples collected during the trial which were available for
analysis were considered to be so precious that a call was put out
to scientists for help in the identification of immune responses
which might be playing a role in the protection observed. After
some preliminary analysis across a consortium led by Bart Haynes,
six different immune responses were prioritised and a “case
control” approach adopted for the analysis. Briefly, these six
responses were measured in samples from vaccine recipients who
became infected and compared to the same responses in those who did
not. Samples were taken at week 26, two weeks after the final
booster immunization. Ten infections occurred among vaccine
recipients prior to week 26, so the total number of infected
individuals that could be included in the case control study was
41. The total number of uninfected vaccine recipients included in
the comparison was 205. More information can be found here:
http://app2.capitalreach.com/esp1204/servlet/tc?c=10188&cn=aidsvac&s=20457&dp=player.jsp&e=16010&mediaType=slideVideo
Analysis revealed that two of the immune responses showed a
relationship with the risk of getting infected with the virus after
vaccination. Individuals whose blood contained a Y-shaped immune
molecule called an immunoglobulin G (IgG) antibody recognising a
portion of a HIV's outer envelope called the V2 loop were 43
percent less likely to become infected with HIV than subjects who
did not make these antibodies. Those making another kind of
antibody, called IgA, recognising different parts of the HIV
envelope, fared worse and they were 54 percent more likely to
become infected than people who did not make these antibodies, but
this immune response did not make people more susceptible to the
virus than trial participants who got a placebo. Bart Haynes was
keen to stress that the results were not definitive and should be
viewed more as useful for generating hypotheses for future study.
He commented "What we now have are clues as to why it might have
worked. That's something we haven't had over the past 30 years.
That's very important for the field."
More information on UKHVC003
UKHVC003 and is funded by the UKHVC (www.ukhvc.org) and the UK
Medical Research Council. One main objective of the trial is to
assess whether a course of 7 vaccinations (three injections with
DNA followed by two with a modified virus called MVA and two more
with a synthetic protein derived from the outside of the HIV viral
envelope) is safe and well tolerated and good at promoting antibody
responses to the vaccine. The other main objective of the study is
to see whether we can combine two of the vaccines and thereby
shorten the length of the course by 8 weeks without compromising
safety and potency. We suspect that shortening the course like this
might actually improve the potency of the vaccines. You can find
out more about the trial here:
http://www.ukhvc.org/2011/07/26/uk-hvc-announces-uk-hvc-spoke-003-trial-of-new-hiv-vaccine-candidates/
We hope to be able to tell you that the trial is open to
recruitment later this year. We are in the process of getting all
the regulatory approvals that are needed for a study of this kind.
As you know from the history of Mucovac 2, this can take longer
than anticipated.
Sarah Joseph
on behalf of everyone involved in Help Make History
Comments to: info@helpmakehistory.mrc.ac.uk
The best laid plans.....
by: Ken Legg posted
on: 16 November 2011 at 12.00
I know I shouldn’t be surprised when a plan
doesn’t come off but we never thought it would take nearly 18
months from when we launched the Help Make History website to when
the first trial actually started recruiting but I am really pleased
to be able to say that the first trial (Mucovac 2) is open! And you
should have received an e-mail if you can take part (sorry to all
the men but this one is for women only but there should be one in
the New Year for you)
It has been a long and at times frustrating
journey for all the people involved but with much relief and
excitement it is finally all systems go and the first of many HIV
vaccine trials planned over the next few years has opened.
Many things can cause a delay before a
clinical trial can start. We need to get approval from regulatory
authorities, the research ethics committee, the hospital the trial
is taking part in and all the departments involved (pharmacy,
laboratories, x-ray department etc) and contracts, insurance and
suitably trained staff at the sites must all be in place before we
start and then there is the vaccine.
A new vaccine takes many years of development
and testing before it can be given released for a trial and there
are many levels of quality control and stability testing on the
vaccines and inspections of production facilities before they can
be sent to the hospitals and these will continue after it has been
released, and why is?….. because the most important thing in any
clinical trial is the safety of the participants.
I have worked on several HIV vaccine trials in
the past and I am always amazed at the generosity of the people who
come forward to take part. They are aware of how important the need
is to find an effective vaccine and are willing to actually do
something to help find it and willingly give us their time (and
blood) to try and move one step closer to finding it.
