Researchers have modified an
experimental malaria vaccine and showed that it completely protected four of
eight monkeys that received it against challenge with the virulent Plasmodium
falciparum malaria parasite. In three of the remaining four monkeys, the
vaccine delayed when parasites first appeared in the blood by more than 25
days.
Malaria symptoms occur when parasites
replicate inside red blood cells and cause them to burst. To enter blood cells,
the parasite first secretes its own receptor protein, RON2, onto the cell's
surface. Another parasite surface protein, AMA1, then binds to a specific
portion of RON2, called RON2L, and the resulting complex initiates attachment
to the outer membrane of the red blood cell.
Several experimental malaria vaccines
previously tested in people were designed to elicit antibodies against AMA1 and
thus prevent parasites from entering blood cells. Although AMA1 vaccines did
generate high levels of antibodies in humans, they have shown limited efficacy
in field trials in malaria-endemic settings.
To improve vaccine efficacy, the NIAID
scientists modified an AMA1 vaccine to include RON2L so that it more closely
mimics the protein complex used by the parasite. Monkeys were vaccinated with
either AMA1 alone or with the AMA1-RON2L complex vaccine. Although the overall
levels of antibodies generated did not differ between the two groups, animals
vaccinated with the complex vaccine produced much more neutralizing antibody, indicating
a better quality antibody response with AMA1-RON2L vaccination. Moreover,
antibodies taken from AMA1-RON2L-vaccinated monkeys neutralized parasite
strains that differed from those used to create the vaccine. This suggests, the
authors note, that an AMA1-RON2L complex vaccine could protect against multiple
parasite strains. Taken together, the data from this animal study justify
progression of this next-generation AMA1 vaccine toward possible human trials,
they conclude.
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Posted by Dr. Tim Sandle