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Elucidating functional epitopes within the N-terminal region of malaria transmission blocking vaccine antigen Pfs230

January 18, 2022 - 20:44 -- Open Access
Miura K, Takashima E, Tsuboi T, et al.
NPJ Vaccines. 2022 Jan 13;7(1):4

Pfs230 is a leading malaria transmission blocking vaccine (TBV) candidate. Comprising 3135 amino acids (aa), the large size of Pfs230 necessitates the use of sub-fragments as vaccine immunogens.

Pfs230 yields higher malaria transmission-blocking vaccine activity than Pfs25 in humans but not mice

February 10, 2021 - 10:03 -- Open Access
Healy SA, Anderson CF, Duffy PE, et al.
J Clin Invest. 2021 Feb 9:146221

Vaccines that block human-to-mosquito Plasmodium transmission are needed for malaria eradication and clinical trials have targeted zygote antigen Pfs25 for decades. We reported that a Pfs25 protein-protein conjugate vaccine formulated in alum adjuvant induced significant serum functional activity in both US and Malian adults. However, antibody titers declined rapidly, and transmission-reducing activity required four vaccine doses. Functional immunogenicity and durability must be improved before advancing TBV further in clinical development. We hypothesized that the pre-fertilization protein Pfs230 alone or in combination with Pfs25 would improve functional activity.

Particle-based, Pfs230 and Pfs25 immunization is effective, but not improved by duplexing at fixed total antigen dose

September 1, 2020 - 09:54 -- Open Access
Wei-Chiao Huang, Bingbing Deng, Moustafa T. Mabrouk, Amal Seffouh, Joaquin Ortega, Carole Long, Kazutoyo Miura, Yimin Wu and Jonathan F. Lovell
Malaria Journal 2020 19:309, 28 August 2020

The Plasmodium falciparum sexual-stage surface proteins Pfs25 and Pfs230 are antigen candidates for a malaria transmission-blocking vaccine (TBV), and have been widely investigated as such. It is not clear whether simultaneously presenting these two antigens in a particulate vaccine would enhance the transmission reducing activity (TRA) of induced antibodies. To assess this, immunization was carried out with liposomes containing synthetic lipid adjuvant monophosphoryl lipid A (MPLA), and cobalt-porphyrin-phospholipid (CoPoP), which rapidly converts recombinant, his-tagged antigens into particles.

Structure and function of a malaria transmission blocking vaccine targeting Pfs230 and Pfs230-Pfs48/45 proteins

July 27, 2020 - 15:01 -- Open Access
Singh K, Burkhardt M, Narum DL, et al.
Commun Biol. 2020 Jul 24;3(1):395

Proteins Pfs230 and Pfs48/45 are Plasmodium falciparum transmission-blocking (TB) vaccine candidates that form a membrane-bound protein complex on gametes. The biological role of Pfs230 or the Pfs230-Pfs48/45 complex remains poorly understood. Here, we present the crystal structure of recombinant Pfs230 domain 1 (Pfs230D1M), a 6-cysteine domain, in complex with the Fab fragment of a TB monoclonal antibody (mAb) 4F12. We observed the arrangement of Pfs230 on the surface of macrogametes differed from that on microgametes, and that Pfs230, with no known membrane anchor, may exist on the membrane surface in the absence of Pfs48/45.

NOT Open Access | Comparison of carrier proteins to conjugate malaria transmission blocking vaccine antigens, Pfs25 and Pfs230

June 30, 2020 - 14:53 -- NOT Open Access
Scaria PV, Chen BB, Duffy PE, et al.
Vaccine. 2020 Jun 26:S0264-410X (20)30790-8

Malaria transmission blocking vaccines (TBV) target the sexual stage of the parasite and have been pursued as a stand-alone vaccine or for combination with pre-erythrocytic or blood stage vaccines. Our efforts to develop TBV focus primarily on two antigens, Pfs25 and Pfs230. Chemical conjugation of these poorly immunogenic antigens to carrier proteins enhances their immunogenicity, and conjugates of these antigens to Exoprotein A (EPA) are currently under evaluation in clinical trials.

The Pfs230 N-terminal fragment, Pfs230D1+: expression and characterization of a potential malaria transmission-blocking vaccine candidate

November 11, 2019 - 16:13 -- Open Access
Shwu-Maan Lee, Yimin Wu, John M. Hickey, Kazutoyo Miura, Neal Whitaker, Sangeeta B. Joshi, David B. Volkin, C. Richter King and Jordan Plieskatt
Malaria Journal 2019 18:356, 8 November 2019

Control and elimination of malaria can be accelerated by transmission-blocking interventions such as vaccines. A surface antigen of Plasmodium falciparum gametocytes, Pfs230, is a leading vaccine target antigen, and has recently progressed to experimental clinical trials. To support vaccine product development, an N-terminal Pfs230 antigen was designed to increase yield, as well as to improve antigen quality, integrity, and homogeneity.

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