Liposomes loaded with P. falciparum merozoite-derived proteins are highly immunogenic and produce invasion-inhibiting and anti-toxin antibodies.
The formulation of an effective vaccine against malaria is still a significant challenge and the induction of high anti-parasite antibody titers plus a sustained T cell response is mandatory for the success of such a vaccine. We have developed a nanoliposome-based structure which contains plasma membrane-associated proteins (PfMNP) of Plasmodium falciparum merozoites on its surface. Incorporation of parasite-derived proteins led to a significant increase in the size and dispersity of particles. Immunization of particles in BalbC and C57BL/6 mice led to high anti-MSP119 IgG titers (10(4)) after the first dose and reached a plateau (>10(6)) after the third dose. While very high titers were observed against the C-terminal domain of the vaccine candidate MSP1, only modest titers (≤10(3)) were detected against MSP2. The induced antibodies showed also a strong growth-inhibiting effect in reinvasion assays. In addition, PfMNP immunization generated antibodies which partially blocked the inflammatory response, probably by blocking TLR-induced activation of macrophages by malarial toxins such as GPI anchors. The results underline the potential of nanoliposome-based formulations as anti-malarial vaccines.
Institute of Biomedical Sciences, Brazil.
Wesley L
WL
Fotoran
Institute of Biomedical Sciences, Brazil.
Rachele M
RM
Santangelo
Institute of Biomedical Sciences, Brazil.
Márcia M
MM
Medeiros
Institute of Biomedical Sciences, Brazil.
Marcelle
M
Colhone
Institute of Biomedical Sciences, Brazil.
Pietro
P
Ciancaglini
Institute of Biomedical Sciences, Brazil.
Renato
R
Barboza
Institute of Biomedical Sciences, Brazil.
Claudio Romero Farias
CR
Marinho
Institute of Biomedical Sciences, Brazil.
Rodrigo Guerino
RG
Stábeli
Institute of Biomedical Sciences, Brazil. Electronic address: gwunder@usp.br.
Gerhard
G
Wunderlich
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000953:Antigens, Protozoan / Q000276:immunology*; D002460:Cell Line; D007074:Immunoglobulin G / Q000276:immunology; D008081:Liposomes; D017780:Malaria Vaccines; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D052940:Merozoites; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D008081:Liposomes; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins
GPI merozoite antigens; PfRH5; Plasmodium falciparum; Proteoliposome