Malaria Derived Glycosylphosphatidylinositol Anchor
Enhances Anti-Pfs25 Functional Antibodies That Block Malaria Transmission
Version 2 2018-01-17, 00:29
Version 1 2018-01-13, 18:30
Posted on 2018-01-17 - 00:29
Malaria,
one of the most common vector borne human diseases, is a major world
health issue. In 2015 alone, more than 200 million people were infected
with malaria, out of which, 429 000 died. Even though artemisinin-based
combination therapies (ACT) are highly effective at treating malaria
infections, novel efforts toward development of vaccines to prevent
transmission are still needed. Pfs25, a postfertilization stage parasite
surface antigen, is a leading transmission-blocking vaccine (TBV)
candidate. It is postulated that Pfs25 anchors to the cell membrane
using a glycosylphosphatidylinositol (GPI) linker, which itself possesses
pro-inflammatory properties. In this study, Escherichia coli derived extract (XtractCF+TM) was used in cell free protein
synthesis [CFPS] to successfully express >200 mg/L of recombinant
Pfs25 with a C-terminal non-natural amino acid (nnAA), namely, p-azidomethyl phenylalanine (pAMF), which possesses a reactive
azide group. Thereafter, a unique conjugate vaccine (CV), namely,
Pfs25-GPI was generated with dibenzocyclooctyne (DBCO) derivatized
glycan core of malaria GPI using a simple but highly efficient copper
free click chemistry reaction. In mice immunized with Pfs25 or Pfs25-GPI,
the Pfs25-GPI group showed significantly higher titers compared to
the Pfs25 group. Moreover, only purified IgGs from Pfs25-GPI group
were able to significantly block transmission of parasites to mosquitoes,
as judged by a standard membrane feeding assay [SMFA]. To our knowledge,
this is the first report of the generation of a CV using Pfs25 and
malaria specific GPI where the GPI is shown to enhance the ability
of Pfs25 to elicit transmission blocking antibodies.
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Kapoor, Neeraj; Vanjak, Ivana; Rozzelle, James; Berges, Aym; Chan, Wei; Yin, Gang; et al. (2018). Malaria Derived Glycosylphosphatidylinositol Anchor
Enhances Anti-Pfs25 Functional Antibodies That Block Malaria Transmission. ACS Publications. Collection. https://doi.org/10.1021/acs.biochem.7b01099
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AUTHORS (14)
NK
Neeraj Kapoor
IV
Ivana Vanjak
JR
James Rozzelle
AB
Aym Berges
WC
Wei Chan
GY
Gang Yin
CT
Cuong Tran
AS
Aaron K. Sato
AS
Alexander R. Steiner
TP
Thao P. Pham
AB
Ashley J. Birkett
CA
Carole A. Long
JF
Jeff Fairman
KM
Kazutoyo Miura
KEYWORDS
derivatized glycan corePfs 25-GPImalariaBlock Malaria Transmission MalariaTBVPfs 25Pfs 25-GPI groupartemisinin-based combination therapiesreactive azide groupDBCOclick chemistry reactionSMFAMalaria Derived Glycosylphosphatidylinositol Anchor Enhances Anti-Pfs 25 Functional Antibodiesworld health issueCVCFPSpostfertilization stage parasite surface antigenPfs 25 groupPfs 25 anchorsTM