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Comparison of the immune responses induced by soluble and particulate Plasmodium vivax circumsporozoite vaccine candidates formulated in AS01 in rhesus macaques.
- Source :
-
Vaccine [Vaccine] 2013 Dec 16; Vol. 31 (52), pp. 6216-24. Date of Electronic Publication: 2013 Oct 19. - Publication Year :
- 2013
-
Abstract
- We have designed a pre-erythrocytic vaccine candidate based on the Plasmodium vivax circumsporozoite (CSV) protein, which includes its N- and C-terminal parts and a truncated region containing repeat sequences from both the VK210 and the VK247 P. vivax subtypes. Two versions of this vaccine candidate were made: a soluble recombinant protein expressed in Escherichia coli, designated VMP001 and a particulate antigen expressed in Saccharomyces cerevisiae, designated CSV-S,S. The latter is composed of CSV-S, a fusion protein between VMP001 and hepatitis B surface antigen (HBsAg), and free HBsAg co-expressed in yeast and self-assembling into mixed particles. Both antigen versions, adjuvanted with AS01, were shown to be immunogenic in rhesus monkeys. CSV-S,S/AS01 induced higher levels of VMP001-specific antibodies than did VMP001/AS01. Antibody responses against the N- and C-terminal regions of CSV and the VK210 repeat motif were of a similar magnitude following immunization with either the soluble or the particulate antigen. However, antibodies against the AGDR region, a potentially protective B cell epitope, were only detected after immunization with CSV-S,S. Analysis of the induced CD4(+) T cells highlighted different cytokine profiles depending on the antigen form. These results warrant further clinical evaluation of these two vaccine candidates to assess the added value of a particulate versus soluble form of CSV, in terms of both immunogenicity and protective efficacy.<br /> (Copyright © 2013 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Antibodies, Protozoan blood
CD4-Positive T-Lymphocytes immunology
Cytokines metabolism
Escherichia coli genetics
Gene Expression
Macaca mulatta
Malaria Vaccines administration & dosage
Malaria Vaccines genetics
Plasmodium vivax genetics
Protozoan Proteins genetics
Saccharomyces cerevisiae genetics
Vaccines, Subunit administration & dosage
Vaccines, Subunit genetics
Vaccines, Subunit immunology
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Vaccines, Virus-Like Particle administration & dosage
Vaccines, Virus-Like Particle genetics
Vaccines, Virus-Like Particle immunology
Adjuvants, Immunologic administration & dosage
Malaria Vaccines immunology
Plasmodium vivax immunology
Protozoan Proteins immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2518
- Volume :
- 31
- Issue :
- 52
- Database :
- MEDLINE
- Journal :
- Vaccine
- Publication Type :
- Academic Journal
- Accession number :
- 24144477
- Full Text :
- https://doi.org/10.1016/j.vaccine.2013.10.041