my name is felicia watson i am a phd student in the pathobiology program in the department
of global health and i am doing my dissertation research in sean murphy's lab in the department
of laboratory medicine and pathology today i'm going to tell you about my research on improving
a two-step malaria vaccine malaria is a disease that causes an estimated 229 million infections in
400 000 deaths each year and most of these deaths occur in pregnant people or children under five
over half of the world lives in areas at risk of malaria so better vaccines are urgently needed to
save lives and reduce infections however due to the complexity of the malaria parasite vaccine
development has been extremely difficult malaria is caused by a parasite that is spread to humans
through the bite of a mosquito mosquitoes transmit parasites called sporozoites into the skin these
sporozoites go on to infect the liver for about a week before they invade into the bloodstream
this blood stage infection is the stage that makes you sick and can also be spread back to mosquitoes
so if we block this blood stage by killing off the parasites in the liver
we prevent malaria and we prevent the further spread of the parasite to new mosquitoes there's
an existing vaccine strategy called pfspz that does just this and blocks the blood stage this
vaccine is a whole sporozoite parasite that has been weakened so that does not cause disease the
vaccine is very effective in preventing malaria but it requires repeated booster vaccination
and so our lab improved and simplified this vaccine into two steps step one primes the immune
system with parasite dna and step two uses the same sporozoite vaccine from the standard pfspz
and although our vaccine is effective it still requires further optimization one limitation is
that the vaccine must be delivered directly into the bloodstream in a method called intravenous or
iv delivery iv delivery requires specialized training and is more difficult than standard
vaccination most vaccines included including the covid 19 vaccines are delivered intramuscularly
into the upper arm intramuscular injections deposit vaccine under the skin into the muscle
attempts to deliver sporozoite vaccines without iv delivery have failed and this is likely due to
less sporozoites making it into the bloodstream which is key for sporozoite vaccination however
mosquitoes successfully inject sporozoites into people's arms so we hypothesize that if
we mimic the mosquito and inject the sporozoites into the skin that this could be an effective
vaccination route sporozoites in the skin move around until they find the bloodstream
skin or intradermal vaccination is much simpler and easier for nurses
in the clinic and it would greatly improve overall sporozoite vaccine administration
thus improving intradermal vaccine delivery for malaria is the focus of my dissertation research
mosquitoes are really tiny and so they inject very small volumes of sporozoites into the skin
standard vaccines use much larger volumes which could be detrimental for the sporozoites so we
hypothesized that if we reduced the volume of the vaccine we could improve the overall efficacy
however we found that the small volume intradermal delivery was still not as
effective as iv delivery so to further improve intradermal delivery we added an adjuvant drug
adjuvants are substances that are added to vaccines to improve overall immune responses
we hypothesize that an adjuvant would help awaken the immune system and improve intradermal delivery
here i combined our sporozoite vaccine with an adjuvant called 70w85 which was designed to
improve malaria vaccination we found that if you add the adjuvant we were able to improve overall
intradermal delivery so if we put everything together we found that the combination of the
low volumes for the weight delivery and 70 w85 adjuvant was highly effective and could
be delivered intradermally we show for the first time that sporozoite vaccines can be delivered
intradermally and achieve equivalent levels of protection to iv delivery it seems like the
combination of low volume and drug adjuvant is critical for effective intradermal vaccination
so in summary we demonstrate that sporozoite vaccines can be delivered intradermally
if you combine 70 w85 and small volume intradermal delivery this intradermal delivery is mimicking
the mosquito and delivering sporozoites into the skin where they can migrate on their own into
the bloodstream this new vaccine administration improves the accessibility of the malaria vaccine
as previously it was required to be administered iv iv delivery requires specialized training and
is much more difficult and time consuming for nurses and as malaria impacts millions of people
every year improving vaccine accessibility is a major public health focus and so here
we demonstrate that we can further improve this existing vaccine to make it easier to administer