Interferon-γ, a valuable surrogate marker of Plasmodium falciparum pre-erythrocytic stages protective immunity

Abstract

Immunity against the pre-erythrocytic stages of malaria is the most promising, as it is strong and fully sterilizing. Yet, the underlying immune effectors against the human Plasmodium falciparum pre-erythrocytic stages remain surprisingly poorly known and have been little explored, which in turn prevents any rational vaccine progress. Evidence that has been gathered in vitro and in vivo, in higher primates and in humans, is reviewed here, emphasizing the significant role of IFN-γ, either as a critical immune mediator or at least as a valuable surrogate marker of protection. One may hope that these results will trigger investigations in volunteers immunized either by optimally irradiated or over-irradiated sporozoites, to quickly delineate better surrogates of protection, which are essential for the development of a successful malaria vaccine.

Reduction of multiplicity of infections but no change in msp2 genetic diversity in Plasmodium falciparum isolates from Congolese children after introduction of artemisinin-combination therapy

“…The study was conducted in Madibou, a semi-urban district located in a Southern part of Brazzaville [16], where malaria transmission is high and perennial with an entomological inoculation rate (EIR) of 22.5 infective bites/person/year estimated several years ago [17,18]. …”

Immunization with Apical Membrane Antigen 1 Confers Sterile Infection-Blocking Immunity against Plasmodium Sporozoite Challenge in a Rodent Model

“…Although there are no established correlates of protective immunity against malaria, protection at the liver stage is thought to be mediated primarily by CD8 ϩ T cells, with a role for CD4 ϩ T cells, and production of Th1-type cytokines (13,67). IFN-␥ is routinely used as surrogate marker for preerythrocytic-stage immunity (72). Studies comparing malariaspecific cytokine profiles of protected and unprotected individuals and their capacity for inhibition of the development of early parasite stages confirmed the importance of IFN-␥ for protection but also established TNF as mediator of inhibition of preerythrocytic development (73)(74)(75)(76)(77)(78).…”

Preliminary Investigations into the Binding Interactions between Plasmodial and Host Proteins using Computational Approaches

“…Vaccine preparation using human P.falciparun Liver Stage Antigen 3 (LSA-3) has demonstrated that Interferon-gamma (IFN-g) provided the protection experienced in the pre-eryhrocyctic stage, suggesting interaction between the LSA-3 peptide and the paratope that produced Interferongamma (IFN-g) [63]. Result shows AMA-1 0.4078 and Inferon gamma, 0.406.…”

“…Clinical experiments have demonstrated that Inferon-gamma inhibit Liver Schizogony of the Plasmodium falciparun [63]. Vaccine preparation using human P.falciparun Liver Stage Antigen 3 (LSA-3) has demonstrated that Interferon-gamma (IFN-g) provided the protection experienced in the pre-eryhrocyctic stage, suggesting interaction between the LSA-3 peptide and the paratope that produced Interferongamma (IFN-g) [63].…”

“…Perforin and Complement Receptor Type 9 are spore-forming proteins of the Plasmodial hosts involved in the disruption of the cell membrane of the viruses and micro-organisms [62], UNIPROT [22]. [63]. Sporozoite entry into the PV is found to have been mediated by least two hepatocyte surface molecules of the host, the tetraspanin CD81 and Scavenger receptor B1 (SRB1) [14,64].…”