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In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP).

Publication ,  Journal Article
Livingstone, MC; Bitzer, AA; Giri, A; Luo, K; Sankhala, RS; Choe, M; Zou, X; Dennison, SM; Li, Y; Washington, W; Ngauy, V; Tomaras, GD ...
Published in: Sci Rep
March 5, 2021

Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

March 5, 2021

Volume

11

Issue

1

Start / End Page

5318

Location

England

Related Subject Headings

  • Sporozoites
  • Protozoan Proteins
  • Primary Cell Culture
  • Mice, Inbred C57BL
  • Mice
  • Malaria, Falciparum
  • Malaria Vaccines
  • Humans
  • Hepatocytes
  • Female
 

Citation

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Livingstone, M. C., Bitzer, A. A., Giri, A., Luo, K., Sankhala, R. S., Choe, M., … Dutta, S. (2021). In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP). Sci Rep, 11(1), 5318. https://doi.org/10.1038/s41598-021-84622-x
Livingstone, Merricka C., Alexis A. Bitzer, Alish Giri, Kun Luo, Rajeshwer S. Sankhala, Misook Choe, Xiaoyan Zou, et al. “In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP).Sci Rep 11, no. 1 (March 5, 2021): 5318. https://doi.org/10.1038/s41598-021-84622-x.
Livingstone MC, Bitzer AA, Giri A, Luo K, Sankhala RS, Choe M, et al. In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP). Sci Rep. 2021 Mar 5;11(1):5318.
Livingstone, Merricka C., et al. “In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP).Sci Rep, vol. 11, no. 1, Mar. 2021, p. 5318. Pubmed, doi:10.1038/s41598-021-84622-x.
Livingstone MC, Bitzer AA, Giri A, Luo K, Sankhala RS, Choe M, Zou X, Dennison SM, Li Y, Washington W, Ngauy V, Tomaras GD, Joyce MG, Batchelor AH, Dutta S. In vitro and in vivo inhibition of malaria parasite infection by monoclonal antibodies against Plasmodium falciparum circumsporozoite protein (CSP). Sci Rep. 2021 Mar 5;11(1):5318.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

March 5, 2021

Volume

11

Issue

1

Start / End Page

5318

Location

England

Related Subject Headings

  • Sporozoites
  • Protozoan Proteins
  • Primary Cell Culture
  • Mice, Inbred C57BL
  • Mice
  • Malaria, Falciparum
  • Malaria Vaccines
  • Humans
  • Hepatocytes
  • Female