AIDS Vaccine: Discussion with International Aids Vaccine Initiative.

The minutes of the previous meeting have been circulated; are there any matters arising? No. Are they agreed? Agreed.

I welcome two representatives of the International AIDS Vaccine Initiative: Dr. Frans van den Boom, vice president, country and regional programmes; and Ms Naomi Saelens, resource development specialist for Europe. I hope I have pronounced those names correctly. The aim of the IAVI is to develop a vaccine that prevents AIDS. It is a not for profit organisation that works with national governments, civil society organisations and research institutes worldwide. Its core work is testing candidate vaccines and conducting clinical studies. Oireachtas delegations have visited IAVI programmes in Kenya and Uganda in the past 12 months, including Deputy Rory O'Hanlon, a member of this committee.

The IAVI has recently had some encouraging results with the discovery of two new powerful antibodies to HIV. Separately, there have been extensive media reports in recent days regarding AIDS vaccine trials being carried out by other organisations in Thailand, which claim to have found a vaccine that is at least partly effective. Perhaps the representatives could comment on this.

Ireland has supported the IAVI since 2001 through its Irish Aid programme, contributing more than €25 million during that period. I ask Dr. van den Boom to make his presentation to the sub-committee and I will then open up the discussion to questions from the members. I thank Dr. van den Boom and Ms Saelens for coming before the committee today.

Dr. Frans van den Boom

I thank the committee for the invitation. I will give an update on the field of AIDS vaccination and our programme in particular in the context of the overall fight against HIV/AIDS.

I will start with the results of the Thai trial, because they are significant, and by explaining what types of vaccine are not being tested against HIV. The most effective vaccines we know — against diseases for which we currently have vaccines — are live attenuated vaccines, in which the virus is attenuated and delivered to people, and whole killed virus vaccines. These two approaches are not used for HIV because there is anxiety that the live attenuated virus will mutate into wild virus and infect people rather than protecting them. The approaches we have used so far are state of the art, scientifically speaking, but are not considered to be as effective as the live-attenuated and whole-killed approaches.

Before the Thai results we had a number of solid reasons to believe a vaccine was possible. First, with a live attenuated vaccine we can protect monkeys completely against SIV, a sister virus to HIV. People who become infected with initial high viral loads are able to bring down those viral loads and remain without symptoms for several years. There are a number of people in whom infection is controlled without treatment — the so-called long-term non-progressors — and there is a subset of people who are frequently exposed to HIV but do not get infected. Those were the indicators that an AIDS vaccine would be possible. The significance of the Thai results is that now we have proven that a vaccine — in this case, a combination vaccine — can protect people. It is 30% efficacious. Most likely, that is not enough to license it in Thailand. Additional studies will be done in the next couple of months but this was a very important result because it provides clues as to the mechanism of protection, to what differentiates the placebo group who became infected from the vaccinated group who became infected and what differentiates those who became infected from those who remained unaffected.

It will give us additional information on the immunological response needed as well as information to validate the animal models we have been using so far. One of the problems with HIV vaccine research has been that what works in mice does not necessarily work in monkeys and what works in monkeys does not necessarily work in humans. For many other vaccines there is a valid animal model and, therefore, what is tested in animals is a fairly good predictor as to whether it would work in humans who do not have HIV. That is the significance of the Thai trial.

The significance of the neutralising antibodies identified is that they are the two most potent broadly neutralising antibodies we have seen and identified since the identification of HIV. Only four broadly neutralising antibodies had been identified. These are two new ones and there will be more. I shall provide an update on the neutralising antibody consortium and how that came about but the two in question are broadly neutralising and, most important, are easily accessible. The other ones were captured by very complicated glucose structures which were very difficult to attach to the epitobe. In this case, it is a great deal easier to attach to the virus and that is an important finding.

