A Plasmodium falciparum candidate vaccine based on a six-antigen polyprotein encoded by recombinant poxviruses.
Proc Natl Acad Sci U S A
; 101(1): 290-5, 2004 Jan 06.
Article
in En
| MEDLINE
| ID: mdl-14694197
ABSTRACT
To generate broadly protective T cell responses more similar to those acquired after vaccination with radiation-attenuated Plasmodium falciparum sporozoites, we have constructed candidate subunit malaria vaccines expressing six preerythrocytic antigens linked together to produce a 3240-aa-long polyprotein (L3SEPTL). This polyprotein was expressed by a plasmid DNA vaccine vector (DNA) and by two attenuated poxvirus vectors, modified vaccinia virus Ankara (MVA) and fowlpox virus of the FP9 strain. MVAL3SEPTL boosted anti-thrombospondin-related adhesive protein (anti-TRAP) and anti-liver stage antigen 1 (anti-LSA1) CD8(+) T cell responses when primed by single antigen TRAP- or LSA1-expressing DNAs, respectively, but not by DNA-L3SEPTL. However, prime boost regimes involving two heterologous viral vectors expressing L3SEPTL induced a strong cellular response directed against an LSA1 peptide located in the C-terminal region of the polyprotein. Peptide-specific T cells secreted IFN-gamma and were cytotoxic. IFN-gamma-secreting T cells specific for each of the six antigens were induced after vaccination with L3SEPTL, supporting the use of polyprotein inserts to induce multispecific T cells against P. falciparum. The use of polyprotein constructs in nonreplicating poxviruses should broaden the target antigen range of vaccine-induced immunity and increase the number of potential epitopes available for immunogenetically diverse human populations.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Plasmodium falciparum
/
Malaria, Falciparum
/
Malaria Vaccines
Limits:
Animals
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2004
Type:
Article
Affiliation country:
United kingdom