About HIV and HIV Vaccines
There were an estimated 7,400 new HIV infections EACH DAY in
2008, and 33.4M people living with HIV worldwide.
Effective treatment for HIV has been available since 1996
and today the life expectancy of those who are HIV-positive and
receiving treatment is generally very similar to those who are
uninfected In UK, the number of new infections diagnosed every
week is roughly equal to the number put on
treatment. This means the overall number living with HIV is
growing each year. At present there are 200,000 individuals in the
US in need of treatment who are unable to access it and who are on
waiting lists, because of lack of funds and this is going to become
an increasing problem. Providing treatment in countries that have
limited resources is even more challenging.
We know that when used consistently, condoms can prevent the
transmission of HIV, and that circumcision reduces the risk of a
man catching HIV from a woman by roughly half. Despite very active
campaigning for their use, these two methods have not controlled
the rate of new infections, so we need to find new ways to prevent
HIV. Vaccines and microbicides are two possibilities.
Vaccines (also known as immunogens) often work by
mimicking the bug that cause infections and the idea is that
once vaccinated, people make a response (known as an immune
response) that protects them if and when they encounter the real
infection. These responses are divided into two types:
cells and antibodies. Both are
We don’t have a vaccine for HIV yet, even though we have been
trying to make one ever since the virus was first identified.
Designing a vaccine for HIV has been complicated by the
fact that we don’t yet understand which immune responses are
the most important for controlling infection. If we knew this we
could just focus our attention on these ones. We have learned
some important lessons from the rare individuals who
naturally control their infections- and progress very slowly
to full blown AIDS after becoming infected.
Scientists have come up with several ideas for an HIV vaccine.
Initially the focus was to stimulate antibodies by using a copy of
one of the surface proteins on HIV. VaxGen made it all the way
through the early trials and was tested in two large trials to see
if it worked. Unfortunately it didn’t. Attention shifted to
stimulating HIV-specific cells, and a disabled strain of a common
cold virus (adenovirus) was used as a carrier (or vector) for a
copy of a protein from the core of HIV. V520, as it was
known, also made it all the way through to test for efficacy in the
STEP and Phambili trials. These were stopped early because there
was no evidence that the vaccines were working, and because the
early results suggested the vaccine might actually increase the
risk of catching HIV. After thorough investigations, the most
likely explanation was that there was no effect and no harm.
Last year saw the completion of a very large efficacy trial
involving over 16000 volunteers which combined these two strategies
and provided the first indications that it might one day be
possible to make an effective vaccine. RV144 (which was carried out
in Thailand) compared a vaccine consisting of a disabled bird virus
carrying core proteins, together with a copy of one of the surface
proteins from HIV with a dummy vaccine (known as placebo). RV144
reported that those that received the test vaccine had 31% less
chance of catching HIV compared to those that received the dummy
vaccine. Whilst not good enough to roll out, it was a good enough
result to carry on further with this ’combined’ approach.
What have we been doing in UK?
We have been working on vaccines for the past 15 years and also
started by concentrating on generating antibody responses to HIV.
We isolated an interesting strain of HIV to work with and tested
this with two novel adjuvants. An adjuvant is something which is
injected at the same time as a vaccine and which amplifies the
immune response which arises, by activating key components of
the immune system. In the trial, known as V001, we
saw very high levels of antibody – as high as those in
individuals infected with HIV – but unfortunately these could not
‘neutralise’ the types of HIV that had come directly from patients.
Scientists think that this will be an important feature of any
effective vaccine. We learnt that the quality of an antibody
responses is as important as the magnitutude. The adjuvants that we
used were developed further, and are now used with licensed
vaccines such as cervarix which is used to prevent infection with
the virus that causes cervical cancer.
The next step was to try and stimulate cells. We combined a DNA
prime ( the instructions for making the protein) with a boost
consisting of a disabled pox virus vector carrying the copy of the
same HIV proteins. This happened in two different collaborations,
one with the International AIDS Vaccine Initiative (IAVI) and the
MRC Human Immunology Unit in Oxford, and the second in a
pan-European collaboration called EuroVac. We completed 4 trials:
ICOX (IAVI 006), EV01, EV02 and EV03. The most
recent, EV03 was completed with the French agency for research into
HIV (ANRS) and involved clinical centres in France, Switzerland and
Germany as well as UK.
From these trials we have learnt that the DNA/pox combination is
particularly good at stimulating a cellular response, particularly
to viral surface proteins, provided that we use a sufficient dose
of DNA. We also learned that giving DNA three times was more
likely to broaden the response so that it also recognises core
proteins from the virus - which is thought to be important.
Unfortunately, the combinations of vaccines that we used in these
studies only generated weak antibody responses and we think
that both cells and antibodies are needed.
What are we doing now?
It will not be a surprise to know that we want to build on the
successful result of the RV144 trial and use the same kind of
“combined approach” - generating both cells and antibodies which
can attack the HIV virus. The UK HIV Vaccine Consortium (UKHVC)
brings together all the groups in UK working on HIV vaccines and
makes the best use of all their resources and expertise. This
academic consortium has been co-ordinating the manufacture of
batches of novel vaccines which we predict to be better at
generating antibodies and T- cells than anything that we have
tested before. We now want to build on what we have learned from
previous trials and to try out a new combination of products in
healthy volunteers as soon as possible.