I hope that once some of you are on the trial
you may be willing to write a blog about your thoughts and we can
publish it here to tell everyone else about your experience and
what motivated you to come forward, I think it may help others make
up their minds about taking part.
As we continue to learn, from previous trials,
about what works and what doesn’t we are able to focus on the
things that we know work and develop on these.
The next few years are key in our quest for a
vaccine as we develop trials that test new vaccines, different
products in the strategies that have shown to be most effective and
new innovative devises to deliver the vaccines - maybe one of these
will prove to be the trial that leads to something that really will
‘Help Make History’.
Comments to: info@helpmakehistory.mrc.ac.uk
Location, Location, Location
by: Ken Legg posted
on: 14 June 2011 at 16.00
For the last 12 years the Medical Research
Council’s Clinical Trials Unit has been next to Euston Square tube
station but in a couple of weeks it’s moving to a new location in
Holborn called Aviation House. The new offices are spread across 2
floors of large, open plan spaces - very different to the current
small office arrangement over 6 floors in 2 different
buildings.
There may be a few technical problems during
the move but hopefully it will all go smoothly and the website
should be functioning throughout.
Vaccnes have been in the news recently with
The Global Alliance on Vaccines and Immunisation asking the world
for £2.3billion to give life saving vaccinations to children and
save 4 million lives. Bill Gates is heavily involved in this
campaign and he and his wife are also very involved in the search
for an effective HIV vaccine.
So as you all will have noticed we still
haven’t started recruiting to any of our planned trials, we are
very close to starting but there have been several unexpected
delays with the first trial but I hope that very soon………
I am aware that the first people joined the
network almost a year ago and that things in your life may have
changed since then but hopefully you are still interested in taking
part in a trial or at the least still interested in how the search
for the first really effective HIV vaccine goes.
In the years ahead as the search goes on
hopefully there will be an HIV vaccine that can help to save even
more lives around the world so I ask if you can be patient and
don’t give up on the desire to Help Make History.
Comments to: info@helpmakehistory.mrc.ac.uk
Sarah Joseph
by: Sarah Joseph posted
on: 18 April 2011 at 17.00
I joined the MRC at the end of 2008 after
going back to college and taking an MSc in epidemiology
specifically so that I could work in HIV prevention. Over the
course of many of the preceding years, my work in the immunology of
infectious disease had provided me with the opportunity to live and
work in several different countries in Sub Saharan
Africa.
One of the main motivations for this change in
direction was witnessing first hand the devastating impact of the
HIV epidemic in communities already struggling against crippling
poverty. Young women are disproportionately affected by HIV and as
a result, the impact of the epidemic is compounded by the numbers
of AIDS orphans and children who are born infected.
Although I am very interested in all aspects
of HIV prevention, I focus mainly on vaccine development as this is
considered to be the most sustainable way of controlling the
epidemic. There has never been a more exciting time to be in the
field. After almost 25 years of disappointment, the results of the
“Thai”- RV144 trial in 2009 renewed faith in the prospect of an
effective vaccine.
The vaccine used in Thailand was only
partially effective and was not good enough for licensure, but the
results from the trial provided some insights into the kinds of
immune responses most likely to contribute towards protection.
Partly because of its’ integrated and collaborative nature, the
community has been able to respond very quickly to this progress in
the field and there are several clinical trials underway which hope
to capitalise directly on these very recent developments.
The MRC is part of two vaccine trial networks
active in Sub Saharan Africa and these joined forces last year and
are now working together on one such trial. Two components of this
potential vaccine have already shown great promise in Sweden and
Tanzania in trials carried out within the TaMoVac network which
brings together scientists from Tanzania, Germany, Mozambique, UK
and Sweden. The AfreVac network is made up of scientists from
Tanzania, Mozambique, UK, Holland, South Africa and Germany- some
of whom are common to both. By bringing the TaMoVac and AfreVacc
networks together, we hope to accelerate the development of a novel
vaccination strategy which will also be explored in parallel here
in London during 2012.
