Dados do Trabalho

Título

A novel Plasmodium vivax malaria vaccine: towards to phase 1/2 clinical trial

Introdução

Malaria is caused by Plasmodium parasites, which are transmitted through the bite of the Anopheles mosquito in tropical regions. The development of alternative tools to control malaria is increasingly important due to the emergence of drug-resistant parasites and insecticide-resistant mosquitoes. The most advanced malaria vaccine available today is Mosquirix®, also known as RTS,S. It is a recombinant vaccine based on the circumsporozoite protein (CSP) of P. falciparum, and does not offer any protection against P. vivax. In 2022, approximately 6.9 million cases of malaria were caused by P. vivax, primarily in the Southeast Asia and Americas regions (WHO malaria report 2023). In the present study, we used a recombinant hybrid polypeptide called PvCSP-All epitopes, which containing the conserved C-terminus of the P. vivax CSP and the three variant repeat domain (VK210, VK247 and P. vivax-like). This polypeptide was expressed using the yeast system Pichia pastoris.  

Objetivo (s)

For the development of the preclinical study and complete characterization of the target protein profile, a batch of active pharmaceutical ingredient (API) was produced at the University of Nebraska under GLP conditions.

Material e Métodos

A preliminary stability study of both the API and the vaccine formulation proposal was performed to evaluate physicochemical and antigenicity parameters for quality control at long-term (5°C) and accelerated (30°C) temperatures at 0, 7, 15, 30, 60, 90 and 180 days and the vaccine remained stable in the proposed formulation at 5 degrees for the 6 months of follow-up. In order to evaluate the vaccine potential of PvCSP-All epitopes, C57BL/6 mice were immunized with three doses of the protein formulated with different nanoemulsion-based adjuvants and a double-stranded RNA analogue that interacts with Toll-like receptor 3 (TLR3).  

Resultados e Conclusão

The humoral response was evaluated and a significant production of total IgG, IgG1 and IgG2c antibodies specific for both the PvCSP chimera and all subunits was observed in the immunized groups. In addition, an efficacy study was conducted using 5,000 Pb/PvVK210 sporozoites as a challenge, resulting in a best protection of the animals vaccinated with the nanoemulsion-based proposed formulation. Currently, safety and toxicity tests, immunogenicity studies in non-human primates and clinical experimental designs are underway. These experiments are being completed with a view to submission to ANVISA, requesting approval to start of the phase 1 clinical study.

Palavras Chave

Palavras-chaves: Malaria; CSP; vaccine; P. vivax