The third important finding to be presented at the PERC conference today, or perhaps yesterday, is that if one takes replicating factors it is possible to protect non-human primates against HIV infection. There is much interesting and important news in the AIDS vaccine field. We can speak now of a sort of renaissance in vaccine research and development. In the past couple of years we have seen a number of disappointments but this year there has been much progress and investments are really starting to pay off.

Considering the broader picture, why do we need an AIDS vaccine? The broader picture, of course, is that for every two people who are put on treatment in developing countries there are five new infections. If we want to put an end to the epidemic of HIV we need to develop more effective tools than those we have used so far. Behavioural interventions are important, as is arms reduction but the course of the epidemic has shown that behavioural interventions alone are not enough to stop the course of the epidemic. Although at a global level people say that HIV is stabilising, in sub-Saharan Africa HIV is very much a generalised epidemic with a large number of infections still ongoing. Vaccination programmes come in addition to the rolling out of preventive interventions and treatment programmes. We must bring an end to, or lower, the incidence of new cases of HIV. UNAIDS has done some modelling studies on the cost of HIV in 2015 that show the cost of universal access would be approximately $150 million on an annual basis, which is not sustainable. As Michel Sidibé, the executive director of UNAIDS, said recently, we cannot be kept hostage by treatment. We realise we have to put people on treatment but if we do not stop infection and are not more effective in prevention we will never be able to reach the goal of universal access.

What distinguishes IAVI from other organisations that work on AIDS vaccines? First, we are the only organisation worldwide that focuses on AIDS vaccine development. Many organisations work on AIDS vaccines but they also work on other diseases. Second, since the beginning of the organisation, we have involved the countries in the south in the research and development process. When we started in 2001 many scientists said IAVI's approach was stupid, that it was not possible to do early-phase trials in developing countries. Neither the expertise nor the infrastructure was to be found and therefore it was much easier to do the work in Europe, the United States, Japan or Australia. When one wanted to do efficacy trials one could go then to the developing countries and do a large-scale trial. We said that was not a correct model that we felt we had to work in and with the developing countries from the very start. Deputy O'Hanlon was one of the Members of Parliament who visited the trial sites in Uganda and Kenya. We built first-class trial and laboratory capacity in one of the laboratories in Uganda which is now one of the six global reference laboratories. For us, it proved that if there is commitment and a will to build such capacity, it can be done. In total, approximately 700 local staff are employed working on AIDS vaccines in the developing world.

In those clinical research centres we have taken seven different vaccine candidates into clinical trials in the past couple of years. That is an achievement in itself. Nobody else in the field has been able to implement that kind of portfolio approach to AIDS vaccine development. We have built large cohorts in order to get a good idea of the epidemiology and the normal reference values in the populations of developing countries. One of the studies was what we call Protocol G. That protocol is implemented in 21 countries worldwide, most of them in the south. It focused on people who are called "elite controllers". They are infected but show no symptoms. It was in that population that we identified the two broadly neutralising antibodies. They come from one person living with HIV. The expectation is that in the next couple of months we will identify more broadly neutralising antibodies. The relevance of that protocol is that it was primarily implemented in the south, whereas most of the other studies are taking place in the north. One likes to have broadly neutralising antibodies that are genetically close to the kind of sub-type prevalent in a given country. This is a prime example of how developing and developed countries can work together in order to isolate and identify broadly neutralising antibodies. Ultimately, these are the kinds of efforts that are needed to get a vaccine to the populations that need them most.

The last thing I would like to mention is the IAVI model. We were the first public private partnership in global health. The rationale for that was very simple. HIV is a very complicated and complex virus and there is a huge need for a vaccine in developing countries. However, in those countries there is no market and no money. Therefore, if one combines a very complex scientific problem and no market there is very little incentive for the pharmaceutical industry.

There is a good deal of work going on in academia and some work going on in biotechnology and big pharma. We must identify the most promising leads, whether from academia, biotechnology or big pharma, and move forward those promising initiatives. That is what we have done in the past and what we continue to do and what we will continue to do in the future.

