WASHINGTON -- A small clinical trial of a malaria vaccine candidate recently showed 100-percent protection against the disease. This could mean, with enough funding, that a first-generation vaccine may be ready in 4 to 5 years for deployed war fighters and people in endemic areas, a Navy researcher said Aug. 15.
Dr. Judith Epstein, clinical director of malaria vaccine development at the Naval Medical Research Center and NMRC's lead investigator on the study, told American Forces Press Service that the 40-person phase 1 clinical trial is historic in its success and has come after decades of work on a vaccine to prevent the ancient, deadly disease.
"My effort as a Navy captain is to develop a vaccine that can be used for warfighters," Epstein said.
Malaria is a major challenge in many parts of the world. This includes most of sub-Saharan Africa and South Asia, Southeast Asia, Oceania, Central Asia, the Middle East, Central and South America and the Caribbean.
"As a bonus, we are also hoping that vaccine could be used in endemic countries," Epstein added. "... We need something for the military that's highly effective, meaning you take the vaccine, you don't get malaria. That's the same thing they need in countries where they have malaria."
For the trial, NMRC collaborated with federal scientists from the Vaccine Research Center at the National Institutes of Health, Army and civilian scientists from the Walter Reed Army Institute of Research, and scientists from vaccine developer and manufacturer Sanaria Inc., all in Maryland.
In the clinical trial, the vaccine candidate was given at different dosages by intravenous injection to 40 volunteers from October 2011 to October 2012. The trial ended in June 2013.
Three weeks after the final dose of vaccine, Epstein said, "we did what's called a controlled human malaria infection. We challenged them with mosquitoes that carry malaria. We put five infected mosquitoes in a cup [upside down] on the person's arm. The mosquitoes bit them and we carefully followed the patients over the next week. In fact, we admitted them [to the medical center] so we could watch them and we tested to see if they developed malaria or not."
She added, "In the group that got the highest dose of vaccine and that got five doses, all six of the six were protected. In the group that got the highest dose but that got only four doses -- so they got the highest amount per vaccination -- six of nine were protected."
But what's in the latest malaria vaccine is nearly as historic as its success: Whole parasites -- the very Plasmodium falciparum parasites that infect 30 or 40 species of female Anopheles mosquitoes whose bites transfer the parasites to people and give them malaria.
But the parasites that make up the vaccine are irradiated so they are weakened and don't cause disease, Epstein said, the same way viruses that make up vaccines for smallpox, polio and measles are weakened to produce immunity rather than disease.
Also, she added, the parasites come from mosquitoes that are grown aseptically in a laboratory built for that purpose that meets strict Food and Drug Administration requirements.
Most malaria vaccines in clinical development today are made from genetically engineered proteins that represent small parts of the malaria parasite. But Epstein said that studies in the early 1970s by Navy and University of Maryland researchers showed the benefit of full-organism immunity using irradiated mosquitoes.
In those studies, Epstein said, the researchers irradiated mosquitoes, and the parasites inside them, and then had lots of the mosquitoes bite volunteers. At the time, this was the only way to inject irradiated parasites into the volunteers.
"They knew that if you gave people enough of the mosquito [bites] you could protect them [from malaria], but in everyone's mind they said, 'How can we have a vaccine that's made up of mosquitoes? That's not possible,'" she said.
Researchers thought they'd use the idea as a model and try to understand why it worked, she added.
"Then about 2004 or 2005," Epstein said, "our collaborators at Sanaria along with Navy investigators said, 'We think we can do what everyone thinks is crazy and impossible, and that is grow up these mosquitoes in what we call a [good manufacturing practice] facility so it goes through all the FDA requirements. We can dissect out those parasites after they've been irradiated and put them in a vial ... and give them safely to people.'"
The vaccine is a clear liquid, about a fifth of a milliliter, given into a vein with a very small syringe. People barely feel the shot, Epstein said.
The next steps for the vaccine, which the developer calls the Sanaria PfSPZ vaccine, will be a series of trials in the United States and around the world.
In September, Sanaria will do a field trial in Tanzania and within the next year NIH will do a trial with Navy involvement that will test the durability of the vaccine over six months.
The next Navy trial, Epstein said, "will be with the Naval Medical Research Center and the Walter Reed Institute of Research. We're hoping to begin in the first quarter of next year if we have adequate funding."
That trial will determine how long the vaccine will last in adult volunteers. The researchers will also test a fewer number of doses and, working with Sanaria, will do controlled tests with different strains of malaria.
"When people get infected with malaria they're getting infected sometimes with several different strains at once," Epstein said. "Malaria is a very formidable enemy. I think that's why we're so excited about this [vaccine] working is because there are so many challenges in trying to deal with malaria."
In controlled tests, she explained, one group will test one strain and another group will test another strain. When people in the wild are bitten by mosquitoes, they get a few different strains at once. All field trials in other countries will be testing multiple strains of malaria.
Another NIH trial, at the end of this year or next year, will be held in Mali or Uganda, Epstein said, adding, "There's a lot of activity going on."
Ultimately, she hopes to license the vaccine through the FDA within 4 to 5 years for a first-generation vaccine that is ready for broader testing. Down the road, a second- or third-generation vaccine may reflect findings from worldwide use.
Epstein says millions of dollars will be needed to complete the trials, and that so far major funding has come from the Defense Department, the National Institutes of Health, and the Bill and Melinda Gates Foundation.
Some funding also will come from the consortium of federal agencies, academia and industry that will conduct trials with partners.
"This trial is the beginning," Epstein said. "We have proved in a small group of people that this can be done. I think someone might say, 'Well, okay, six people. Why is that so important?' It's so important because nothing like this has ever been done before. This is proof of concept."