Abstract
With the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (PPV-VLPs) carrying the CD8+ T cell epitope (SYVPSAEQI) of the circumsporozoite (CS) protein from Plasmodium yoelii fused to the PPV VP2 capsid protein (PPV-PYCS), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. As a proof-of concept, we have characterized the anti-CS CD8+ T cell response elicited by these hybrid PPV-VLPs in BALB/c mice after immunizations with the protein PPV-PYCS administered alone or in combination with recombinant vaccinia virus (VACV) vectors from the Western Reserve (WR) and modified virus Ankara (MVA) strains expressing the entire P. yoelii CS protein. The results of different immunization protocols showed that the combination of PPV-PYCS prime/poxvirus boost was highly immunogenic, inducing specific CD8+ T cell responses to CS resulting in 95% reduction in liver stage parasites two days following sporozoite challenge. In contrast, neither the administration of PPV-PYCS alone nor the immunization with the vectors given in the order poxvirus/VLPs was as effective. The immune profile induced by VLPs/MVA boost was associated with polyfunctional and effector memory CD8+ T cell responses. These findings highlight the use of recombinant parvovirus PPV-PYCS particles as priming agents and poxvirus vectors, like MVA, as booster to enhance specific CD8+ T cell responses to Plasmodium antigens and to control infection. These observations are relevant in the design of T cell-inducing vaccines against malaria.
Highlights
The development of a malaria vaccine is a major goal in the fight against infectious diseases, as infection with Plasmodium falciparum causes an estimated 225 million cases of malaria and 781,000 deaths from the disease worldwide, mostly among children in Africa [1]
To study the ability of PPV-PYCS to induce a specific anti-CS T cell immune response, and to test whether the achieved immune response could be enhanced after booster with a replication competent vaccinia virus (VACV) recombinant from Western Reserve (WR) strain expressing the complete CS protein (VV-PYCS), we immunized groups of BALB/c mice (5 per group) with PPV-PYCS given subcutaneously (s.c) (10 or 50 mg/ per mouse), and boosted 14 days later with 107 pfu/mouse of VV-PYCS by the same route
While one of the main interests in the malaria vaccine field is to develop immunogens based on proteins for safety considerations, the immune response triggered by proteins is generally weak with a bias for Th2 type
Summary
The development of a malaria vaccine is a major goal in the fight against infectious diseases, as infection with Plasmodium falciparum causes an estimated 225 million cases of malaria and 781,000 deaths from the disease worldwide, mostly among children in Africa [1] Progress in this direction has been obtained with the demonstration in phase 2 clinical trials that the administration of an anti-sporozoite vaccine based on the parasite CS protein fused with the hepatitis B antigen (referred as RTS,S) in combination with the adjuvants AS01 and AS02 generates in children and infants around 50% clinical efficacy against malaria [2,3,4] [5]. The limited protection far obtained with the RTS,S vaccine, suggest the need to improve the efficacy of this malaria vaccine
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
