Malaria in pregnancy: the relevance of animal models for vaccine development

Abstract

Malaria during pregnancy due to Plasmodium falciparum or P. vivax is a major public health problem in endemic areas, with P. falciparum causing the greatest burden of disease. Increasing resistance of parasites and mosquitoes to existing tools, such as preventive antimalarial treatments and insecticide-treated bed nets respectively, is eroding the partial protection that they offer to pregnant women. Thus, development of effective vaccines against malaria during pregnancy is an urgent priority. Relevant animal models that recapitulate key features of the pathophysiology and immunology of malaria in pregnant women could be used to accelerate vaccine development. This review summarizes available rodent and nonhuman primate models of malaria in pregnancy, and discusses their suitability for studies of biologics intended to prevent or treat malaria in this vulnerable population.

Contribution of Murine Models to the Study of Malaria During Pregnancy

“…As such, refinement of experimental design and standardization of methodology is necessary for the improvement of such models (BOX 1). Resolving these gaps will certainly enrich research in the field, possibly reaffirming the usage of murine models to address more specific and complex questions implicit in drug preclinical trials and vaccine development (Doritchamou et al, 2017). Research in the field has indeed overcome several milestones due to the usage of rodent models with much progress that is still to come.…”

Malaria vaccine research & innovation: the intersection of IA2030 and zero malaria

“…More than two decades ago, antibodies to VAR2CSA, a member of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family, were associated with protection, identifying VAR2CSA as a promising vaccine target 21 . Placenta malaria vaccine (PMVs) research and innovation continues to progress 6 , including through the development of new animal models 22 and down-selection of lead PVM candidates 23 .…”

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“…When malaria occurs in a pregnant woman, it can lead to various conditions such as abortion and pre-term delivery (both due to the release of prostaglandins due to fever caused in malaria), [50] cerebral malaria, intrauterine growth retardation, and fetal, and maternal death due to maternal anemia. [52,53] The placenta in the mother has decidual vessels to which the P. genus has a very high liking, so it gets attracted to it highly. Therefore, the occurrence of malaria during pregnancy is very high along with human immunodeficiency virus infection.…”

“…[50,54] P. vivax also causes malaria in pregnancy leading to maternal anemia and low birth weight, but, the severity of the disease is less than that produced by the P. falciparum species. [52]…”

“…The multiplication of the parasites in the placenta can lead to the formation of an inflammatory infiltrate in the spaces between the villi which ultimately leads to severe, maternal anemia, and low birth weight in the newborn babies. [52] Immunity against VAR2CSA is developed naturally with successive pregnancies which help in the protection against the adverse birth outcomes. Thus, development of a vaccine against VAR2CSA could be a beneficial way to decrease the adverse consequences taking place during malaria in pregnancy.…”