TY - JOUR

T1 - Antigenicity and immunogenicity of a novel Plasmodium vivax circumsporozoite derived synthetic vaccine construct

AU - Céspedes, Nora

AU - Jiménez, Eliécer

AU - Lopez-Perez, Mary

AU - Rubiano, Kelly

AU - Felger, Ingrid

AU - Alonso, Pedro

AU - Arévalo-Herrera, Myriam

AU - Corradin, Giampietro

AU - Herrera, Sócrates

N1 - Copyright © 2014 Elsevier Ltd. All rights reserved.

PY - 2014/5/30

Y1 - 2014/5/30

N2 - 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.

AB - 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.

KW - Adjuvants, Immunologic

KW - Amino Acid Sequence

KW - Animals

KW - Antibodies, Protozoan

KW - Antigens, Protozoan

KW - Cell Line, Tumor

KW - Humans

KW - Immune Sera

KW - Immunity, Humoral

KW - Malaria Vaccines

KW - Malaria, Vivax

KW - Mice, Inbred C3H

KW - Molecular Sequence Data

KW - Plasmodium vivax

KW - Protozoan Proteins

KW - Vaccines, Synthetic

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.vaccine.2014.04.007

DO - 10.1016/j.vaccine.2014.04.007

M3 - Journal article

C2 - 24731811

VL - 32

SP - 3179

EP - 3186

JO - Vaccine

JF - Vaccine

SN - 0264-410X

IS - 26

ER -