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Malaria: Next-generation vaccine

shows efficacy, safety in humans
Written by Honor Whiteman
Published: Sunday 8 January 2017

A next-generation vaccine that uses a weakened form of a malaria parasite has demonstrated efficacy
and safety in a small number of humans.
Researchers found that GAP3KO stimulated an effective immune response against the deadly malaria parasite Plasmodium
falciparum.

In a study recently published in Science Translational Medicine, researchers reveal that

a vaccine called GAP3KO stimulated an effective immune response against the
deadly malaria parasite Plasmodium falciparum, without causing any serious side
effects.
Malaria is a potentially fatal bloodborne disease caused by Plasmodium parasites,
which are most commonly spread though the bites of female Anopheles mosquitoes.
P. falciparum is the most widespread malaria parasite, and it is also one of the most
deadly; if P. falciparum malaria is not treated within 24 hours, it can cause serious
illness or death.
According to the World Health Organization (WHO), there were approximately 212
million new cases of malaria worldwide, and around 429,000 deaths from the disease,
in 2015. More than 90 percent of malaria cases and deaths occur in sub-Saharan
Africa, with the highest burden among children under the age of 5.

At present, there is no licensed vaccine for malaria. Prevention strategies for malaria
include insecticides, bed nets, and antimalarial drugs, while the primary treatment for
the disease is artemisinin-based combination therapy.

Malaria vaccine development: The road so far

While current prevention and treatment methods can be effective against malaria,
researchers and health organizations across the globe are in agreement that an
effective vaccine is needed in order to eliminate the disease completely.

Until now, a vaccine named RTS,S had proven the most promising candidate.
The results of a Phase III trial published in April 2015 showed that RTS,S -
manufactured by pharmaceutical giant GlaxoSmithKline - reduced the number of clinical
malaria cases in young children and infants by 26-36 percent over a 3-year period.
RTS,S uses genetically engineered proteins from P. falciparum to generate an immune
response, which can stop the parasite from infecting the liver and causing malaria
symptoms.
Based on the success of RTS,S in clinical trials, the vaccine will be rolled out in three
countries in sub-Saharan Africa in 2018, as part of the WHO's malaria vaccine pilot
program.
However, the new study suggests a different approach that might lead to the
development of a vaccine that is more effective than RTS,S.

GAP3KO triggered antibody response to

malaria parasite in humans
The new research describes a vaccine called GAP3KO. Instead of utilizing components
of the P. falciparum parasite like RTS,S does, GAP3KO has been created using a
weakened version of the entire parasite.
Researchers weakened P. falciparum by removing three genes that the parasite needs
in order to enter the bloodstream, infect humans, and cause illness.
For their study, the scientists gave mice a rodent version of GAP3KO. They found that it
protected against malaria infection when the mice were later exposed to an unmodified
version of P. falciparum.

Next, the researchers enrolled 10 human volunteers. Each participant was bitten
approximately 150-200 times by mosquitoes that had been infected with GAP3KO.

The researchers found that GAP3KO caused each individual to develop

antibodies against sporozoites - the immature forms of P. falciparum parasites
that cause human infection - and none of the subjects developed malaria or
experienced any serious side effects.

"We had already good indicators in preclinical studies that this new 'triple knock-out'
GAP (GAP3KO), which has three genes removed, is completely attenuated," says study
co-author Sebastian Mikolajczak, Ph.D., principal scientist at the Center for Infectious
Disease Research (CIDR) in Seattle, WA.

"The clinical study now shows that the GAP3KO vaccine is completely attenuated
in humans and also shows that even after only a single administration, it elicits a
robust immune response against the malaria parasite. Together these findings
are critical milestones for malaria vaccine development."

Sebastian Mikolajczak, Ph.D.

Findings represent a 'major advance in malaria
vaccine development'
The team's results have been met with much optimism; Dr. Robert Sedar, chief of
cellular immunology at the Vaccine Research Center of the National Institutes of Health
(NIH) - who was not involved in the research - hails the findings as a "major advance in
malaria vaccine development."

"Future studies demonstrating protective efficacy will be the next critical milestone for
continued development of this promising vaccine approach," he adds.

Study co-author Dr. James Kublin, a scientist at the Fred Hutchinson Cancer Research
Center in Seattle, WA, and medical director of the Seattle Malaria Clinical Trials Center,
believes that the team's human malaria challenge model - whereby malaria vaccine
candidates are tested in healthy adults - puts them in a good position for future
research.

"We are very fortunate to have the human malaria challenge model to take the critical
next step evaluating the efficacy of GAP3KO in preventing malaria in people," he says.

"The Hutch is looking forward to bringing its expertise in clinical trial design and
management to the next stage of tests for this vaccine. The collaborations we have with
CIDR and other nearby institutions is what makes Seattle a world leader in the malaria
vaccine development and the human challenge model."

Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects, Sebastian
Mikolajczak et al., Science Translational Medicine, doi: 10.1126/scitranslmed.aad9099, published online 4 January

2017, abstract.

The Feary Group news release, accessed 6 January 2017 via EurekAlert.

Additional sources:

Malaria Vaccine Initiative, Malaria vaccine candidate has demonstrated efficacy over 3-4 years of follow-up, accessed

6 January 2017.

WHO, Fact sheet: World malaria report 2016, accessed 6 January 2017.

WHO, Malaria: Key facts, accessed 6 January 2017.

WHO, Questions and answers on RTS,S/ASO1 malaria vaccine, accessed 6 January 2017.
Please use one of the following formats to cite this article in your essay, paper or report:

MLA

Whiteman, Honor. "Malaria: Next-generation vaccine shows efficacy, safety in humans." Medical News Today.

MediLexicon, Intl., 8 Jan. 2017. Web.

6 Apr. 2017. <http://www.medicalnewstoday.com/articles/315072.php>

APA

Whiteman, H. (2017, January 8). "Malaria: Next-generation vaccine shows efficacy, safety in humans." Medical News
Today. Retrieved from

http://www.medicalnewstoday.com/articles/315072.php.

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