As the Chair indicated, Ireland has been a leader in supporting AIDS vaccine research and development, especially in its support of IAVI, the International AIDS Vaccine Initiative. As the Committee is aware, given the economic recession Ireland had to interrupt its support for IAVI for 2010. However, we hope the economic situation will improve quickly. We are confident and hopeful that once the economic situation improves Ireland will continue to support AIDS vaccine development because, ultimately, when it comes to HIV and AIDS we must think through the endgame. At this point many people are focussed on the short-term needs, including the distribution of treatment and prevention. However, if we do not focus on the end game we will never win the fight against this epidemic.

I will kick off the discussion with one quick question and then open it up to the members. Dr. van den Boom ended the presentation by diplomatically stating Ireland interrupted its funding. We have ceased funding for 2010 having provided €25 million since 2001. Will Dr. van den Boom provide an idea of the overall budget, from where the funding comes, how the initiative has been affected globally by the economic crisis, where the initiative finds itself and the percentage decrease in funding that has emerged?

Dr. Frans van den Boom

The economic crisis affects us very significantly. I will provide some more details later. Most funding for IAVI comes from governments and especially the international development corporation. AIDS vaccines are on the list of official ODA, overseas development aid, goals prepared by the OECD Development Assistance Committee. The UK and Ireland were the first two countries to support IAVI in early 2000, followed by the Netherlands, Denmark, Norway, Sweden, Canada and the USA. Later on the Basque Country and Spain joined. We also received funding from the EU for specific projects in east and south Africa.

The operating budget for 2009 was €102 million. Due to interrupted funding the 2009 budget will be closer to €80 million. We must down-size some of the critical programmes we have built up in recent years. We must also down-size some of the co-ordination and the capacity in developing countries because a gap of €20 million is very significant. In addition to the public sector, the largest private donor is the Bill and Melinda Gates Foundation which gave what was termed a challenge grant of €105 million in 2001. We will spend that money in the coming years.

There is other private sector funding and there are foundations and a small number of individuals who support IAVI. In addition to the case of Ireland we received notice recently from the Netherlands that it will interrupt funding for 2010. The same is the case for Denmark although this was an administrative glitch. Decisions are still pending from Sweden and Spain.

I thank Dr. van den Boom for the presentation. Since there is no market in the developing countries where the prevalence of AIDS is very severe, the service IAVI provides in developing and testing the vaccines is important. I hope the funding stream from Ireland can continue in the not too distant future. I am not entirely comfortable putting questions because we are not funding IAVI next year.

By all accounts we are not the only ones.

Yes, clearly other countries are finding it tough as well. Is the cut in funding $20 million or €20 million?

Dr. Frans van den Boom

It is US dollars.

A $20 million reduction in 2008 and 2009 is very severe and, naturally, the organisation is put to the pin of its collar in deciding which projects to reduce. There is much good work not being followed up and it must be tough for such people as Dr. van den Boom who lead these projects in these circumstances.

Dr. van den Boom stated that for every two people treated there are five newly infected. What is the position with regard to the gender balance? He also indicated that behavioural interventions are not effective. Who could do more as far as behaviour is concerned? Does this apply more to men or women? Is IAVI involved in behavioural intervention? Perhaps it is only involved in vaccines which, in itself, is a significant problem. How do women fare and are they worse off than men in this regard?

I refer to governmental support from developing countries and the countries in which IAVI operates. What support does IAVI receive in terms of financial and moral support from such countries? Is there praise for IAVI's interventions and the work it carries out? Do these countries help to build confidence and inspire IAVI to greater things? The last question that comes to mind relates to large-scale projects. How are those selected for the placebo and those who receive the vaccine chosen? Is this a difficult decision? I thank Dr. van den Boom for the presentation and I look forward to his response.

