What is the current understanding of the mechanisms behind naturally acquired immunity to malaria

What is the current understanding of the mechanisms behind naturally acquired immunity to malaria?
In sub-Saharan Africa alone, malaria is one of the main causes of mortality, accounting for over 390 thousand deaths in 2016 (Md Idris, 2017). If the mechanisms of naturally acquired immunity (NAI) can be understood, the prospect of a vaccine would be less ambitious than originally thought; once developed, thousands of lives could be saved. There are four human-infecting malaria species, this review will be focusing on naturally acquired immunity to Plasmodium falciparum, the most common species in sub-Saharan Africa.
The basic principle of vaccination is exposure to modified pathogens that may cause harm. Supporting this claim, antibody levels have been found to generally increase with age and exposure (Pinkevych, 2012). NAI tends to only arise when exposed to regular infection of Plasmodium falciparum from birth. Many factors, however, influence the rate at which it’s acquired, such as pregnancy, age and intensity of malaria transmission. (Guinovart, 2012)
Infants are rarely immune to malaria. Research suggests antibody responses increases with age. The (Pinkevych, 2012) study reported antibody prevalence rapidly rose in children ages 6-10 years; more than 75% of participants in this study became seropositive by 20 years of age(Pinkevych, 2012). Immunity is weak in children under the age of five, suggesting their immune responses are less stable, possibly because the immune system is still developing (Pinkevych, 2012). Interestingly it was observed that exposure to erythrocytic-stage antigens of Plasmodium falciparum during the first months of life didn’t contribute to the development of NAI, although exposure to the parasite during the second half of infancy is a crucial acquisition of NAI (Guinovart, 2012). It’s understandable infants don’t obtain immunity straight away, they haven’t had sufficient time to have had multiple infections.
In contrast to the previous paragraph, Immunity is non-age specific. Data suggests that contact with the parasite is needed at some point during infancy to envelop NAI, but the timing of the exposure isn’t a major contributing factor. The study concluded that young infants with relatively immature immune systems and low exposure were able to build NAIs as well as older infants (Guinovart, 2012). These infants don’t acquire a full immunity, it’s only developing at this point. Further research is required to quantify how many infections are needed within a time period to obtain adequate immunity.
There are also different types of immunity, potentially even strain-specific. Liver stage immunity acts to block infected bites reaching the blood stage (Md Idris, 2017). Whereas strain-specific immunity acquires as a result of being infected with a certain strain, which is the neutralised, causing immunity to that strain only. General immunity can be acquired when any strain of parasite is able to be neutralised. The most important antigens in this case are AMA-1 and MSP-1 which are produced continuously, despite the parasite going through several cycles of multiplication(Md Idris, 2017).
The literature forming this review conclude that for natural immunity to be acquired, repetitive exposure to Plasmodium falciparum is essential. A limitation of these studies is that Plasmodium falciparum has several growth stages, where it changes form every time. This makes it difficult to track the stages of infection, as well as record the level of immunity that has been acquired. Regarding the future, further research is required; more advanced techniques are needed to be able to isolate and analyse the parasite at each of its growth phases.