Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial

Tchum, Samuel Kofi; Sakyi, Samuel Asamoah; Adu, Bright; Arthur, Fareed K. N.; Oppong, Felix Boakye; Dzabeng, Francis; Amoani, Benjamin; Thomas, GN; Poku-Asante, Kwaku

doi:10.1371/journal.pone.0253544

Cited by 3 publications

(7 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the attenuated immune response, in particular the impaired GC response, indicates that iron deficiency could counteract the formation of efficient immune memory to subsequent malaria infections. This is in line with human observational studies that have found a link between iron deficiency and weak antibody responses to P. falciparum (7,45,46). In humans, anti-parasite immunity forms very slowly and only after numerous repeated exposures to malaria infection (2).…”

Section: Discussionsupporting

confidence: 90%

See 1 more Smart Citation

Cellular iron governs the host response to malaria

Wideman

Frost

Richter³

et al. 2023

Preprint

View full text Add to dashboard Cite

Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor (TfrcY20H/Y20H), which limits the ability of cells to internalise iron from plasma. At homeostasisTfrcY20H/Y20Hmice appear healthy and are not anaemic. However,TfrcY20H/Y20Hmice infected withPlasmodium chabaudi chabaudiAS showed significantly higher peak parasitaemia and body weight loss. We found thatTfrcY20H/Y20Hmice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead,P. chabaudiinfectedTfrcY20H/Y20Hmice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production. Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, as ex vivo iron supplementation fully recovered CD4 T cell and B cell function. Despite the inhibited immune response and increased parasitaemia,TfrcY20H/Y20Hmice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria.

show abstract

Section: Discussionsupporting

confidence: 90%

“…In particular, the effects of iron deficiency aside from anaemia, have scarcely been explored. Moreover, any effects on malaria immunity have not been investigated beyond a few observational studies that found associations between iron deficiency and attenuated antibody responses to malaria in children (7,45,46).…”

Section: Introductionmentioning

confidence: 99%

Cellular iron governs the host response to malaria

Wideman

Frost

Richter³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…On the other hand, asymptomatic Pf infected children living in both low and high transmission settings, showed significantly higher IgG1 antibody response specific to MSP3 than the response specific to UB05 (p<0.0001) [34]. In contrast, IgG3 antibody specific responses to UB05 was higher in both areas.…”

Section: Discussionmentioning

confidence: 84%

Profiles of Immunoglobulin G Antibody Subclass Responses Specific to MSP3 and UB05 in Plasma of Malaria Negative Children Living in Two Different Agro-ecological Settings of Cameroon

Nchinda

2024

JCIM

View full text Add to dashboard Cite

Introduction: In malaria endemic areas, antibody specific to promising asexual blood stage malaria vaccine candidates have been demonstrated to play a critical role in protection during sub-clinical malaria. In this context naturally acquired protective immunity is usually driven by blood stage antigen specific IgG antibody subclass responses among which the cytophilic antibody subclasses IgG1 and IgG3 remain the most relevant. Thus, we have assessed IgG antibody subclass responses specific to Plasmodium spp. derived MSP3 and UB05 malaria vaccine candidates, in plasma of children living in areas differing in malaria transmission intensity within Cameroon. Methods: Using MSP3 and UB05 displayed upon the surface of recombinant RNA coliphage Qβ as previously described in our group, IgG antibody subclass responses specific to both immunogens were profiled in plasma from both P. falciparum (Pf) infected and uninfected malaria asymptomatic children. Results: In malaria negative children living in low transmission areas the cytophilic antibody subclasses IgG1 and IgG3 specific to UB05 were significantly higher (P<0.0001) than those specific to MSP3. In contrast IgG1 and IgG3 antibody subclass responses specific to MSP3 were instead significantly higher (P<0.0001 for IgG1; P=0.0007 for IgG3) in their counterparts living in high malaria transmission settings. In asymptomatic Pf infected children living in both areas, whereas IgG1 antibody subclass responses specific to MSP3 was significantly higher (P<0.0001) than the responses specific to UB05, IgG3 antibody subclass responses specific to UB05 was significantly higher (P<0.0001). Conclusion: Thus, there is a differential generation of cytophilic antibody subclasses specific (IgG1 and IgG3) to two classical asexual blood stage antigens in children living within these areas in a malaria endemic region. Whereas for Pf negative children living in low malaria transmission areas UBO5 specific IgG1 and IgG3 correlated best with naturally acquired immunity against malaria; elevated MSP3 targeted cytophilic antibodies were instead prominent in high malaria transmission areas. Thus, repeated exposure to malaria as it is the case with bimodal as against monomodal rainfall areas might be necessary for sustaining high levels of MSP3 specific cytophilic antibodies. This probably tags MSP3 as an unsuitable candidate to measure correlates of protective immunity against malaria.

show abstract

“…This is in line with human observational studies that have found a link between iron deficiency and weak antibody responses to P . falciparum [ 7 , 44 , 45 ]. In humans, anti-parasite immunity forms very slowly and only after numerous repeated exposures to malaria infection [ 2 ].…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cellular iron governs the host response to malaria

Wideman,

Frost,

Richter

et al. 2023

PLoS Pathog

View full text Add to dashboard Cite

Malaria and iron deficiency are major global health problems with extensive epidemiological overlap. Iron deficiency-induced anaemia can protect the host from malaria by limiting parasite growth. On the other hand, iron deficiency can significantly disrupt immune cell function. However, the impact of host cell iron scarcity beyond anaemia remains elusive in malaria. To address this, we employed a transgenic mouse model carrying a mutation in the transferrin receptor (TfrcY20H/Y20H), which limits the ability of cells to internalise iron from plasma. At homeostasis TfrcY20H/Y20H mice appear healthy and are not anaemic. However, TfrcY20H/Y20H mice infected with Plasmodium chabaudi chabaudi AS showed significantly higher peak parasitaemia and body weight loss. We found that TfrcY20H/Y20H mice displayed a similar trajectory of malaria-induced anaemia as wild-type mice, and elevated circulating iron did not increase peak parasitaemia. Instead, P. chabaudi infected TfrcY20H/Y20H mice had an impaired innate and adaptive immune response, marked by decreased cell proliferation and cytokine production. Moreover, we demonstrated that these immune cell impairments were cell-intrinsic, as ex vivo iron supplementation fully recovered CD4+ T cell and B cell function. Despite the inhibited immune response and increased parasitaemia, TfrcY20H/Y20H mice displayed mitigated liver damage, characterised by decreased parasite sequestration in the liver and an attenuated hepatic immune response. Together, these results show that host cell iron scarcity inhibits the immune response but prevents excessive hepatic tissue damage during malaria infection. These divergent effects shed light on the role of iron in the complex balance between protection and pathology in malaria.

show abstract

Impact of IgG response to malaria-specific antigens and immunity against malaria in pre-school children in Ghana. A cluster randomized, placebo-controlled trial

Cited by 3 publications

References 38 publications

Cellular iron governs the host response to malaria

Cellular iron governs the host response to malaria

Profiles of Immunoglobulin G Antibody Subclass Responses Specific to MSP3 and UB05 in Plasma of Malaria Negative Children Living in Two Different Agro-ecological Settings of Cameroon

Cellular iron governs the host response to malaria

Contact Info

Product

Resources

About