Are we close to getting HIV vaccine?

The world celebrated HIV vaccine Awareness Day recently. And what a luck it was to land on Prof. Pontiano Kaleebu, the man who has been at the battlefront of HIV vaccine research internationally. He is currently the Director of the Uganda Virus Research Institute (UVRI), and Medical Research Council (MRC). Hilary Bainemigisha asked him whether the vaccine will come during our lifetime

How close are we, Professor?
It is a challenge to say. I can only say we are closer because we are understanding better the protective immune responses, he have a vaccine that showed some moderate protection in trials and we are basing on that and even on the other vaccines that failed, to improve on the new candidates we are trying out. There are also vaccine studies right now that are already showing early positive results in humans and these are going to move into the next phase of trials. Hopefully they will yield something. So, we are on track for a vaccine.

Would you give us a bold but realistic time frame? 10 years? 30?
I will hesitate to do that! Because throughout my 28 years of vaccine research, I have been asked this question and we always got it wrong! There is a time we were sure it would come in the next 10 years and it didn't! So now, we really don't want to commit on time periods

What challenges have you faced in those 28 years, holding a spear, in the science forest, hunting for the vaccine animal and not spearing any?
When I started vaccine development in 1989 during my PhD research in London, I was looking at the antibodies of Ugandans who were sick which we thought were the ones the vaccine would need. But in time, we realised that these specific antibodies were not protective. The challenge from the very beginning was that a vaccine tries to mimic nature. But there are no people recovering from the disease for us to study their immune system like it was in developing other vaccines such as measles and small pox. HIV kills its host so there is no natural response to replicate. Where nature is failing, it must be tough for man to reproduce the immune response

Secondly, HIV mutates so much more than any virus we know of. Even within one individual, it keeps on changing and now we even have viruses that are recombinants. It is so diverse

Thirdly, we don't have a very good animal model. Apes and chimps are close but vaccines that have worked in these have failed in humans. Maybe these are not the best models

Other challenges are limited funding which disable us from having the critical mass to bring the best technology, best scientists, good labs, etc because HIV vaccine research needs technology. Good scientists need better pay and better infrastructure.

Lack of funding keeps us at the stage where we have to use products that have been designed elsewhere. We cannot get involved in upstream research of designing the vaccines themselves! They think that is too complicated for us because we don't have the capacity. If we want to be at the forefront of research, some of the funding should come from Africa. The problem with the funding from the North is that they give us money and want to lead and this, sometimes, means that some of our scientists work as spanner boys, who develop samples, specimens and data not for use but to hand over to the North. That really annoys me.

How about volunteers for the studies?
Interestingly, we have never had a shortage of volunteers! That is partly because we do a lot of community engagement. There are many countries where research has failed because of lack of volunteers. If you go wrong in community engagement, it may destroy your research. You must follow international standards in ethics, information exchange and partnerships where the communities feel like partners.

So, would you then rate Uganda as excellent in Africa?
Oh yes, there is no study I can remember where we are challenged on being unethical or where we violated international standards.

How about corruption? Hasn't it affected research?
That is one thing I am proud of in our HIV vaccine research. Our research has been so transparent with proper accountability. International funders can pull out because of mistrust and that way, corrupt people can destroy our research, people's careers, future and reputation. Our capacity to manage grants have even improved over time. I have heard problems in other areas like Global Fund and the rest but within the research family, I haven't heard any embarrassing issues.

Uganda used to be the master of HIV research but now South Africa is taking over
True. South Africa has taken lead because their HIV epidemic is very high. In Uganda, we look for key populations at risk to do our studies while in South Africa, they just look at the general populations. Their Government has also invested a lot in research, they have good programmes, their universities are very well funded, they have good labs, more trained people and, so, their HIV research ecosystem is good.

But South Africa has HIV subtype C; if we get a vaccine against C will it work in East Africa which has A and D?
Of course that is a worry. We need to advocate for studies in Uganda and vaccine designs based on our sub type in East Africa. Many of the vaccine designs in trials are either C or B which is common in Europe and US.

What should we expect in the next 5 or 10 years?
We are excitedly looking forward to the results of trials going on in South Africa, and the new ones that are being started in East Africa, including here in Uganda. Another excitement is the new innovation of passive antibodies. We are waiting to see how successful they will be in stopping HIV infection

What are the trials going on in Uganda?
Currently, none but at least 2 that I know of are planned - I'm involved in both. One is an efficacy trial, the largest we are going to conduct to see if a DNA plus a protein can prevent HIV infection and another in Masaka that will use Mosaic and conserved antigens. We are also discussing with the Gates Foundation to see how we can participate in the passive immunisation study. Hopefully, UVRI and Makerere will be part of this study

If these trials on passive vaccine work, when shall the common person get the vaccine?
Luckily, we are a global village. We had a meeting in WHO recently to discuss regulation and access. It will be unethical to conduct studies in Africa and get a vaccine only for it to be out of range for Africans. The next step will be access. So if the vaccines studied are effective, it will not take long before they are available. For example, the first study that will give us results in South Africa will be like in 2020. But even if they are positive, we don't base on one study; we shall wait for the one here, which will take longer because we are starting with Phase one. This could take us another 3 to 4 years to 2024. Before then, discussions of accessibility will have begun. At WHO, we discussed how to bring in the large pharmaceutical companies, which have the capacity to produce a lot very fast. We have India and Brazil that can be supported to manufacture for low income countries. Funding bodies will support pharmaceuticals that supply low income countries.

I'm looking at the vaccine arriving in Uganda! Who gets it first? Definitely the rich and the connected
Not really! Through the public health, Government can say: where is the biggest epidemic? They identify areas of very high HIV. If you want to be effective you go to populations where the transmission is highest, like discordant couples, people in high risk careers, fishermen, etc. Then through the private sector, anyone can purchase the vaccine. If you are going for a long journey and you don't know if you can abstain, you pass by a clinic and they give you a jab so that you can have a peaceful journey.

Any message on HIV awareness day?
To eliminate the virus, a vaccine is very important. We have drugs of course but they don't cure. A cure and a vaccine are the two major scientific goals everyone is looking forward to. Combination prevention is very important but in a longer run, a vaccine will be the solution. So, community engagement has to be sustained. We have new people with unique challenges, new issues like treatment. How do you pitch prevention in terms of treatment? Adolescents are more exposed now to new risk factors. We need to look at challenges and sustain what we have done well.

Finally, I want to thank the media for the interest they have kept. The vaccine story is so long a journey, with ups and downs and if the when is not answered, people lose interest. But you have kept with us and we are grateful. As scientists, when we have mobilisers and supporters like you around us, it gives us encouragement. I also thank communities we have worked with. It has been a long journey. From the time when many people were dying; we lost friends, colleagues, staff, relatives, etc. The HIV fight has been an effort of everyone; researchers, donors, volunteers, the press, everyone. We are certainly happier now because we are no longer burying our children and very young people. But we need to continue until we have the vaccine and the cure.