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Exciting times for HIV vaccines, less exciting times for the virus

On International HIV Vaccine Awareness Day (the 18th May 2016) at the HIV Vaccine Trial Networks (HVTN) meeting, it was announced that for the first time in 7 years and the first time in Africa, a HIV phase 3 vaccine trial will be taking place. In addition to this the world’s first HIV antibody infusion trial started with its first South African participant in Soweto.

Slowly we seem to be completing a puzzle. Perhaps the most complicated one ever pieced together.

Science is a developing story. Every study, no matter how mundane, adds a puzzle piece to the picture. Sometimes it’s an edge piece, that forms the basis for studies to come and sometimes it’s a middle piece that doesn’t really help anyone at the time but will be imperative to complete the picture. In some cases though, in order to progress, scientists stop fitting in pieces to the main puzzle and start their own. This is a risk because the evidence is leading the field in a particular direction and this direction is fairly certain because multiple people have determined the same thing. Sometimes though, the risk of deviating is worth it. Risk shakes up the field; breaks down dogma and enforces flexibility. And that is what this trial could mean for HIV vaccinology.

I am beyond excited that we are having our first trial in seven years and I’m even more excited that it is happening in South Africa. Capacity building has happened over the last couple of years, allowing for South African clinicians and scientists to run these trials. This means much more opportunity for young scientists, collaborations, funding and all round focus. We are finally in the spotlight. The findings of trials always mean that interest in the field surges again. New ideas will be emerging from unexpected places.

The most recent vaccine trial regimen that showed any protection was the U.S. Military HIV Research Program-led RV144 clinical trial in Thailand completed in 2009. This regimen showed that protection was mediated by something we did not expect. All our data in the field up until that time suggested that antibodies (called broadly cross neutralizing antibodies) that could bind and coat lots of different HIV viruses (preventing entry into cells) would be our best shot at a vaccine. But protection (bear in mind it was only 31%) was achieved by antibodies that weren’t able to block infection of a cell. Instead they are able to bind to an already infected cell and call for backup. Other cells with the ability to secrete substances that pop the infected cell heed the call and come to destroy the infected. Think of the broadly cross-neutralizing antibody as Batman (pretty capable

robin batman 1
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of a fight on his own) and these other antibodies as Robin. The vaccine was tested in Thai people who have a very different epidemic to the part of the world that bears the greatest burden, Southern Africa. So the HVTN has run a series of small trials in South Africans using a vaccine that would be more appropriate for our situation. And now, we are paving the way to HVTN 702 (not to be confused with the talk radio station); the phase 3 trial guaranteed to rock the boat of science.

 

A phase 3 trial is a big deal. A wide range of criteria need to be fulfilled in order to proceed to one and the criteria that were set for HVTN 702 have all been met. However there is much talk in the field that we are progressing for progress’s sake. Many feel like we are creating a vaccine that has both arms tied behind its back and we are expecting it to win an arm wrestling contest. We are expecting robin to win Batman’s fight.  We are pushing a vaccine through that does not create the antibodies we know are going to protect people and are based on historically unimpressive antibodies. Should we be doing trials on things we know are not optimal or should we take the risk and acknowledge that there are clearly things we do not understand? Perhaps what now seems like an arbitrary puzzle piece will start off a new and exciting puzzle.

hero sidekick5400 South Africans will be enrolled from November 2016 and we will know the outcome by 2020. It’s a long time to spend on something that may not work again. What would going back to the drawing board mean for new infections? The bottom line is we have not yet managed to summon Batman to fight for our cause. We have lots of ideas on how to get him there but so far nothing has worked. Should we give up on Robin just because he is not what we expected?

Most vaccines have taken between 25-50 years to develop, so technically 30 years in, we aren’t doing too badly: we have drugs that are very effective at keeping AIDS patients well, which our government has now pledged to provide free of charge to everyone infected; we have drugs that can be used to prevent infection (pre-exposure prophylaxis) and we have lots of ideas bout what will protect people in a vaccine setting.

For me, the proof will be in the pudding. By 2020 we may have even brighter ideas about what we need and how to get there. And potentially the pessimistic view of the current phase 3 if irrelevant if it goes on to form new dogma. If all this phase 3 trial does is encourage bright and motivated young people to tackle arguably one of the most perplexing problems the world has, it will be a win. Either way, now is not a good time to be HIV.

Posted on by Odi · 2 Comments

A Social Scientist’s Lab

When I think of a laboratory, it conjures images of pipettes and burners with complex mathematical equations written on a board. My laboratory, however, as a political scientist, has little to do with Bunsen burners and more do with measuring political heat. Very few people, outside the social sciences, understand how social science research is conducted and often liken it to tea leaf reading.

Research in the social science, particularly in politics and international relations, is really dynamic. There is an adage that ‘a week is a long time in politics’. A political leader can move from a hero to a villain and back again within a few days. Because of this dynamism, the work of the social scientist is important because their job is not only to analyse current state of affairs but also pick up on issues that could be arising soon. The social scientist should be able to direct policymakers to areas that that need attention and draw in the expertise other disciplines to meet the societal need.

Conducting social sciences is further complicated by the plethora of techniques and approaches to draw from. A number of analysts prefer more traditional quantitative approaches that they ‘borrow’ from the natural sciences. Alternatively, they may decide to use more qualitative approaches. I fall in the school of thought that purely scientific approaches are not always appropriate to examine social issues. For instance, research into political psychology would require a more experimental approach to political science but examining government decision-making needs a more holistic view. If you think about it, statistics presents a state of affairs but can’t help you predict how a leader, or government would respond to that state of affairs. There are so many  structural and relational power dynamics that affect decision making that statistics can only be a part of the overall picture. The only way to fully understand, and to an extent predict, possible future scenarios, is to understand the internal and external environment that  guide governmental and political decision-making. This exploration has to make use of international legal instruments, historical decisions making and being able to read shifts in the social environment.

The political scientist also has to draw on important skills that can’t be taught in a lecture hall, such as relationship building and listening skills. Listening goes beyond hearing what is said but includes being able to pick up to what the speaker is truly trying to convey. Many times, as it is with politicians and bureaucrats. The words that they use often have dual meaning or are a signal of something larger. A gruesome example is from the 1994 Rwanda genocide, there was a lot of rhetoric in the media about cockroaches needing to be exterminated. Tapping into relationship networks and listening carefully helps social scientists do their jobs better which can help, in some instances, save lives.

So what does my dream political science and international relations ‘laboratory’ look like? Aesthetically, it would be a cross between Olivia Pope’s apartment and office on the hit TV Show Scandal; basically it would be the love-child of comfort and function. The bookshelves would contain archive material, policy documents, newspapers and transcripts of interviews with experts in my field as well as others related to my subject matter. The living room would have a smart TV that would allow me to access the Internet as well as be linked to news sites around the world. The beauty of a smart TV is that is also does away with the need for a phone because communication is possible via Internet call applications such as Skype. There would also be a blue-tooth enabled keyboard so that I can type from the comfort of my couch when I need to. The only non-negotiable item that I would like is a feature wall with a magnetic glass white board. I prefer glass to regular white boards because they are easier to keep clean and, importantly, they are difficult to photograph. I often use paper or a white board to sketch my ideas or plot out concept relationships so having a stylish whiteboard would be great. Though, I must mention that I recently discovered new mind-mapping software that actually helps with mapping out key ideas (I plan on writing a review once I have fully mastered the program).

Ultimately, I don’t believe that your best social, or political, analysis comes from solely from facts and figures but also requires a good amount of intuition … and a comfy chair to sit on whilst you write.