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Immunogenicity of Plasmodium falciparum and Plasmodium vivax circumsporozoite protein repeat multiple antigen
V Udhayakumar1, A Saekhou, S Fang
1Molecular Vaccine Section, Centers for Disease Control and Prevention, Atlanta, GA 30084, USA.
Abstract:
In this study we characterized the immunogenic properties of three different multispecies multiple antigen constructs (MACs) carrying the circumsporozoite protein (CSP) repeats of human malaria parasites, Plasmodium falciparum and P. vivax. We synthesized tetrameric MACs containing the antigenic repeats from the CSP of P. vivax-like parasite in two arms and CSP repeat sequences of either P. vivax type-1 (vivax-like/vivax type-1 MAC), P. vivax type-2 (vivax-like/vivax type-2 MAC), or P. falciparum (vivax-like/falciparum MAC) in the other two arms. Mice of four different genetic backgrounds (H-2a, H-2b, H-2d, and H-2k) were immunized with these MACs in Freund's adjuvant. All three MAC preparations were found to elicit antibodies to P. vivax-like CSP repeats in B10.BR, B10.A, and C57BL/6 mice. On the other hand, in B10.D2 mice only vivax-like/vivax type-1 MAC, but not the other two MACs induced antibodies to the P. vivax-like CSP repeats. In mice immunized with vivax-like/vivax type-1 MAC, antibodies to P. vivax type-1 CS repeat peptides were induced in B10.BR, B10.A, and C57BL/6 mice, but not in B10.D2 mice. Antibody responses to P. vivax type-2 repeats were not induced in any of the four strains of mice that were immunized with vivax-like/vivax type-2 MAC. While B10.BR, B10.A, and C57BL/6 mice produced antibodies to NANP repeats of P. falciparum CSP following immunization with vivax-like/falciparum MAC, B10.D2 mice failed to elicit antibodies to this repeat. All the sera that showed positive reactivity to peptides in enzyme-linked immunosorbent assay were found to react with sporozoites by IFA. In conclusion, these results showed that naturally immunogenic epitopes from different species of malaria parasites can be incorporated in a single vaccine construct to induce immune responses against multiple epitopes.
Insights
This study developed novel malaria vaccine constructs (MACs) by combining antigen repeats from different Plasmodium species. These constructs successfully induced antibodies against multiple malaria parasite epitopes in mice, showing potential for broad-spectrum malaria vaccines.
Area of Science:
- Immunology
- Vaccinology
- Parasitology
Background:
- Malaria remains a significant global health challenge, necessitating the development of effective vaccines.
- Current vaccine strategies often target specific Plasmodium species, highlighting the need for broader protection.
- Multispecies multiple antigen constructs (MACs) offer a promising approach to induce immunity against diverse malaria parasite strains.
Purpose of the Study:
- To characterize the immunogenic properties of three distinct multispecies multiple antigen constructs (MACs).
- To evaluate antibody responses against Plasmodium falciparum and Plasmodium vivax circumsporozoite protein (CSP) repeats in mice with different genetic backgrounds.
- To assess the potential of a single vaccine construct to elicit immune responses against multiple malaria parasite epitopes.
Main Methods:
- Synthesis of tetrameric MACs incorporating CSP repeat sequences from P. vivax-like, P. vivax type-1, P. vivax type-2, and P. falciparum.
- Immunization of mice (H-2a, H-2b, H-2d, H-2k) with MACs formulated in Freund's adjuvant.
- Antibody detection using enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay (IFA) on sporozoites.
Main Results:
- All three MACs elicited antibodies to P. vivax-like CSP repeats in most mouse strains, with variations observed in B10.D2 mice.
- Antibodies to P. vivax type-1 CSP repeats were induced in specific mouse strains, while responses to P. vivax type-2 repeats were not observed.
- Immunization with the P. falciparum-containing MAC induced antibodies to P. falciparum CSP repeats in most mouse strains, with limited response in B10.D2 mice.
- Positive ELISA reactivity correlated with sporozoite recognition by IFA, confirming the functional antibody response.
Conclusions:
- Naturally immunogenic epitopes from different malaria parasite species can be combined into a single vaccine construct.
- These MACs demonstrate the potential to induce immune responses against multiple malaria epitopes.
- The study provides valuable insights into the design of broadly protective malaria vaccines targeting diverse Plasmodium strains.