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Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate
Journal article   Open access   Peer reviewed

Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of Recombinant Pfs25, a Leading Transmission-Blocking Vaccine Candidate

Elizabeth M. Parzych, Kazutoyo Miura, Aarti Ramanathan, Carole A. Long and James M. Burns
Infection and immunity, v 86(1)
19 Dec 2017
DOI: https://doi.org/10.1128/IAI.00486-17
PMID: 28993460
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191234View
Accepted (AM)Open Access (License Unspecified),  Open
url
https://doi.org/10.1128/IAI.00486-17View
Published, Version of Record (VoR) Open

Abstract

malaria Microbial Immunity and Vaccines MSP8 carrier protein subunit vaccines transmission blocking
Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multiantigen vaccine. Attempting to resolve these issues, we focused on the use of highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that a genetic fusion of the C-terminal 19-kDa fragment of merozoite surface protein 1 (MSP1 19 ) to P. falciparum MSP8 ( Pf MSP8) facilitated antigen production and folding and the induction of neutralizing antibodies to conformational B cell epitopes of MSP1 19 . Here, using the Pf MSP1/8 construct, we further optimized the recombinant Pf MSP8 (r Pf MSP8) carrier by the introduction of two cysteine-to-serine substitutions (CΔS) to improve the yield of the monomeric product. We then sought to test the broad applicability of this approach using the transmission-blocking vaccine candidate Pf s25. The production of r Pf s25-based vaccines has presented challenges. Antibodies directed against the four highly constrained epidermal growth factor (EGF)-like domains of Pf s25 block sexual-stage development in mosquitoes. The sequence encoding mature Pf s25 was codon harmonized for expression in Escherichia coli . We produced a r Pf s25- Pf MSP8 fusion protein [r Pf s25/8(CΔS)] as well as unfused, mature r Pf s25. r Pf s25 was purified with a modest yield but required the incorporation of refolding protocols to obtain a proper conformation. In comparison, chimeric r Pf s25/8(CΔS) was expressed and easily purified, with the Pf s25 domain bearing the proper conformation without renaturation. Both antigens were immunogenic in rabbits, inducing IgG that bound native Pf s25 and exhibited potent transmission-reducing activity. These data further demonstrate the utility of Pf MSP8 as a parasite-specific carrier protein to enhance the production of complex malaria vaccine targets.

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12 citations in Web of Science
12 citations in Scopus

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
Infectious Diseases
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