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February 13, 2018

Scientist Joao Aguiar Pursues Malaria Vaccine

An interview with CAMRIS employee Dr. João Aguiar, a scientist and leader in the effort to develop a malaria vaccine.  Dr. Aguiar has been working for CAMRIS since 2011 and provides support to the Navy Medical Research Center (NMRC).  

CAMRIS:   What do you do for CAMRIS?

João: I work on malaria vaccine development. The work that I do – and I’ve been doing this for almost throughout my career – is to look for new antigens, a new malaria vaccine. 

The Gates Foundation about 14 years ago started to invest a lot in vaccines for tropical diseases, especially malaria – so did the National Institutes of Health (NIH), the U.S. Agency for International Development (USAID), and the U.S. Army. In Europe there are many institutes also invested in developing a vaccine. But all these vaccines have failed in trials done throughout the world either in the U.S. or the endemic area. The first phase has to be done with healthy volunteers in the U.S. Provided it is safe, it is then tested in an area where malaria is endemic. Almost all these vaccines have shown to be ineffective.

So, there is a renewed effort to find new antigens, new candidates for vaccine development. The malaria parasites express almost 6,000 proteins. It is a large genome, a very complex microorganism. But it has the ability to use these proteins for a variety of purposes. It multiplies tremendously and efficiently, and it has the ability to evade our natural immune responses.

It has been my concern for years that we invested a lot of time and money working with 10 to 12 antigens and that these vaccines were doomed to fail.  The only one that looks promising is the one researchers at the Walter Reed Army Institute (WRAIR), where I work, are developing with support from Glaxo-Smith Kline. This vaccine is in late stages of testing in Africa. It has the ability to protect about 50 percent of the vaccinees, but only for about a year. So we have a vaccine that is in the last stages of development that has cost millions and millions of dollars in investment – not only by Glaxo Smith Kline but also by the Gates Foundation. But this vaccine, RTS,S, is not 100 percent effective and it doesn’t last a long time. So there is interest in finding additional antigens, additional candidates for vaccines.

We gave a presentation to USAID about two malaria proteins we discovered that are very promising. NMRC and the Malaria Vaccine Institute (MVI), which is a nonprofit organization funded mainly by the Bill and Melinda Gates Foundation (BMGF), funds the work. USAID and MVI had wanted to hear about the results we have produced in the last few years.  So we, WRAIR, and NIH working on a similar project gave a presentation.  The meeting was open to federal workers from CDC (Centers for Disease Control and Prevention), NIH, FDA (Food and Drug Administration), Army, and Navy; there were approximately 50 scientists. USAID thought we had made huge progress, and we are continuing discussions with them.

CAMRIS: So there is regular coordination between the Army, European organizations, the Gates Foundation, MVI, USAID, and other donors?

João: Yes, we work with funding from MVI and DoD. Together with another collaborating forum at NIH, we have formed this consortium. So there is a lot of communication and exchange of ideas with various groups. We work with the private sector and universities as well as government scientists. It takes time, hard work, and money to develop a vaccine. 

CAMRIS: On a regular day what do you do?

João: My daily dream activity is in the lab.  Wearing the lab coat and gloves, doing experiments, that is what I love to do and what I used to do. Nowadays, I don’t have that time. But every day I meet with the technicians in the lab and discuss the experiments that they are doing, the results of the experiments, and why it didn’t work or did work.  

I spend a lot of time reading papers, looking for new ideas. I exchange emails with others working in the field. I have a range of collaborators. Sometimes I get accused of having too many collaborators. Today I have another meeting with another collaborator, a private company. So, I spend most of my days working on the computer and thinking about ideas and projects. 

CAMRIS: What is your background, your previous work history? How did you get into this field of work initially? 

João: I was a medical student in Brazil, and I got a little bit frustrated with the medical profession. It was too focused on making money. The way you see a patient for just a few minutes and they write a check, I didn’t like that. I wanted to be dedicated more to the health of people.

