Blood stage merozoite surface protein conjugated to nanoparticles induce potent parasite inhibitory antibodies.

Abstract:

:In this proof-of-concept study we report the use of <15 nm, water soluble, inorganic nanoparticles as a vaccine delivery system for a blood stage malaria vaccine. The recombinant malarial antigen, Merozoite Surface Protein 1 (rMSP1) of Plasmodium falciparum served as the model vaccine. The rMSP1 was covalently conjugated to polymer-coated quantum dot CdSe/ZnS nanoparticles (QDs) via surface carboxyl groups, forming rMSP1-QDs. Anti-MSP1 antibody responses induced by rMSP1-QDs were found to have 2-3 log higher titers than those obtained with rMSP1 administered with the conventional adjuvants, Montanide ISA51 and CFA. Moreover, the immune responsiveness and the induction of parasite inhibitory antibodies were significantly superior in mice injected with rMSP1-QDs. The rMSP1-QDs delivered via intra-peritoneal (i.p.), intra-muscular (i.m.), and subcutaneous (s.c.) routes were equally efficacious. The high level of immunogenicity exhibited by the rMSP1-QDs was achieved without further addition of other adjuvant components. Bone marrow derived dendritic cells were shown to efficiently take up the nanoparticles leading to their activation and the expression/secretion of key cytokines, suggesting that this may be a mode of action for the enhanced immunogenicity. This study provides promising results for the use of water soluble, inorganic nanoparticles (<15 nm) as potent vehicles/platforms to enhance the immunogenicity of polypeptide antigens in adjuvant-free immunizations.

journal_name

Vaccine

journal_title

Vaccine

authors

Pusic K,Xu H,Stridiron A,Aguilar Z,Wang A,Hui G

doi

10.1016/j.vaccine.2011.09.070

subject

Has Abstract

pub_date

2011-11-08 00:00:00

pages

8898-908

issue

48

eissn

0264-410X

issn

1873-2518

pii

S0264-410X(11)01489-7

journal_volume

29

pub_type

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