Virus-Like Particle (VLP) Plus Microcrystalline Tyrosine (MCT) Adjuvants Enhance Vaccine Efficacy Improving T and B Cell Immunogenicity and Protection against Plasmodium berghei/vivax

Abstract

Vaccination is the most effective prophylactic tool against infectious diseases. Despite continued efforts to control malaria, the disease still generally represents a significant unmet medical need. Microcrystalline tyrosine (MCT) is a well described depot used in licensed allergy immunotherapy products and in clinical development. However, its proof of concept in prophylactic vaccines has only recently been explored. MCT has never been used in combination with virus-like particles (VLPs), which are considered to be one of the most potent inducers of cellular and humoral immune responses in mice and humans. In the current study we assessed the potential of MCT to serve as an adjuvant in the development of a vaccine against malaria either alone or combined with VLP using Plasmodium vivax thrombospondin-related adhesive protein (TRAP) as a target antigen. We chemically coupled PvTRAP to VLPs derived from the cucumber mosaic virus fused to a universal T-cell epitope of the tetanus toxin (CMVtt), formulated with MCT and compared the induced immune responses to PvTRAP formulated in PBS or Alum. The protective capacity of the various formulations was assessed using Plasmodium berghei expressing PvTRAP. All vaccine formulations using adjuvants and/or VLP increased humoral immunogenicity for PvTRAP compared to the antigen alone. The most proficient responder was the group of mice immunized with the vaccine formulated with PvTRAP-VLP + MCT. The VLP-based vaccine formulated in MCT also induced the strongest T cell response and conferred best protection against challenge with recombinant Plasmodium berghei. Thus, the combination of VLP with MCT may take advantage of the properties of each component and appears to be an alternative biodegradable depot adjuvant for development of novel prophylactic vaccines.

Microcrystalline Tyrosine (MCT®): A Depot Adjuvant in Licensed Allergy Immunotherapy Offers New Opportunities in Malaria

“…Percent parasitaemia was used to calculate the time required to reach a blood-stage infection of 1% or time to 1% parasitaemia. This was predicted using a linear regression model as described previously [ 26 , 28 , 30 , 31 ]. Briefly, blood parasite counts were obtained for 6 consecutive days starting on day 4 after the challenge.…”

Recent Advances in the Use of Plant Virus-Like Particles as Vaccines

“…As alternatives to genetic fusions, other approaches can result in antigen presentation, such as chemical coupling or physical binding of the antigen to the VLP surface using binding partner molecules. Successful examples of the generation of vaccines using the chemical or enzymatic coupling of whole antigens include studies of experimental vaccines against Francisella tularensis [42], influenza [43], Yersinia pestis [44], Plasmodium vivax [45], and Zika virus [46].…”

“…Vaccine formulations containing VLPs increased antibody production against TRAP compared to that produced by the antigen alone. The VLP-based vaccine formulated with MCT conferred significant protection in the challenge test with recombinant P. berghei, suggesting that MCT can be used as an advantageous adjuvant alternative for prophylactic VLP vaccines [45].…”

Vaccination Against Amyloidogenic Aggregates in Pancreatic Islets Prevents Development of Type 2 Diabetes Mellitus

“…Up-to-date VLP-based vaccines already exist on the market, such as against human papilloma virus and against hepatitis B [28], and more are in clinical trials [29,30]. We have previously proven that VLPs can also be adopted as platform against amyloidogenic aggregates [31], chronic [32][33][34], allergic [35,36] and infection diseases [26,37,38]. In addition to humans, VLPs were successfully used as vaccines in companion animals [35,39,40].…”