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Infection and Immunity, October 2000, p. 5530-5538, Vol. 68, No. 10
0019-9567/00/$04.00+0
A Region of Plasmodium falciparum
Antigen Pfs25 That Is the Target of Highly Potent
Transmission-Blocking Antibodies
Anthony W.
Stowers,*
David B.
Keister,
Olga
Muratova, and
David C.
Kaslow
Malaria Vaccine Development Unit, Laboratory
of Parasitic Diseases, National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, Maryland 20892-0425
Received 8 March 2000/Returned for modification 12 May
2000/Accepted 4 July 2000
Each of the four epidermal growth factor (EGF)-like domains of the
Plasmodium falciparum sexual-stage antigen Pfs25 has been individually expressed as a yeast-secreted recombinant protein (yEGF1
through yEGF4). All four are recognized by the immune sera of animals
and humans vaccinated with TBV25H (the corresponding yeast-secreted
full-length recombinant form of Pfs25), with antibody titers to yEGF1
and yEGF2 weakly correlating with the ability of the sera to block the
transmission of parasites to the mosquito host. All four proteins are
poorly immunogenic in mice vaccinated with aluminum hydroxide-absorbed
formulations. However, all four successfully primed the mice to mount
an effective secondary antibody response after a single boost with
TBV25H. Sera from mice vaccinated with yEGF2-TBV25H completely block
the development of oocysts in mosquito midguts in membrane-feeding
assays. Further, of the four proteins, only the depletion of antibodies
to yEGF2 from the sera of rabbits vaccinated with TBV25H consistently
abolished the ability of those sera to block oocyst development. Thus,
antibodies to the second EGF-like domain of Pfs25 appear to mediate a
very potent blocking activity, even at low titers. Vaccination
strategies that target antibody response towards this domain may
improve the efficacy of future transmission-blocking vaccines.
*
Corresponding author. Mailing address: Malaria Vaccine
Development Unit, LPD/NIAID/NIH, Twinbrook II Room 103, 12441 Parklawn Dr., Rockville, MD 20852. Phone: (301) 435-2968. Fax: (301) 435-6725. E-mail: astowers{at}niaid.nih.gov.

Present address: Viral and Vaccine Research, Merck Research Labs,
West Point, PA
19486.
Infection and Immunity, October 2000, p. 5530-5538, Vol. 68, No. 10
0019-9567/00/$04.00+0
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