Forskning ved Københavns Universitet - Københavns Universitet

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Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite derived synthetic vaccine construct

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Nora Céspedes
  • Eliécer Jiménez
  • Lopez-Perez, Mary
  • Kelly Rubiano
  • Ingrid Felger
  • Pedro Alonso
  • Myriam Arévalo-Herrera
  • Giampietro Corradin
  • Sócrates Herrera

BACKGROUND: The circumsporozoite (CS) protein is a major malaria sporozoite surface antigen currently being considered as vaccine candidate. Plasmodium vivax CS (PvCS) protein comprises a dimorphic central repeat fragment flanked by conserved regions that contain functional domains involved in parasite invasion of host cells. The protein amino (N-terminal) flank has a cleavage region (region I), essential for proteolytic processing prior to parasite invasion of liver cells.

METHODS: We have developed a 131-mer long synthetic polypeptide (LSP) named PvNR1R2 that includes the N-terminal flank and the two natural repeat variant regions known as VK210 and VK247. We studied the natural immune response to this region in human sera from different malaria-endemic areas and its immunogenicity in mice.

RESULTS: PvNR1R2 was more frequently recognized by sera from Papua New Guinea (PNG) (83%) than by samples from Colombia (24%) when tested by ELISA. The polypeptide formulated in Montanide ISA51 adjuvant elicited strong antibody responses in both C3H and CB6F1 mice strains. Antibodies from immunized mice as well as affinity-purified human IgG reacted with native protein by IFA test. Moreover, mouse immune sera induced strong (90%) in vitro inhibition of sporozoite invasion (ISI) of hepatoma cell lines.

CONCLUSIONS: These results encourage further studies in non-human primates to confirm the elicitation of sporozoite invasion blocking antibodies, to assess cell mediated immune responses and the protective efficacy of this polypeptide.

OriginalsprogEngelsk
TidsskriftVaccine
Vol/bind32
Udgave nummer26
Sider (fra-til)3179-86
Antal sider8
ISSN0264-410X
DOI
StatusUdgivet - 30 maj 2014
Eksternt udgivetJa

ID: 169006474