Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein Is a Target of Protective Antibodies

Diego A. Espinosa, Gabriel M. Gutierrez, Maricarmen Rojas-Lopez, Amy R. Noe, Lirong Shi, Sze Wah Tse, Photini Sinnis, Fidel P Zavala

Research output: Contribution to journalArticle

Abstract

Studies in animals and human volunteers demonstrate that antibodies against the repeat-region of the Plasmodium circumsporozoite protein (CSP) abrogate sporozoite infection. However, the realization that the N-and C-terminal regions flanking the repeats play essential roles in parasite infectivity raised the possibility that they could be targeted by protective antibodies. We characterized a monoclonal antibody (mAb5D5) specific for the N-terminus of the P. falciparum CSP, which inhibits the proteolytic cleavage of the CSP, a key requirement for parasite infection of hepatocytes. Adoptive transfer of mAb5D5 strongly inhibits the in vivo infection of sporozoites expressing the N-terminus of P. falciparum CSP, and this protection is greatly enhanced when combined with antirepeat antibodies. Our results show that antibodies interfering with molecular processes required for parasite infectivity can exert a strong in vivo protective activity and indicate that pre-erythrocytic vaccines against Plasmodium should include the CSP N-terminal region.

Original languageEnglish (US)
Pages (from-to)1111-1119
Number of pages9
JournalJournal of Infectious Diseases
Volume212
Issue number7
DOIs
StatePublished - Oct 1 2015

Fingerprint

Plasmodium falciparum
Sporozoites
Antibodies
Parasites
Parasitic Diseases
Plasmodium
Adoptive Transfer
Infection
Volunteers
Hepatocytes
Proteins
Vaccines
Monoclonal Antibodies
Protozoan circumsporozoite protein

Keywords

  • Antibodies
  • CSP
  • malaria
  • P. falciparum
  • sporozoites
  • vaccine

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein Is a Target of Protective Antibodies. / Espinosa, Diego A.; Gutierrez, Gabriel M.; Rojas-Lopez, Maricarmen; Noe, Amy R.; Shi, Lirong; Tse, Sze Wah; Sinnis, Photini; Zavala, Fidel P.

In: Journal of Infectious Diseases, Vol. 212, No. 7, 01.10.2015, p. 1111-1119.

Research output: Contribution to journalArticle

Espinosa, Diego A. ; Gutierrez, Gabriel M. ; Rojas-Lopez, Maricarmen ; Noe, Amy R. ; Shi, Lirong ; Tse, Sze Wah ; Sinnis, Photini ; Zavala, Fidel P. / Proteolytic Cleavage of the Plasmodium falciparum Circumsporozoite Protein Is a Target of Protective Antibodies. In: Journal of Infectious Diseases. 2015 ; Vol. 212, No. 7. pp. 1111-1119.
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