I made a decision while I was in medical school to work on science and work on tropical diseases. I used to walk around the hospital and ask doctors and scientists lots of questions, as I tried to figure out what I should delve into. One day in 1980, I was called to see the director of the hospital and he showed me the journal Science. It had a micrograph of a malaria parasite invading a red blood cell. That was a breakthrough because no one knew then how malaria invaded the cell. Malaria was a disease of big importance in the world of health, but not in Brazil. The morbidity was high, though, in other countries. So, I decided I wanted to work on that.  

After I graduated, I taught in the medical school, and then went to London where I received my MSc in medical parasitology at London School of Hygiene and Tropical Medicine and PhD in molecular parasitology at the National Institute for Medical Research. Next, I went to work in a biotech company in Palo Alto, California. I then moved to the Navy where I have been since 1994. There is a large department working on malaria. Some are military and other civilian personnel, either GS [government] or contractors, like CAMRIS. I also work with the private sector and universities, like New York University (NYU).  I am very interested in the technology that the private sector has been developing. Not only for vaccines but also for different approaches for diseases. We take advantage of that. We are now working with a university in Oregon. They have developed technology for vaccine development to HIV/AIDS and Tuberculosis, and we will use their technology for our work. It looks very promising.   

CAMRIS:   Will we eradicate malaria in our lifetime?

João: The widespread use of insecticides and anti-malaria drugs has not worked, mainly because the mosquitos and parasites developed ways of resisting the insecticides and the drugs. These days insecticides are barely used and are actually banned in most countries because of the damage of their use to the environment. A lot of drugs we used 20 years ago are pretty much useless as far as treatment goes today.  But there have been a few drugs developed in the last few years that look very promising.  Ultimately, we think that it will be a combination of these different factors and a vaccine.

There are many different preventive methods like bed net distribution and use. Bed net use is difficult to enforce – most people don’t adhere when it is hot; people stop using them. But bed nets are very effective and have dramatically reduced the number of malaria infections, especially for children.  

CAMRIS: Have you lived in an area where malaria is endemic and used a bed net?

João: I grew up using bed nets when I was a kid in Brazil – not because of malaria or any disease but to prevent mosquito bites. In some areas of Brazil, there are lots of mosquitos, especially in the wet season. My parents were very strict and I had to use bed nets.  But I know it is a nuisance – especially when you get a mosquito inside of your bed net!

If you look at what the Gates Foundation has been proposing, it is not one measure but rather a multi-approach to eradicate or control malaria. The word eradication has been thrown out a lot lately, but it is something very difficult to achieve. So we are looking to “control” or “manage” malaria incidence to very low levels using these interventions, such as bed nets, preventive drugs, insecticides, and an effective vaccine.

CAMRIS: What do you do when you aren’t working?

João:  I am very dedicated to my work. It is a problem because it is very hard to switch off. My wife calls it Sunday night syndrome.  Every Sunday night I think about work and it takes me hours to get to sleep. It is because Monday is a big day, it’s a new week.  I think a lot about what I will be doing. It is a dedication.

But I like to do other things, too. I have a wife and daughter and I like to spend time with them. We like to go out, like to stroll around, especially in museums. I do a lot of jogging and biking. Jogging is my main physical activity. I used to jog every day until I had a problem with my meniscus and had surgery. Now I can only jog two and three times a week. But I also love biking – especially long rides, like 300 miles.  

CAMRIS: So are you hopeful that in your lifetime there will be a vaccine?

João: Yes! Yes, I am very optimistic. How effective this will be is unclear. That is why we are still looking for alternatives.  

We are in discussion with USAID, but it looks very promising.

We cannot just put all our eggs in one basket. That would be unwise.  We know that these vaccines sometimes fail.

But still, I’m very hopeful. There is a new generation of scientists. Technology has improved so much. For me, I’ve been in this work for about 35 years and this is the biggest change. Technology has improved dramatically. We can take a microorganism that has 50,000 proteins and we can dissect all this stuff in a few weeks using high throughput techniques, which allows us to analyze thousands of genes or proteins simultaneously.

CAMRIS: You seem very passionate about your work and that you have found a job that makes you happy.  

João: I am!