The vaccine regimen is quite complex and
involves the injection of three distinct components over the course
of about 6 months. It now seems most likely that the vaccines which
have been tried previously have not been potent enough and/or have
not stimulated the appropriate types of immune responses. The
results of the Thai trial suggested that a combination of three
such components might be particularly good at generating the
particular types of immune responses which are thought to
contribute to protection against infection.
In February of this year scientists hailing
from Mozambique, Tanzania, UK and South Africa and representing
both networks, met in Dar es Salaam for training in a new
laboratory technique which will speed up progress even more. Once
training is completed, it will be possible to carry out all the
most relevant analyses of samples from trial participants locally.
The vaccine trial is currently running at two sites in Tanzania and
will soon be recruiting in Mozambique too. That the sites in Mbeya,
Dar es Salaam and Maputo have established such capacity means that
apart from the obvious advantages, all the risks associated with
storing and shipping samples are kept to an absolute minimum. In
February of this year we found out that we have secured funding
from the MRC to carry out a similar trial here in London which is
very exciting.
The trial is planned to start in 2012 and will
probably recruit at one site in London. We are going to explore
ways in which a similar vaccination regimen to the one being tried
in Tanzania and Mozambique might be shortened hopefully without
jeopardising the potency of the vaccine. The length of the vaccine
schedule is seen as crucial to the long term feasibility of any
vaccine and every effort is made to keep the duration as short as
possible.
One of the most rewarding aspects of my work
has always been the opportunity to work closely with scientists
from all over the world. Conducting HIV vaccine trials in Africa is
not easy and we are very fortunate to be part of these committed
networks which are working towards the development of an effective
vaccine in the areas most affected by the epidemic.
Comments to: info@helpmakehistory.mrc.ac.uk
Three months already!……
by: Ken posted
on: 22 October 2010 at 17.00
So it has been exactly three months since we
launched the website and you may be wondering how it is all going
so I thought I would update you all. As the keeper of the site I
look almost every day to see how many people have looked at the
site the previous day and it makes interesting reading.
The registration page has been visited 562
times but currently there are only 25 people registered – 75% of
which are men. Not a bad return in terms of percentages but we hope
to get more in the coming weeks and around World AIDS Day in
December.
People from all over the world have visited
the site. The majority have been from the UK but we have been
visited by a total of 33 different countries from around the world
including Malaysia, Ethiopia, Costa Rica, Nepal, Argentina and
Latvia. Most people are on the site for about three and a half
minutes each time apart from the US were the 21 visitors spent an
average of 6 seconds on the site – wow, they must be fast
readers.
We have tried advertising in different places
from our usual locations, such as on the New Scientist website, in
Prospect magazine, on posters on tube stations and in a theatre,
some were more successful than others but the knowledge gained will
help direct future campaigns.
But what does this all mean in terms of the
success of the future trials? Well we aren’t quite on target
to get the 50 people registered in 4 months we originally estimated
but hopefully we will be close to it.
We do need to get more people registered on
the network – especially women as the first trial will only be open
to females.
So spread the word if you can and I am sure
that by the end of the year we will have enough women waiting to
start when the first trial is ready to go!
Comments to: info@helpmakehistory.mrc.ac.uk
Mitzy Gafos
by: Mitzy posted
on: 20 September 2010 at 16.00
I have worked in the field of HIV for 15 years
in various guises in the UK as well as internationally. As a social
scientist I am particularly interested in behavioural aspects of
HIV prevention and management. However, after many years of working
in East and Southern Africa, I fully recognise that ‘information’
and ‘behaviour change messages’ are simply not enough. Many women
either do not want to use condoms, sometimes as they want to
conceive, or are unable to negotiate condom use with their
partners. Because of these issues, women desperately need
additional HIV prevention options that they can use and that they
can choice whether or not to talk to their partners about.
For the last 6 years I worked in a rural part
of KwaZulu-Natal – the province most affected by HIV in South
Africa. My daily reality was that because I worked with a
predominately female team in their 20s 30s and 40s that
approximately a third of my colleagues lived with HIV. These were
smart and strong women – but introducing and maintaining condom use
was often just too challenging. Collectively we worked on a HIV
prevention trial called MDP 301. This was the largest
HIV-prevention clinical trial ever conducted in Africa and the
results were published in the Lancet today (Monday 20th
September).
