Comparative analysis of humoral and cellular responses induced by vaccination with the recombinant protein yPvCSP-All epitopes combined with Poly I:C or Alum

Malaria is a parasitic disease of global public order, as it afflicts hundreds of millions of people in tropical regions, causing about 0.5 million deaths annually. Five species of the Plasmodium parasite have already been described as capable of inducing malaria in humans. Plasmodium vivax (Pv) has the highest worldwide prevalence among species, including in Brazil. Generally, the symptoms induced by infection with Pv are milder than those presented by the disease caused by Plasmodium falciparum (Pf), which is more frequent in Africa. A relentless search for a malaria vaccine has been going on for decades. Most vaccine formulations that have demonstrated efficacy in pre-clinical trials or in early stages of clinical trials against malaria prioritize an immune response directed against targets of pre-erythrocytic forms of the parasite. The most immunogenic protein at this stage of the parasite’s life is the circumsporozoite protein (CSP), whose structure is composed by 3 domains that contain motifs in B cell repeats and epitopes. Considering the high immunogenicity of these repeats, DNA sequencing of the central domain of CSP showed that these repeats have different mutations according to their regions of origin. Recently, the research group of Dr. Irene Soares from FBC-FCFUSP generated a protective vaccine against malaria in mice, called yPvCSP-All epitopes. Its construction was based on a recombinant protein from the central domain of Pv CSP, containing the 3 most frequent alleles (VK210, VK247 and P. vivax-like) in the world. Associated with this protective response, the presence of antibodies and T cells against the 3 alleles after immunizations was detected. This excellent result was obtained from the administration of yPvCSP-All epitopes with Poly I:C adjuvant in mice. Few adjuvants have been licensed for use in humans so far and the most frequently used is aluminum hydroxide, known as Alum. 

Project details

Vaccines (Immune Correlates)

Oct 2021

Brazil

Towards a vaccine for Plasmodium vivax