Malaria vaccine candidates displayed on novel virus-like particles are immunogenic and induce transmission-blocking activity

Abstract

The development of effective malaria vaccines remains a global health priority. Currently, the most advanced vaccine, known as RTS,S, has only shown modest efficacy in clinical trials. Thus, the development of more efficacious vaccines by improving the formulation of RTS,S for increased efficacy or to interrupt malaria transmission are urgently needed. The RTS,S vaccine is based on the presentation of a fragment of the sporozoite antigen on the surface of virus-like particles (VLPs) based on human hepatitis B virus (HBV). In this study, we have developed and evaluated a novel VLP platform based on duck HBV (known as Metavax) for malaria vaccine development. This platform can incorporate large and complex proteins into VLPs and is produced in a Hansenula cell line compatible with cGMP vaccine production. Here, we have established the expression of leading P. falciparum malaria vaccine candidates as VLPs. This includes Pfs230 and Pfs25, which are candidate transmission-blocking vaccine antigens. We demonstrated that the VLPs effectively induce antibodies to malaria vaccine candidates with minimal induction of antibodies to the duck-HBV scaffold antigen. Antibodies to Pfs230 also recognised native protein on the surface of gametocytes, and antibodies to both Pfs230 and Pfs25 demonstrated transmission-reducing activity in standard membrane feeding assays. These results establish the potential utility of this VLP platform for malaria vaccines, which may be suitable for the development of multi-component vaccines that achieve high vaccine efficacy and transmission-blocking immunity.

Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children

“…Recombinant MSP2 FC27 was expressed in E. coli 68 . PfAMA1 43 , full-length PfCSP 69 and Pfs230D1M 70 were previously generated via expression in the mammalian HEK293 cell expression system.…”

Novel Virus-Like Particle Vaccine Encoding the Circumsporozoite Protein of Plasmodium falciparum Is Immunogenic and Induces Functional Antibody Responses in Mice

“…We report for the first time, the production of a dS-based VLP that formed particles in the absence of excess unfused scaffold protein ( 44 , 45 ). Previously, we reported the expression of malaria transmission-blocking vaccine antigens Pfs230 and Pfs25 as VLPs using the duck HBV platform ( 19 , 21 ). However, in those cases, the VLPs were formed with excess dS protein and, as a result, only a minority of the total protein content was formed by the vaccine antigen.…”

“…Here we describe the production and characterization of a novel VLP-based vaccine candidate that displays CSP on the surface. We used the membrane integral small surface protein (dS) of the duck hepatitis B virus (DHBV) as a VLP scaffold protein (19)(20)(21). As a proof-of-concept for this vaccine platform, the same truncated form of CSP that is included in RTS,S (central-repeat and C-terminal regions of the protein) was selected as the malaria vaccine antigen and was genetically fused to the dS.…”

Use of Protamine in Nanopharmaceuticals—A Review

“…It has been shown that VLP-L2 vaccines elicit antibodies with a broad and efficient level of protection against diverse HPV types [88]. VLPs have also been shown to induce immunity as vaccine delivery systems against malaria and arthropod-borne viruses [242,243], and Caldeira et al have discussed their use as cancer vaccines [244].…”