Abstract

BackgroundDespite 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.MethodsInfluenza 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.ResultsMice 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.ConclusionOverall, 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.

Highlights

  • Despite the extensive endeavours, developing an effective malaria vaccine remains as a great chal‐ lenge

  • Malaria vaccines can be aimed to the various stages of antigens of the parasite life cycle, especially the stage that involves host red blood cells (RBCs) [4, 5]

  • There are several malaria vaccines under development, with the most promising of them being apical membrane antigen 1 (AMA-1) derived from asexual bloodstage antigens found on the merozoite surface

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Summary

Introduction

Despite the extensive endeavours, developing an effective malaria vaccine remains as a great chal‐ lenge. 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. An estimated 219 million cases of malaria have been reported in 87 countries in 2017 [1]. The World Health Organization (WHO) estimates over one million deaths by malaria infection each year, which is a severe public health problem [2]. Malaria vaccines can be aimed to the various stages of antigens of the parasite life cycle, especially the stage that involves host red blood cells (RBCs) [4, 5]. There are several malaria vaccines under development, with the most promising of them being apical membrane antigen 1 (AMA-1) derived from asexual bloodstage antigens found on the merozoite surface. AMA-1 is a protein of apicomplexan parasites that is essential for

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