We were only one of six research centres in
South Africa, Tanzania, Uganda and Zambia that enrolled over 9000
women into the study and worked closely with the local communities
to promote HIV prevention. Disappointingly the trial ruled out a
gel containing PRO 2000 as a potential microbicide as although it
was safe and proved to be highly acceptable to both women and men,
it did not reduce the risk of HIV infection when compared to a
placebo gel.
The results of the trial were first announced
in December 2009 as we wanted to make sure that the thousands of
women who participated in the trial were the first to find out the
results as soon as possible. However, today’s publication provides
extensive detail about the findings and shows that adherence to the
gel was very high and many women, who were unable to use condoms
for what ever reason, were willing and able to use a vaginal
microbicide.
In July of this year, results of another
microbicide trial finally provided the much awaited proof that a
vaginal gel can reduce the risk of HIV infection. The CAPRISA
(Centre for the AIDS Programme of Research In South Africa) 004
trial demonstrated that when used up to 12 hours before sex and up
to 12 hours after sex (called the BAT24 dosing regime) 1% tenofovir
gel reduced the risk of HIV infection by 39% and HSV-2 infection by
51%. This result is very exciting and brings a ray of hope for
women in need of additional HIV prevention options. However,
additional independent data corroborating safety and effectiveness
are necessary for regulatory approval and licensure before this HIV
anti-retroviral drug could be used in a vaginal gel for HIV
prevention. There are a number of ongoing and planned trials
that will aim to corroborate this finding and evaluate if the daily
use of tenofovir gel also reduces the risk of infection.
In MDP we want to build on the capacity and
expertise developed through the previous trial to swiftly implement
the MDP 302 trial. If funded, this trial will use the BAT24 dosing
regime but will also evaluate whether a single dose of tenofovir
gel used around the time of sex would still be safe and effective
against HIV infection. For me, it is critically important that we
evaluate this to ensure that we are providing a HIV prevention
option that is both convenient and cost-effective for women most in
need. If we find that a single dose of gel is as good as dual
dosing, then we would be able to put gel in the hands of twice as
many women!
Funders have committed millions of pounds to
microbicide development so far and it is crucial that this poor
economic climate does not prevent us from jumping the final hurdles
necessary to make vaginal microbicides available for the millions
of women desperately in need of additional HIV prevention options.
My last 6 years of work have left me in awe of the dedication and
commitment that women in areas of high risk of HIV demonstrate to
try to find additional ways to prevent infection – we can’t let
them down now – we have to make sure that we complete all the
research necessary to support making microbicides a reality!
Comments to: info@helpmakehistory.mrc.ac.uk
Team work
by: Sarah posted on: 23 August 2010 at
14.00
You’ll get to know more about me as I develop my blog, what
inspires me and why I love, despite its challenges, working in the
field of HIV research. As a person, I like to set myself the
challenge of doing something different every day that moves towards
an end result. Contributing.
The funny thing is that I received a school
book prize when I was sixteen called The Trials of Life
and now I am working in clinical trials, sort of by
chance.
I can’t stay to blog for too long as my role
of Scientific Research Administrator is a busy one, never mind what
I do in my free time. But there’s always time for all of us to do
more. Please therefore consider signing up to our network.
This week I am helping to promote, in Ken’s
absence, HelpMakeHistory around a play called ‘Elegies for
Angels, Punks and Raging Queens’ which is taking place at the
Shaw Theatre 10-28 Aug 2010 http://www.offwestend.com/index.php/plays/view/4525
do go to watch if you can, I’m sure it will be a very moving
experience.
What has struck me this week, is that to
tackle the issues that the world faces, everyone is or should be
working together, let’s help each other. All the disciplines are
coming together in the Shaw Theatre promo activity, from the IT
staff at MRC CTU who are helping me extricate the posters from the
printer to the taxi driver that will get me to the theatre with the
display boards, the director, cast and crew of the play, press,
audience…. the list goes on, and of course, my lovely team members
who are advising me on my poster design skills.
In short, it’s a team effort that you can be
part of, contributing to the making of history. It would be great
if you would consider signing up to our network and maybe becoming
a trial volunteer one day. If you need more information, please get
in touch.
