Investigational malaria vaccine gives strong, lasting protection

Investigational malaria vaccine gives strong, lasting protection

Two U.S. Phase 1
clinical trials of a novel candidate malaria vaccine have found that the
regimen conferred unprecedentedly high levels of durable protection when
volunteers were later exposed to disease-causing malaria parasites. The vaccine
combines live parasites with either of two widely used antimalarial drugs–an
approach termed chemoprophylaxis vaccination. A Phase 2 clinical trial of the
vaccine is now underway in Mali, a malaria-endemic country. If the approach
proves successful there, chemoprophylaxis vaccination, or CVac, potentially
could help reverse the stalled decline of global malaria. Currently, there is
no vaccine in widespread use for the mosquito-transmitted disease.

The trials were
conducted at the National Institutes of Health (NIH) Clinical Center in
Bethesda, Maryland. They were led by Patrick E. Duffy, M.D., of the NIH
National Institute of Allergy and Infectious Diseases (NIAID), and Stephen L.
Hoffman, M.D., CEO of Sanaria Inc., Rockville, Maryland.

The Sanaria
vaccine, called PfSPZ, is composed of sporozoites, the form of the malaria
parasite transmitted to people by mosquito bites. Sporozoites travel through
blood to the liver to initiate infection. In the CVac trials, healthy adult
volunteers received PfSPZ along with either pyrimethamine, a drug that kills
liver-stage parasites, or chloroquine, which kills blood-stage parasites. Three
months later, under carefully controlled conditions, the volunteers were
exposed to either an African malaria parasite strain that was the same as that
in the vaccine (homologous challenge) or a variant South American parasite
(heterologous challenge) that was more genetically distant from the vaccine
strain than hundreds of African parasites. Exposure in both cases was via
inoculation into venous blood, which infects all unvaccinated individuals.

At the lowest PfSPZ
dosage, the CVac approach conferred modest protection: only two of nine
volunteers (22.2%) who received the pyrimethamine combination were protected
from homologous challenge. In contrast, seven out of eight volunteers (87.5%)
who received the highest PfSPZ dosage combined with pyrimethamine were
protected from homologous challenge, and seven out of nine volunteers (77.8%)
were protected from heterologous challenge. In the case of the chloroquine
combination, all six volunteers (100%) who received the higher PfSPZ dosage
were completely protected from heterologous challenge. The high levels of
cross-strain protection lasted at least three months (the time elapsed between
vaccination and challenge) for both higher-dose regimens. One hundred percent
protection for three months against heterologous variant parasites is
unprecedented for any malaria vaccine in development, the authors note. These
data suggest that CVac could be a promising approach for vaccination of
travelers to and people living in malaria-endemic areas.

Mwakingwe-Omari et al. Two chemoattenuated
PfSPZ malaria vaccines induce sterile hepatic immunity 
Nature DOI:
10.1038/s41586-021-03684-z (2021).

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