Following last year’s positive result from an HIV vaccine
trial in Thailand
the Global HIV Vaccine Enterprise has issued a new scientific plan, calling for
a speeded-up effort to test new vaccine candidates in large trials.
Global HIV Vaccine Enterprise executive director Dr Alan Bernstein also
called for young scientists to get involved in the field of HIV vaccine
The plan, available for download at the Global HIV Vaccine
Enterprise website, outlines two key priorities: better integration of the
latest information from basic science and ongoing trials into new vaccine
studies, and better use of information from preclinical studies and from other
areas of scientific research.
to Dr Alan Bernstein, pictured above, about some of the priorities in the HIV vaccine field.
Following the failure of the adenovirus-based HIV vaccine
developed by Merck in 2007, there has been considerable debate about the future
of HIV vaccine research, with some pronouncing the field a dead-end, and others
calling for a back-to-basics approach to investigating how HIV interacts with
the immune system.
But the Global HIV Vaccine Enterprise says that as well as
more laboratory science, more trials in humans are needed if we are to answer
the fundamental questions still puzzling vaccine researchers.
One example of the sort of question that needs to be
answered is: which immune system changes after vaccination correlate with
protection against HIV, and do these changes indicate a mechanism by which the
immune system protects against HIV infection that can be exploited in future
The Thai trial of a two-vaccine regimen that reduced the
risk of HIV infection by 31% is still being analysed to determine what can be
learnt about the correlates of protection, with laboratories all over the world
currently examining samples provided by the trial sponsors.
Dr Bernstein is hopeful that the pipeline of promising
candidate vaccines will soon offer some serious follow-up candidates to the
vaccines tested in the Thai
trial and the STEP and
Phambili trials, but larger trials of promising candidates need to get
underway more quickly.
“We need to go from one phase 2b study every seven years to
something like one every year, so that we have the opportunity to incorporate
new findings into the design of studies.”
The Global HIV Vaccine Enterprise calls this process
“integrating iterative scientific enquiry with product development.”
This means quickly incorporating new information from
ongoing studies or failed studies into the design of new studies and trials
that are just getting underway. It also means sharing data more quickly and testing
a wider variety of vaccine approaches sooner in human efficacy trials.
“Trials are expensive – phase III trials cost at least $120
million over their lifetime. [Starting one each year] implies a ten to
fifty-fold increase in funding. So if there’s another breakthrough like the
Thai trial we may need more than a 50% increase in funding.”
However Dr Bernstein declined to say how much the Global HIV
Vaccine Enterprise needs in order to fully realise its plans.
The need for lots of new efficacy trials also implies the
need for a big investment in clinical trials infrastructure. Vaccine trials may
need to recruit tens of thousands of people to prove efficacy in the future,
especially if expanding treatment has a greater effect on transmission at the
same time as other prevention interventions are also reducing HIV incidence.
“Partnerships are needed between the developed and
developing world. The cost of building that trials capacity is a drop in the
ocean in comparison with paying for the drugs.”
“I don’t like dichotomous discussions, treatment or
prevention, short-term or long-term. If we’ve learnt anything about this
epidemic, it’s that it needs a long-term multifaceted approach. If we don’t implement
what we know works, we’re not going to control this disease.”
“Making efficient use of clinical trial sites, regardless of
prevention modality and funder, is going to be critical. Before we ask for more
resources we need to be very sure that we are using existing resources to
The Global HIV Vaccine Enterprise is also seeking to
mobilise new financial resources, and new research capacity.
“There are some countries that are doing very little in
terms of HIV vaccine research,” said Dr Bernstein, although he wouldn’t be
drawn into naming names. (Russia
is a notable absence, while vaccine research in some Asian countries is still
under-developed relative to the size of their science and technology sectors).
“I’m very pleased that China has created mega-science
initiatives, one of which is an HIV vaccine initiative, which is joining the
Global HIV Vaccine Enterprise. Europe is going
through a major re-organisation of science programming so I hope we can look
forward to useful discussions with the European Union about how to go forward.”
Responding to perceptions outside the HIV field that a
vaccine for the infection is impossible, Dr Bernstein said: “It’s as likely
that there will be a vaccine for HIV as drugs for Alzheimer’s or some types of
cancers. There are sound reasons to believe that we can get a vaccine.”
But the development of successful vaccines is likely to
depend on the renewal of the research workforce too. Dr Bernstein says that the
HIV vaccine field needs young scientists who have the ambition to make a career
in this area.
“Pasteur said that what every scientist wants is to make a
great discovery, to have it applauded by your peers and to benefit humanity. I
can’t think of a better field than HIV vaccine research [to fulfil these
needs]. It’s become apparent that because of the difficulty in developing a
vaccine, we’re going to need great scientists. For young scientists it’s a
The vast majority of Nobel Prize winners in the natural
sciences did the work that led to their prize before the age of 40, Dr
Bernstein points out.
“Young people have energy, the naivete to be a great
scientist, the openness to new ideas. Watson was 23 when he was doing the most
important work in biology, the discovery of the DNA double-helix, and he and
Crick wanted to beat the old guy, Linus Pauling.”
The HIV Vaccine Enterprise also wants to catalyse interest
in solving some of the problems inherent in making an HIV vaccine by reaching
out to other fields, such as systems biology and genomics.
“We rely on the immune system to do our work [when
making a vaccine]. When it works that’s
fantastic but when it doesn’t work, there’s an imperative to find out what’s
going on. There’s a very complex set of interactions and we need a deep
biological understanding of that complexity.”
There is a need to use computation and new developments in
networks theory to understand the relationships between millions of fragments
of information derived from studying vaccine responses, and the interactions
between HIV and the immune system.
New technologies also need to be exploited in the search for
“There’s good reason to think mucosal immunity is critical
in HIV transmission, but how do we monitor what’s going on in the mucosa
without invasive and impractical tissue sampling? Is there a non-invasive way
to imaging at the mucosal surface to tell us what’s going on during the very
earliest stages of infection? There’s been a revolution in imaging technology
and we should talking to the [imaging experts].”