NIH: An investigational malaria vaccine given intravenously was well-tolerated and protected a significant proportion of healthy adults against infection with Plasmodium falciparum malaria — the deadliest form of the disease — for the duration of the malaria season, according to new findings published in the February 15th issue of the journal Lancet Infectious Diseases. The study participants live in Mali, Africa, where they are naturally exposed to the parasite.
The investigational vaccine, known as the PfSPZ Vaccine, contains
live but weakened sporozoites, the form of the parasite that infects
humans, and was developed by scientists at Sanaria Inc., of Rockville,
Maryland. The study was conducted by researchers from the National
Institute of Allergy and Infectious Diseases (NIAID), part of the
National Institutes of Health, and the University of Science,
Techniques, and Technologies of Bamako (USTTB), Mali, one of NIAID’s
International Centers of Excellence in Malaria Research.
In 2015, 212 million cases of malaria occurred worldwide, and 429,000
people with malaria died, largely African children under five years
old, according to the World Health Organization. Although only 1,500 to
2,000 cases of malaria are diagnosed in the United States each year, the
disease is a concern for international travelers, aid workers and
military personnel worldwide.
“Considerable progress has been made in the global fight against
malaria within the past decade, yet far too many people — particularly
young African children — continue to become infected and die from the
disease,” said NIAID Director Anthony S. Fauci, M.D. “A safe, effective
vaccine to protect against this mosquito-borne illness would greatly
help efforts to bring the disease under control.”
Humans acquire malaria through the bite of infected mosquitoes, which
inject parasites in the sporozoite stage of their life cycle into the
bloodstream. The parasites travel to the liver, multiply, and then
spread throughout the bloodstream causing malaria symptoms, including
chills, fever, headache, nausea, sweating and fatigue.
PfSPZ Vaccine uses live but weakened sporozoites of the malaria
parasite species P. falciparum to generate an immune response to protect
against malaria infection. Earlier research found that the experimental
vaccine safe and protective against malaria infection for up to a year in healthy U.S. adults who had not been previously exposed to malaria.
The Mali study was launched in January 2014 to provide additional
safety data about PfSPZ Vaccine and determine if it could protect adults
living in a malaria-endemic area against naturally occurring malaria
infection. The study enrolled 109 healthy African men and non-pregnant
women ages 18 to 35 years old. It was led by co-principal investigators
Sara Healy, M.D., M.P.H., of NIAID’s Laboratory of Malaria Immunology
and Vaccinology, and Mahamadou Sissoko, M.D., M.P.H., of USTTB’s Malaria
Research and Training Center.
Participants received either five doses of the intravenous PfSPZ
Vaccine or five doses of placebo (saline) over five months of the dry
season at the study’s clinical site in the Donéguébougou village in
rural Mali. Clinical staff then actively monitored the participants
during the six-month rainy, malaria-transmission season for the presence
of malaria parasites in the blood.
The investigators report that the vaccine candidate was
well-tolerated and safe with no serious adverse events. Among the 40
participants who received five placebo doses, 93 percent (37
participants) developed P. falciparum malaria infections; by comparison,
66 percent (27 participants) of the participants who received five
doses of the PfSPZ Vaccine (41 participants) developed malaria
infection. Based on the primary study analysis, PfSPZ Vaccine
demonstrated a 48 percent protective efficacy by time-to-first positive
malaria blood smear and 29 percent efficacy by proportion of
participants with at least one positive malaria blood smear during a
full 20-week malaria transmission season. By both measures of protective
efficacy, there was statistically significant protection in the vaccine
group as compared with the placebo group.
“This level of sustained efficacy against malaria infection in a
region with an intense transmission season has not been seen in previous
malaria vaccine studies in Africa,” said Dr. Healy. “It is a very
encouraging finding that we can, hopefully, build upon.”
The vaccine-induced antibody response was considerably lower in the
Mali study, however, than in the U.S. trial even though study
participants received the same vaccine regimen.
“The poor antibody response to PfSPZ Vaccine among Malians could have
been because of the participants’ lifelong exposure to P. falciparum,”
said Patrick E. Duffy, M.D., chief of NIAID’s Laboratory of Malaria
Immunology and Vaccinology.
The investigators report that the intravenous delivery system for the
PfSPZ Vaccine did not pose a problem to administer in a rural,
malaria-endemic area — an initial concern about the experimental
vaccine’s unique design.
“Direct venous inoculation is not currently used for any licensed
vaccines to prevent an infectious disease,” said Professor Ogobara
Doumbo, M.D., Ph.D., senior scientist for the Mali malaria vaccine
program and chair of the Department of Epidemiology of Parasitic
Diseases at USTTB. “In this study, we administered 491inoculations in a
rural setting without a problem, and the dosages were delivered in a
matter of seconds. It shows that this approach is feasible from both a
logistical and public health standpoint.”
According to the researchers, a preventive malaria vaccine employed
in mass vaccination programs to eliminate P. falciparum from
geographically defined areas would need to prevent malaria infection or
transmission in at least 80 percent of recipients throughout the malaria
transmission season. Clinical trials now underway in Africa, Europe and
the United States have been designed to boost PfSPZ Vaccine’s efficacy
by increasing dosage levels and varying the timing and number of doses.
The experimental vaccine is also being examined in demographic groups
other than healthy adults, including adolescents, children and
Sanaria was the regulatory sponsor of the trial; NIAID supported the
development of the vaccine through the Small Business Innovation
Research award 5R44AI055229.
Additional information about the PfSPZ Vaccine trial in Mali is available at ClinicalTrials.gov using the identifier NCT01988636.
A follow-up study examining a three-dose PfSPZ Vaccine regimen with
higher dosage levels has just been completed by the same clinical team
in Mali, Africa. Results from that study will be available in mid-2017.
Additional information about that research is also available at ClinicalTrials.gov using the identifier NCT02627456.
NIAID conducts and supports research — at NIH, throughout the United
States, and worldwide — to study the causes of infectious and
immune-mediated diseases, and to develop better means of preventing,
diagnosing and treating these illnesses. News releases, fact sheets and
other NIAID-related materials are other NIAID-related materials are
available on the NIAID website.