Differential cellular recognition of antigens during acute Plasmodium falciparum and Plasmodium vivax malaria

Abstract

Background: Plasmodium falciparum and Plasmodium vivax are co-endemic in the Asia-Pacific region. Their capacity to induce and sustain diverse T-cell responses underpins protective immunity. We compared T-cell responses to the largely conserved merozoite surface protein-5 (PfMSP5) during acute and convalescent falciparum and vivax malaria.

Methods: Lymphoproliferation and IFN--γ secretion to PfMSP5 and purified protein derivate were quantified in adults with falciparum (n=34), and vivax malaria (n=12) or asymptomatic residents (n=10) of Papua, Indonesia. Responses were reassessed 7-28 days following treatment.

Results: The frequency of IFN-γ responders to PfMSP5 was similar in acute falciparum (63%) or vivax (67%) malaria. However, significantly more IFN-γ-secreting cells were detectable during vivax compared with falciparum infection. Purified protein derivative responses showed a similarly enhanced pattern. While rapidly lost in vivax patients, PfMSP5-specific responses in falciparum malaria remained to day 28. By contrast, frequency and magnitude of lymphoproliferation to PfMSP5 were similar for falciparum and vivax infections.

Conclusion: Cellular PfMSP5-specific responses are most frequent during either acute falciparum or vivax malaria, indicating functional T-cell responses to conserved antigens. Both effector and central memory T-cell functions are increased. Greater IFN-γ responses in acute P. vivax, suggest enhancement of pre-existing effector T-cells during acute vivax infection.

Figure 1

Longitudinal responses to merozoite surface protein 5. (A) Longitudinal interferon-γ (IFN-γ) responses to merozoite surface protein 5 (MSP5) in samples from patients with acute P. falciparum malaria (Pf, left panel) and acute P. vivax malaria (Pv, right panel). (B) Longitudinal IFN-γ response to MSP5 in paired samples from 3 patients with acute P. falciparummalaria (Pf, left panel) and 4 patients with acute P. vivax malaria (Pv, right panel). All graphs show number of spot forming units (SFU) per million PBMC with background SFU subtracted. Horizontal lines depict the median. (C) Longitudinal proliferation response to PfMSP5 in cross-sectional samples from patients with acute P. falciparum malaria (Pf, left panel) and acute P. vivax malaria (Pv, right panel). Positive response defined as stimulation index (SI) > 2. Horizontal lines depict the median. Dashed lines represent cut-off value for positive response (SI = 2).

Figure 2

Reactivity pattern to P. falciparum merozoite surface protein 5 and P. vivax merozoite surface protein 5. Eleven patients with falciparum malaria (Pf),7 with vivax malaria (Pv) and 10 asymptomatic individuals (AC) were tested for IFN-gamma and proliferation responses to PfMSP5 and PvMSP5. Positive responses are shown as black squares. ND, not determined.