Liposomes loaded with P. falciparum merozoite-derived proteins are highly immunogenic and produce invasion-inhibiting and anti-toxin antibodies

J Control Release. 2015 Nov 10:217:121-7. doi: 10.1016/j.jconrel.2015.08.045. Epub 2015 Aug 31.

Abstract

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.

Keywords: GPI merozoite antigens; PfRH5; Plasmodium falciparum; Proteoliposome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Protozoan / immunology*
  • Antigens, Protozoan / immunology*
  • Cell Line
  • Immunoglobulin G / immunology
  • Liposomes
  • Malaria Vaccines
  • Male
  • Membrane Proteins / immunology*
  • Merozoites
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Plasmodium falciparum*
  • Protozoan Proteins / immunology*

Substances

  • Antibodies, Protozoan
  • Antigens, Protozoan
  • Immunoglobulin G
  • Liposomes
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins