Major Histocompatibility Complex and Malaria: Focus on Plasmodium vivax Infection

Abstract

The importance of host and parasite genetic factors in malaria resistance or susceptibility has been investigated since the middle of the last century. Nowadays, of all diseases that affect man, malaria still plays one of the highest levels of selective pressure on human genome. Susceptibility to malaria depends on exposure profile, epidemiological characteristics, and several components of the innate and adaptive immune system that influences the quality of the immune response generated during the Plasmodium lifecycle in the vertebrate host. But it is well known that the parasite’s enormous capacity of genetic variation in conjunction with the host genetics polymorphism is also associated with a wide spectrum of susceptibility degrees to complicated or severe forms of the disease. In this scenario, variations in genes of the major histocompatibility complex (MHC) associated with host resistance or susceptibility to malaria have been identified and used as markers in host–pathogen interaction studies, mainly those evaluating the impact on the immune response, acquisition of resistance, or increased susceptibility to infection or vulnerability to disease. However, due to the intense selective pressure, number of cases, and mortality rates, the majority of the reported associations reported concerned Plasmodium falciparum malaria. Studies on the MHC polymorphism and its association with Plasmodium vivax, which is the most widespread Plasmodium and the most prevalent species outside the African continent, are less frequent but equally important. Despite punctual contributions, there are accumulated evidences of human genetic control in P. vivax infection and disease. Herein, we review the current knowledge in the field of MHC and derived molecules (HLA Class I, Class II, TNF-α, LTA, BAT1, and CTL4) regarding P. vivax malaria. We discuss particularly the results of P. vivax studies on HLA class I and II polymorphisms in relation to host susceptibility, naturally acquired immune response against specific antigens and the implication of this knowledge to overcome the parasite immune evasion. Finally, the potential impact of such polymorphisms on the development of vaccine candidate antigens against P. vivax will be studied.

Synthetic Antigens Derived from Plasmodium falciparum Sporozoite, Liver, and Blood Stages: Naturally Acquired Immune Response and Human Leukocyte Antigen Associations in Individuals Living in a Brazilian Endemic Area

“…Therefore, HLA allelic forms can influence the host capacity to mount both a naturally acquired and an artificially induced antiplasmodial humoral immune response. 18,19,[81][82][83][84][85][86][87][88][89] In view of these data, we hypothesized the possible involvement of HLA class II molecules in the modulation of the antibody specificity profiles induced by P. falciparum antigens in the exposed group. In our study, the analysis of the presence of the HLA-DRB1* and HLA-DQB1* allelic groups and the antibody response to CSP, LSA-1, and MSP-3 did not show any association.…”

What Is Known about the Immune Response Induced by Plasmodium vivax Malaria Vaccine Candidates?

“…Immune response during the erythrocyte stage is mainly mediated by antibodies while a cellular response predominates during the hepatic stage ( 56 ). CD4+ T-, B-, and NK cells also play an important role in the immune response induced by the parasite during the erythrocyte stage since immunity depends on memory B-cell production and lifespan, following infection ( 57 ).…”

Whole Genome Sequencing of Plasmodium vivax Isolates Reveals Frequent Sequence and Structural Polymorphisms in Erythrocyte Binding Genes

“…Previous studies have shown high levels of genetic diversity among P. vivax isolates in endemic countries [16, 100, 101]. Such a diversity was directly related to high transmission intensity and/or frequent gene exchange between parasite populations via human movement [4, 12, 13, 53]. For example, previous studies using microsatellites have demonstrated a consistently high level of intra-population diversity ( H E = 0.83) but low between-population differentiation ( F ST ranged from 0.001-0.1] in broader regions of Ethiopia [53, 99].…”