By Cheryl Pellerin
American Forces Press Service
WASHINGTON, Aug. 15, 2013 – 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 warfighters and people
in endemic areas, a Navy researcher said.
U.S.
Marine Corps Cpl. Timothy Dobson takes doxycycline, used to prevent
malaria, once a day in accordance with a weekly dosage of mefloquine,
also an antimalarial, April 23, 2011, in Toubakouta, Senegal. U.S.
Marine Corps photo by Lance Cpl. Timothy L. Solano (Click photo for screen-resolution image);high-resolution image available. |
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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.”