Abstract
Malaria continues being a high-impact disease regarding public health worldwide; the WHO report for malaria in 2018 estimated that ~219 million cases occurred in 2017, mostly caused by the parasite Plasmodium falciparum. The disease cost the lives of more than 400,000 people, mainly in Africa. In spite of great efforts aimed at developing better prevention (i.e., a highly effective vaccine), diagnosis, and treatment methods for malaria, no efficient solution to this disease has been advanced to date. The Fundación Instituto de Inmunología de Colombia (FIDIC) has been developing studies aimed at furthering the search for vaccine candidates for controlling P. falciparum malaria. However, vaccine development involves safety and immunogenicity studies regarding their formulation in animal models before proceeding to clinical studies. The present work has thus been aimed at evaluating the safety and immunogenicity of a mixture of 23 chemically synthesised, modified peptides (immune protection-inducing protein structure (IMPIPS)) derived from different P. falciparum proteins. Single and repeat dose assays were thus used with male and female BALB/c mice which were immunised with the IMPIPS mixture. It was found that single and repeat dose immunisation with the IMPIPS mixture was safe, both locally and systemically. It was observed that the antibodies so stimulated recognised the parasite's native proteins and inhibited merozoite invasion of red blood cells in vitro when evaluating the humoral immune response induced by the IMPIPS mixture. Such results suggested that the IMPIPS peptide mixture could be a safe candidate to be tested during the next stage involved in developing an antimalarial vaccine, evaluating local safety, immunogenicity, and protection in a nonhuman primate model.
Highlights
Malaria represents one of the greatest public health problems worldwide
The single dose local tolerance study was aimed at evaluating the site exposed to the formulation 72 h postimmunisation; no adverse reactions such as erythema, oedema, eschar, or necrosis were observed in the mice immunised with the immune protection-inducing protein structures (IMPIPS) mixture+Physiological saline solution (PSS) or in those immunised with IMPIPS +adjuvant
Male and female mice immunised with the IMPIPS peptide mixture+PSS or IMPIPS+adjuvant gained weight and increased their weekly food consumption, and their body temperature was within established parameters [56], thereby supporting the idea that the IMPIPS mixture did not affect physiology
Summary
Malaria represents one of the greatest public health problems worldwide. According to the World Health Organization (WHO), ~219 million new malaria-related cases occurred in 2017 accompanied by ~435,000 deaths. The African continent was the most affected region in the world (92% of cases and 93% of deaths) [1]. The Global Technical Strategy for Malaria 2016-2030 (WHO) has suggested reducing malarial incidence and mortality by at least 90% and eliminating it in at least 35 countries by 2030 through prevention, diagnosis, and treatment strategies [2]. No significant progress has been observed to date regarding the reduction of cases of malaria worldwide despite the differing strategies used for combating this disease (using insecticide-impregnated mosquito nets for controlling the vector, chemoprophylaxis, and case management) [1, 2].
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