Protection induced by malaria virus-like particles containing codon-optimized AMA-1 of Plasmodium berghei

Malar J. 2019 Dec 3;18(1):394. doi: 10.1186/s12936-019-3017-2.

Abstract

Background: Despite the extensive endeavours, developing an effective malaria vaccine remains as a great challenge. Apical membrane antigen 1 (AMA-1) located on the merozoite surface of parasites belonging to the genus Plasmodium is involved in red blood cell invasion.

Methods: Influenza virus-like particle (VLP) vaccines containing codon-optimized or native (non-codon optimized) AMA-1 from Plasmodium berghei were generated. VLP-induced protective immunity was evaluated in a mouse model.

Results: Mice immunized with VLP vaccine containing the codon-optimized AMA-1 elicited higher levels of P. berghei-specific IgG and IgG2a antibody responses compared to VLPs containing non-codon optimized AMA-1 before and after challenge infection. Codon-optimized AMA-1 VLP vaccination induced higher levels of CD4+ T cells, CD8+ T cells, B cells, and germinal centre cell responses compared to non-codon optimized AMA-1 VLPs. Importantly, the codon-optimized AMA-1 VLP vaccination showed lower body weight loss, longer survival and a significant decrease in parasitaemia compared to non-codon optimized VLP vaccination.

Conclusion: Overall, VLP vaccine expressing codon-optimized AMA-1 induced better protective efficacy than VLPs expressing the non-codon optimized AMA-1. Current findings highlight the importance of codon-optimization for vaccine use and its potential involvement in future malaria vaccine design strategies.

Keywords: Apical membrane antigen 1 (AMA-1); Codon-optimized; Plasmodium berghei; Vaccine; Virus-like particles.

MeSH terms

  • Animals
  • Antigens, Protozoan / therapeutic use*
  • Codon / immunology
  • Female
  • Malaria / prevention & control*
  • Malaria Vaccines / pharmacology*
  • Membrane Proteins / therapeutic use*
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / immunology*
  • Protozoan Proteins / therapeutic use*
  • Vaccines, Virus-Like Particle / pharmacology*

Substances

  • Antigens, Protozoan
  • Codon
  • Malaria Vaccines
  • Membrane Proteins
  • Protozoan Proteins
  • Vaccines, Virus-Like Particle
  • apical membrane antigen I, Plasmodium