Dr. Frans van den Boom

I thank the Deputy for the excellent questions. On behavioural interventions, in the past eight years more than one in 1,000 people have been counselled as part of research efforts by IAVI. To build these cohorts and recruit volunteers, often it is the case that for every one volunteer one needs to screen approximately 15 to 20 people. In the past nine years more than one in 1,000 people have received voluntary counselling and testing. They are informed on a regular basis of the need for protection. They are provided with condoms etc. but still, in these very controlled circumstances, the number of infections one sees will decrease but will never reach zero. One reason for that is that, because of gender inequality, women are not always able to protect themselves. Epidemiologically speaking, especially in sub-Saharan Africa, the percentage of women who are infected is now 60%. About five or six years ago the ratio was 40% women and 60% men. It is becoming a feminised epidemic. In some regions such as Botswana and South Africa it is not uncommon that about half of the women in prenatal clinics are infected. These are young women with new infections. When we talk about a vaccine we also talk about future generations and protecting mothers and children.

If one has people in research circumstances and infections still take place, one can imagine the same kind of behavioural interventions are less effective in daily situations. It may be related to gender inequality, poverty, people engaging in transactional sex in order to survive, stigmatised or criminalised behaviour, men having sex with men, drug use, etc. There are many factors. One sees that infections continue to happen.

On the support from governments, we have always said we will not build stand-alone capacity. We will always build capacity and link it to an existing institution. In Uganda the programme is linked to the Ugandan Virus Research Institute and in Kenya it is linked to the Kenyatta National Hospital. We have always sought explicit support from governments, so governments support the beta vaccine in the countries concerned. We have facilitated the creation of national AIDS vaccine plans so that it is not an IAVI responsibility but that governments feel the responsibility to support and invest in the programme. Most countries need to provide political and moral, not financial, support.

We have a programme in India and the Indian Government is stepping up to the plate. The same is happening in South Africa. If one looks at newly industrialised countries such as China, Brazil, South Africa and India, they are also starting to invest in the development of an AIDS vaccine, which is very promising.

On the large-scale trials involving the placebo and vaccine groups, it is done at random. One person could be in the vaccine arm of the trial and I could be in the placebo arm, but we would not know. The groups are matched in terms of background characteristics, demographics etc. It is only at the very end of the study that the two groups are unblinded. For the Thai trial, it was only this year that the investigators knew who was in the placebo group and who was in the vaccine group. At that point, the number of infections in both groups of the study were compared.

I thank Dr. van den Boom for his presentation. I have some questions. The figures for the Thai trial were that the combined vaccine approach could lead to a cut of 31% in the number of HIV infections. It is not effective enough as a vaccine at this stage because at those levels it could encourage changes in sexual behaviour or drug users to change their behaviour and put themselves and others at risk. At what level of success does a vaccine become eligible to be put on the market? The $64,000 question is how long Mr. van den Boom thinks it will be before we reach those levels.

My second question concerns a statement made by a journalist regarding the conference. In regard to the vaccine she said the results of the study also hint that the vaccine may work better in the general population than in those at higher risk of infection, such as gay men and intravenous drug users. Is Dr. van den Boom aware of why there would be a difference regarding success? Is it connected to behavioural differences? It would be helpful if he could throw some light on that.

Dr. Frans van den Boom

The first question is really important because we have vaccines which have 60% effectiveness. Contrary to what a lot of people think, it is not the case that every vaccine has 100% effectiveness. One of the effects of a vaccine is the herd effect. If one vaccinates a population, one does not need a vaccine which protects 100% because when the larger part of a population is vaccinated and protected it will have an effect on the rest of the population.

We have never seen a vaccine which is 30% effective. At this point the Thai authorities will have a lot of discussion on what do with a 30% effective vaccine and whether to licence it. We have done some modelling and with a 30% effective vaccine which would be distributed to approximately 50% of the adult population, one could still avert 5.5 million infections by 2015. The question will be if we are confident enough to start producing the vaccine or if we will use the results of the vaccine to improve it so it has an effectiveness of 50% or more. At this point no one is discussing licencing the Thai vaccine.

One also has to keep in mind that this vaccine had to focus on two specific sub-types, B and E, so even if it was licenced it would be licenced for Thailand alone. One would have to do a number of additional studies in sub-Saharan Africa, India and China because the sub-types there are C, E and, in Tanzania, D.

The question on disinhibition is interesting. We do not have a lot of good data on that. If one has a partially effective vaccine, would it lead to more risky behaviour in people who protected themselves before they got vaccinated? We have some indications regarding treatment. If people have access to treatment it may have a disinhibition effect on safe behaviours. In the western world we have seen an increasing number of infections in men who have sex with men, MSM. The key message with a partially effective vaccine needs to be that people should not rely on the vaccine alone but should have a combination of preventive interventions to protect themselves.

On the high-risk populations, this trial was done in a heterosexual population which was not particularly high risk — the number of HIV infections in the study was quite low. The assumption that it might not work for IV drug users and men who have sex with men has to do with the fact that blood-to-blood transmission is much more effective than sexual transmission. It may be possible to protect against infection through sexual behaviour but it may not apply to blood transmission. With respect to MSM, it concerns inserted behaviour and the type of sexual behaviour which increases the probability of infection.

How long will it take to develop a vaccine? That is the million dollar or the million euro question. One cannot predict science. Somebody once said, "you fail once, you fail better and you succeed." In the next couple of years we will see several failures in AIDS vaccine research but we will also see a number of successes. Even if there was the absolute breakthrough tomorrow, it would take years to translate that scientific finding into a vaccine that can be manufactured and deployed on a global scale. It is a long-term effort. Everything about HIV-AIDS is long-term, whether it is treatment, prevention or the development of a vaccine. There is some modelling being done by the 2031 group whereby if one were to combine partially effective interventions, treatments as preventions, circumcision, microbicides, behavioural interventions, and harm reduction interventions and get them to the people who need it most, there would still be 1.2 million infections on an annual basis in 2015. Even if we succeeded in combining all of these interventions there would still be a compelling need to develop a vaccine.

I welcome the two witnesses to Ireland. Deputy Naughten and I visited Kenya and Uganda and were very impressed with the work they do there, preparing the candidates for the vaccine but also much other good work, including giving people the opportunity to be investigated for HIV and the investigation that diagnoses the management of HIV. Obviously the development of a vaccine is of key importance. It is recognised worldwide that prevention is better than cure and that a vaccine is the way forward in preventing HIV and AIDS into the future.

On the question of the host candidates for investigation of a vaccine, obviously there are good reasons these vaccines should be tested on a population where the disease is endemic rather than, say, in the western world where a vaccine may be discovered. In that context I wonder if, in respect of the new vaccine from the Scripps Institute in California, any arrangements have been made for clinical trials in Africa? Like my colleagues I would be concerned, although I understand the reason, that funding was suspended in Ireland in the current year and I would hope that is temporary and that it will not be long until we are in a position to support the good work done by the International AIDS Vaccine Initiative.

What is the incidence of HIV-AIDS in the countries in which the representatives work — five countries in Africa and Sub-Saharan Africa? If the incidence has increased or decreased, is there any particular reason?

Professor Frans van den Boom

I agree that prevention is better than a cure and prevention is better than treatment. We all know that vaccines have been the most cost effective public health intervention ever and the same will apply to the development of an AIDS vaccine but similarly to the development of a malaria vaccine or a TB vaccine. I thank the Deputy for the question on the Scripps Institute. That is a good illustration of the IAVI model. The immune system has two arms. One is called the neutralising antibody, and it recognises the virus before it infects the cell and neutralises the HIV. The other part is called cellular mediated immunity. The immune system recognises the cell that is infected by HIV and clears it. Many of the vaccine candidates that are in clinical trials focus on the cellular mediated arm of the immune system. The Thai vaccine was a prime boost which had a cell mediated component and a neutralising antibody component.

