Last Updated: 02/12/2024
Comparative analysis of humoral and cellular responses induced by anti-malarial vaccine in adult C57Bl/6 mice, pregnant or not, and in weanlings
Objectives
*Original title in Portuguese: Análise comparativa das respostas humoral e celular induzidas por vacina anti-malárica em camundongos C57Bl/6 adultos, prenhas ou não, e em recém-desmamados
The main objective is to compare the cellular and humoral immune responses triggered by 2 doses of this same vaccine combined with Poly I:C, intramuscularly and 2 weeks apart, in adult or young C57Bl/6 mice, respectively with 8 or 3 weeks of age at the time of administration of the first dose of vaccine, in addition to effects on pregnant animals and their offspring.
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. Seven species of the Plasmodium parasite have already been described as capable of inducing malaria in humans. Plasmodium vivax (Pv) has the widest geographic distribution 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 prevalent in sub-Saharan 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 of 3 domains that contain motifs in repeats and epitopes of B cells. Considering the high immunogenicity of these repeats, DNA sequencing of the central domain from CSP showed that these repeats have different mutations according to their regions of origin. Recently, the research group of Dr. Irene Soares from FBC-FCF-USP developed a protective vaccine against malaria, called yPvCSP-All epitopes, in adult C57Bl/6 mice. Its construction was based on a recombinant protein expressed in yeast containing the central domain of the Pv CSP, and the 3 most frequent alleles (VK210, VK247 and P. vivax-like) in the world, in addition to the C-terminal region. The administration of this protein combined with the Poly I:C adjuvant induced the appearance of both T and antibody-secreting cells, as well as specific antibodies against the 3 PvCSP alleles after immunizations. However, we do not know whether this vaccine is capable of generating a similar degree of immunity in pregnant females and in newly weaned animals.
Jan 2020
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