Chapter Three - Natural Acquisition of Immunity to Plasmodium vivax: Epidemiological Observations and Potential Targets
Section snippets
Overview of Naturally Acquired Immunity to Malaria
A major controlling force that determines the incidence and prevalence of malaria infection and disease in endemic areas is the parasitological and clinical immunity collectively referred to as naturally acquired immunity (NAI). Generally, NAI determines not only the age-specific incidence and prevalence of P. falciparum (Pf膘) and P. vivax (Pv) infections but also the expression of pathological processes that underlie the clinical manifestations of infection. Improved understanding of the
Differential Acquisition of Immunity to P. vivax and P. falciparum Under Natural Exposure
In the New Guinea island, which is highly endemic for both P. falciparum and P. vivax (Muller et al., 2003), P. vivax is the predominate source of malarial infections and disease in children younger than 2 years (Senn et al., 2012). The incidence of P. vivax malaria started to rapidly decrease from the second year of life, whereas P. falciparum incidence continued to increase until the fourth year in observational cohort studies in children aged 1–4 (Lin et al., 2010) and 5–14 years (Michon
Acquisition of Immunity in Experimental Infections – Lessons from Malaria Therapy Patients and Irradiated Sporozoites
Prior to the confirmation in 1947 that penicillin could cure syphilis, the primary treatment for neurosyphilis was fevers induced with malarial infections. Plasmodium vivax was the preferred treatment over P. falciparum because it could produce sustained fevers without requiring treatment. Because malaria therapy did not cure syphilis, but just delayed the progression of disease, individuals were often repeatedly infected. With support from the Rockefeller Foundation in the 1930s and early
Unique Biological Characteristics of P. vivax that Contribute to NAI
Individuals exposed to a comparable number of infections and clinical episodes of P. vivax and P. falciparum acquire clinical immunity to P. vivax more rapidly than P. falciparum (Lin et al., 2010; Maitland et al., 1996; Michon et al., 2007). Pv has several important differences in its biology compared to Pf, which may help to explain the differences in the acquisition of immunity to each of these species.
Effector Mechanisms for Blood-Stage Immunity
Adoptive transfer of serum from avian (Manwell and Goldstein, 1940), murine (Parashar et al., 1977), non-human primate (Coggeshall and Kumm, 1937) and human falciparum malarias with NAI (Cohen et al., 1961; McGregor, 1964) into naïve animals or humans protects against clinical malaria or significantly attenuates the severity and burden of malaria (Cohen et al., 1961; McGregor, 1964). Such experiments have established that Abs are critical for NAI to blood-stage malarial infection.
Targets of Blood-Stage Immunity
Although much can be inferred from the basic biology of Plasmodium merozoites (Fig. 3.2), there are many gaps in our knowledge of the biology of P. vivax merozoites. For example, why they selective invade host reticulocytes and details of the growth and development of the various blood-stage developmental forms (reviewed in Galinski et al., 2005). In addition, only a relatively small group of merozoite proteins have so far been identified with specific localisations and confirmed functional
Immune Responses to Malaria Pre-Erythrocytic Stages
In humans, malarial infection is initiated by the bite of an infected Anopheles mosquito that injects sporozoites into the host’s bloodstream. Although mosquitoes from highly endemic areas are estimated to carry up to 104 sporozoites in their salivary glands, it has been calculated that during a blood meal an infected mosquito inoculates a median number of only 15 parasites into the host (Rosenberg et al., 1990).
After inoculation, the sporozoites move through dermal cells and enter into the
Sexual Stage Parasites and Transmission-Blocking Immunity
The target stages of the TBI are the sexual stages of the Plasmodium life cycle. The sexual stage is initiated in the vertebrate host bloodstream as male and female gametocytes. After the ingestion of the infected blood by Anopheles mosquito, male and female gametes emerge and fertilise to form zygotes in the mosquito midgut. The zygotes transform into motile ookinetes, which traverse the epithelium of the mosquito midgut to further develop into oocysts (Tsuboi et al., 2003).
TBI has initially
Conclusions
Although we have only just begun to understand some of the major processes involved in NAI to P. vivax, the results to date support the premise that developing a multistage P. vivax vaccine may be feasible and is worth pursuing. The more rapid development of NAI to P. vivax even indicates that a highly efficacious P. vivax vaccine may be easier to achieve that a vaccine to P. falciparum. This might be especially true if there are fewer redundant pathways for erythrocyte invasion. A
Future Directions
- 1.
Compare Ab responses from putatively immune and susceptible individuals using protein arrays representing Pv blood-stage antigens in longitudinal cohort studies with the aim to identify new targets of blood-stage immune responses.
- 2.
Better characterize surface-expressed proteins on Pv-IEs and relate how these proteins are involved in stimulating NAI, and, potentially, immune evasion strategies.
- 3.
Study the role of host cellular immunity and protection against blood-stage Pv infection, including the
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2023, The LancetPlasmodium vivax – How hidden reservoirs hinder global malaria elimination
2022, Parasitology InternationalCitation Excerpt :These are briefly outlined below and highlight that the elimination of P. vivax will require vivax-specific tools and tailored approaches. Naturally acquired immunity against P. vivax develops rapidly at a younger age than that observed for P. falciparum, making young children the main risk group for severe vivax malaria in highly endemic settings [28]. The incidence of P. vivax malaria in children in PNG aged 1–4 years decreases rapidly after the age of 2, with most children acquiring immunity to clinical P. vivax by the age of 5 [29,30].
Hypnozoite dynamics for Plasmodium vivax malaria: The epidemiological effects of radical cure
2022, Journal of Theoretical BiologyCitation Excerpt :In the absence of strain structure, our model can be extended to capture the acquisition and decay of blood-stage immunity, with observational models mapping the immunity level to the probability of clinical infection and parasite density distributions (see Appendix C.3 for details); coupling host and vector dynamics, whilst accounting for the acquisition of transmission-blocking immunity through a similar construction, is the subject of current work. However, since antimalarial immunity is strain-specific, albeit with cross-protectivity amongst strains (Mueller et al., 2013), strain structure is another important consideration; repeated exposure to a single strain, either through the activation of homologous hypnozoites or across multiple bites, can generate strong strain-specific immune protection, but partial protection against heterologous strains (Mueller et al., 2013), thereby modulating blood-stage dynamics. Modelling strain structure would also allow for precise distributions of MOI (here, we assume MOI to be given by the number of active infections at a given point in time, without accounting for the possibility of overlapping strains across infections, nor polyclonal primary infections).
Analysis of Apical Membrane Antigen (AMA)-1 characteristics using bioinformatics tools in order to vaccine design against Plasmodium vivax
2019, Infection, Genetics and EvolutionCitation Excerpt :The best accuracy and sensitivity are for consensus and combined prediction approaches respectively, which are significantly higher compared to the individual methods (ANN and SVM). P. vivax is an intracellular parasite infecting erythrocytes and hepatocytes, therefore; T-cell mediated cellular immunity plays a critical role against the infection (Mueller et al., 2013). Designing a protective vaccine against P. vivax is still a significant need.
Mathematical models of Plasmodium vivax transmission: A scoping review
2024, PLoS Computational Biology