A proof-of-concept study for the design of a VLP-based combinatorial HPV and placental malaria vaccine

Abstract

In Africa, cervical cancer and placental malaria (PM) are a major public health concern. There is currently no available PM vaccine and the marketed Human Papillomavirus (HPV) vaccines are prohibitively expensive. The idea of a combinatorial HPV and PM vaccine is attractive because the target population for vaccination against both diseases, adolescent girls, would be overlapping in Sub-Saharan Africa. Here we demonstrate proof-of-concept for a combinatorial vaccine utilizing the AP205 capsid-based virus-like particle (VLP) designed to simultaneously display two clinically relevant antigens (the HPV RG1 epitope and the VAR2CSA PM antigen). Three distinct combinatorial VLPs were produced displaying one, two or five concatenated RG1 epitopes without obstructing the VLP’s capacity to form. Co-display of VAR2CSA was achieved through a split-protein Tag/Catcher interaction without hampering the vaccine stability. Vaccination with the combinatorial vaccine(s) was able to reduce HPV infection in vivo and induce anti-VAR2CSA IgG antibodies, which inhibited binding between native VAR2CSA expressed on infected red blood cells and chondroitin sulfate A in an in vitro binding-inhibition assay. These results show that the Tag/Catcher AP205 VLP system can be exploited to make a combinatorial vaccine capable of eliciting antibodies with dual specificity.

Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies

“…Recently, methods that enable coupling of complex antigens to pre-formed VLP have been developed, employing the SpyTag/SpyCatcher conjugation system [31,33,34]. Employed in mice, these VLP vaccines have induced high and stable IgG levels against microbial antigens, including malaria antigens [48][49][50][51].…”

A Universal Plug-and-Display Vaccine Carrier Based on HBsAg VLP to Maximize Effective Antibody Response

“…Even though AP205 VLPs are under investigation as carrier for various vaccine candidates (24)(25)(26)(27)(28)(29), no safety data in humans is available, and such lack of clinical information can slow down the development of new vaccines based on this VLP platform. By contrast, using a VLP with a well-established safety profile as a vaccine scaffold could accelerate the pre-clinical to clinical transition.…”

Bioengineered Polyhydroxyalkanoates as Immobilized Enzyme Scaffolds for Industrial Applications

“…The formation of VLPs is a selfassembling process of the viral capsid, which potentially mimics the general structure of the parental virus. However, VLPs do not contain nucleic acids, and, thus, there is no risk of causing infection (Charlton Hume et al, 2019;Janitzek et al, 2019). The CP subunits can be genetically modified for bioconjugation, enabling molecules of interest to be densely displayed or encapsulated in homogeneous spatial orientation (Tan and Jiang, 2017;Charlton Hume et al, 2019).…”

“…The CP subunits can be genetically modified for bioconjugation, enabling molecules of interest to be densely displayed or encapsulated in homogeneous spatial orientation (Tan and Jiang, 2017;Charlton Hume et al, 2019). VLPs have made significant advances in various fields, from vaccinology to industrial uses due to their promising characteristics, including monodispersed particle size distribution, defined geometric surfaces, biosafety, and functional programmability (Mohsen et al, 2017;Janitzek et al, 2019). Additionally, the viral capsids are stable over a wide range of environmental conditions, such as temperatures and pHs, which make them suitable for different applications, including industrial biocatalysis (Stanley, 2014;Koch et al, 2015;Brasch et al, 2017;Torbensen et al, 2019).…”