More from me later.
Comments to: info@helpmakehistory.mrc.ac.uk
A week is a long time in
research
by: Ken posted
on: 29 July 2010 at 14.00
So after many months of preparation and
planning the helpmakehistory website was launched on the 19th of
July 2010.
For me it has been a very exciting and challenging project to be a
part of and I really do hope we are to build a network of like
minded people who want to do something to change how HIV is
affecting people around the world.
We have started promoting the site and have an advert in The
Ecologist and The New Statesman this month. We are also going to
have posters at tube stations and are using social networking
(Facebook and twitter) to also try and help attract people to the
website.
We picked that date to coincide with the start of the World AIDS
conference in Vienna.
The conference was a big success with over 19,000 people attending
from 197 countries around the world.
On the HIV prevention front the big news was
from the CAPRISA 004 study which was a microbicide study conducted
in South Africa where women inserted either a gel containing the
antiretroviral drug tenofovir or a placebo gel into their vagina
before and after they had sex.
There were 38 HIV infections in young women
taking tenofovir and 60 in those on placebo, which means the gel
was 39% more effective at preventing infection. This was the first
microbicide study to show what is called a statistically
significant result. We hope this will lead to more reseach into
microbicides and hopefully the MRC CTU will be involved.
To find out more information on the conference and the CAPRISA
study go to www.aidsmap.com.
If we are able to get enough people to
register on the helpmakehistory website we will be able to
recruit to any new microbicide trials as well as all the up and
coming vaccine studies. Then when the results of these studies are
presented at future conferences it will be because of you and you
really will have made a difference and changed the future of HIV
prevention.
If you have any comments or suggestions about the website we really
would welcome then, is there anything you were hoping to find here
we haven't thought of just let us know?
So please spread the word, send the Facebook
site to all your friends.
Thank you.
Ken
Comments to: info@helpmakehistory.mrc.ac.uk
Let’s get started…
by: Sheena posted on: 16 July 2010 at
15.00
Thank-you for dropping in!
I’ll start by telling you about Help Make History which we have
been planning since 2009. Our Holy Grail is a vaccine, microbicide
or drug to prevent HIV – the search to find one or all of these is
the ‘Make History’ part.
There are lots of challenges on the way – generating sufficient
funding in the first place, getting product through the
manufacturing hoops and completing the clinical trials in a timely
manner, just to mention a few. So here’s the ‘Help’ part. We
recently completed the HIV vaccine trial known as
EV03-ANRS Vacc20. This was a trial of a novel vaccine for
HIV and was carried out in healthy volunteers in several different
countries within Europe. We were really impressed with our
French colleagues who had a network of healthy volunteers
standing-by when they started recruitment to the trial which made
the process highly efficient. We talked to our friends in the
London, Oxford and York universities and the International AIDS
Vaccine Initiative (IAVI), who are working on prevention – mainly
for HIV, but also TB and malaria - and agreed that it would
be great to see if we could assemble a similar network of healthy
volunteers here in UK.
We are launching Help Make History now under the HIV prevention
umbrella because it coincides with the International AIDS Society
2010 conference in Vienna. At the moment we are particularly
focussing on HIV vaccines because we know there are at least 3
clinical trials which will start recruiting in London in the next
12 months.
I’m sure you have heard how successful the treatment for HIV is
now, and how far it has come. I’ve been privileged to see that
history in the making as I was a junior doctor at the Martha and
Luke clinic in West London in October 1986. Those of you around at
the time will recall the grim reaper and tombstone ads that were
rolled out to every doorstep and featured on TV etc. Well it was
grim for people living with HIV in 1986. That was the year we first
heard of AZT but success was short-term only. Dual therapy proved a
little better, but it was 1996 when triple therapy truly changed
the future for HIV positive individuals, and as time goes by the
fear of long term toxicity from the combination of drugs continues
to diminish. The treatment story shows how success is slow and
steady rather than being an “overnight sensation”, and I have no
doubt it will be the same story for prevention.
I do hope you will feel persuaded to join forces with us by
reading more, and/or registering on the network, but even if you
don’t thank-you for getting this far!
Comments to: info@helpmakehistory.mrc.ac.uk