Does malaria suffer from lack of memory?

Abstract

It is widely perceived that immunity to malaria is, to an extent, defective and that one component of this defective immune response is the inability to induce or maintain long-term memory responses. If true, this is likely to pose problems for development of an effective vaccine against malaria. In this article, we critically review and challenge this interpretation of the epidemiological and experimental evidence. While evasion and modulation of host immune responses clearly occurs and naturally acquired immunity is far from optimal, mechanisms to control blood-stage parasites are acquired and maintained by individuals living in endemic areas, allowing parasite density to be kept below the threshold for induction of acute disease. Furthermore, protective immunity to severe pathology is achieved relatively rapidly and is maintained in the absence of boosting by re-infection. Nevertheless, there are significant challenges to overcome. The need for multiple infections to acquire immunity means that young children remain at risk of infection for far too long. Persistent or frequent exposure to antigen seems to be required to maintain anti-parasite immunity (premunition). Lastly, pre-erythrocytic and sexual stages of the life cycle are poorly immunogenic, and there is little evidence of effective pre-erythrocytic or transmission-blocking immunity at the population level. While these problems might theoretically be due to defective immunological memory, we suggest alternative explanations. Moreover, we question the extent to which these problems are malaria-specific rather than generic (i.e. result from inherent limitations of the vertebrate immune system).

Multiple functions of human T cells generated by experimental malaria challenge

“…Indeed, in one particular study volunteers were immunized with low doses of Plasmodium-infected RBC (iRBC), and they produced T-cell IFN-g responses against blood-stage Ag that were associated with protection from challenge in the absence of Ab responses [7]. A frequently described observation is the apparently short-lived immunity generated after exposure to the parasite [8,9], which may be a result of depressed cellular immunity [10,11]. We have recently shown that recipients of experimental malaria vaccines in Kenya had decreased T-cell responses against the vaccine Ag when parasitemic at the time of vaccination [12].…”

Development of Memory CD8+ T Cells and Their Recall Responses during Blood-Stage Infection with Plasmodium berghei ANKA

“…Anecdotal evidence suggests rapid loss of malarial immunity when people leave endemic areas followed by risk of developing symptomatic malaria upon later revisits to the endemic area (8). However, experimental evidence for the generation and maintenance of malaria immunological memory is relatively scarce (9). Several mechanisms have been proposed to explain the poor generation and maintenance of memory immune responses in malaria.…”

Malaria vaccines 1985–2005: a full circle?

“…However, the latter, which is directed primarily against asexual blood stages, requires repeated exposure and involves persistence of infection, responses to complex antigenic polymorphisms, immune modulation and immune evasion. On that basis, it has been argued that, to be effective, a vaccine should not induce a sterilizing immunity, certainly against the clinically important phase of infection [47]. The goal for pre-erythrocytic (and transmission-blocking) vaccines remains the prevention of all parasite development, but this is far from being achieved at present.…”