In 2002, when everybody focussed very much on CMI vaccines, we said one needs a very focused effort on neutralising antibodies because neutralising antibodies are absolutely essential for the development of a preventive vaccine. We created the Neutralising Antibody Consortium which brings together the best scientists around the world to develop neutralising antibody vaccines. That work brought people of different backgrounds together. One of the collaborators was Dennis Burton, who is the world expert on neutralising antibodies and was working at Scripps. At a certain point we entered a more formal agreement with Scripps to collaborate. All of these collaborations are governed by the fact that everybody has to sign up to an agreement on intellectual property; that is, once a vaccine is developed it has to be made available to the south within a reasonable timeline, at a reasonable cost and in reasonable quantities, all of which is specified in the contract.

We linked up with the Scripps Institute in a formal collaboration which was announced six weeks ago. Unfortunately, because of the budget problem we have to slow down some of the efforts on neutralising antibodies as well. The nice thing about the Scripps Institute and the Protocol G which is done in 21 developing countries is that it is a very smooth collaboration in which countries in the south and countries in the north work together and collaborate on developing neutralising antibody vaccines.

Where is it epidemic?

Professor Frans van den Boom

The important thing is that everybody has to know their epidemic. For example, in Uganda, the number of HIV infections among the younger population is going down, probably as a result of the information campaigns up to the last couple of years. What they found out is that it has shifted to the population in their 20s; when they enter stable relationships or get married they get infected. The number of infections is still very high. One might be fooled by looking at one population where the incidence was high but goes down. Then there is another wave in a somewhat different population or age group.

May I ask about that? Professor van den Boom made a comment earlier that some people have said there is a stabilisation in the rate of HIV-AIDS. We know Uganda fairly well, having been there last year. Our ambassador was here with us recently and those figures did arise. In certain parts of the population the rate is decreasing. Can Professor van den Boom give the committee an idea of the state of play generally as he sees the epidemic globally? How much worse has that got? Is there an element of stabilisation occurring?

Dr. Frans van den Boom

There is no disease so prevalent in developing countries about which we have so much information as HIV in terms of incidence, prevalence and the population groups. It is not easy to analyse or understand the numbers. In previous years we have seen the UNAIDS numbers go down in terms of HIV infections. I believe it was in 2004 that UNAIDS estimated there were 15 million new infections on an annual basis and its latest report indicated that the figure was closer to 7 million on an annual basis. The question is whether that is because our monitoring has become much better, the incidence is decreasing tremendously — by 50% on a global basis — or the reverse. Have some countries over estimated or under estimated the number of infections, for example, China? The numbers in China have increased tremendously in recent years and the question is whether that is due to better monitoring or because the Chinese were withholding information.

Is it not important, even from a funding standpoint, that there is clarity with regard to the rates and the trends? One would have a concern that some lawmakers or people who are effectively the keepers of the purse would decide this disease has stabilised and question the need to fund this at a greater level. A concern would arise with regard to the lack of clarity in that regard.

Dr. Frans van den Boom

It is a good point. If 7 million new infections occur every year it would be a fairly serious problem on hand. Even in the poorest part of the world that would be considered to be endemic. We must get that message across to the public but also to the representatives, the politicians. If we said there will be 7 million H1N1 infections and 10% of those people will die, the world's response would be significantly different and it has been significantly different because all of Europe prepared for an outbreak of H1N1 and the mortality and morbidity rate from that is much lower than that from HIV-AIDS. We must make the argument that 7 million infections is unacceptably high. The international community must take responsibility in that regard, and that includes the countries in the south.

Does any other member want to ask a question? I thank both representatives for attending. We have had personal experience in nine countries with the programmes we fund and it goes without saying that we understand the importance of the work the representatives do. I thank them both.

Is there any other business? The date of the next meeting is Thursday, 29 October, when the ambassador to Ethiopia will come before the sub-committee. If members could attend that meeting I would appreciate it.

The joint committee adjourned at 12.55 p.m. until 11.30 a.m. on Thursday, 29 October 2009.