scholarly journals Diverse outcomes of controlled human malaria infection originate from host-intrinsic immune variation and not var gene switching

2020 ◽  
Author(s):  
Kathryn Milne ◽  
Alasdair Ivens ◽  
Adam J. Reid ◽  
Magda E. Lotkowska ◽  
Áine O'Toole ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Severe Disease ◽  
Myeloid Cell ◽  
Current Theory ◽  
Human Malaria ◽  
Relative Contribution ◽  
Gene Profiles ◽  
Controlled Human Malaria Infection ◽  
Gene Switching ◽  
Selection Of

Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the response of naive hosts to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease preferentially expand in naive hosts (as predicted by current theory) we found that var gene profiles were unchanged after 10-days of infection. The diverse outcomes of CHMI therefore depend upon human immune variation and there is no evidence for switching or selection of var genes in naive hosts.

scholarly journals Mapping immune variation and var gene switching in naive hosts infected with Plasmodium falciparum

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kathryn Milne ◽  
Alasdair Ivens ◽  
Adam J Reid ◽  
Magda E Lotkowska ◽  
Aine O'Toole ◽  
...  
Keyword(s):  
Host Response ◽  
Severe Disease ◽  
Myeloid Cell ◽  
Relative Contribution ◽  
Variant Surface Antigen ◽  
Controlled Human Malaria Infection ◽  
Cell Suppression ◽  
Induced Changes ◽  
Gene Switching ◽  
Var Gene

Falciparum malaria is clinically heterogeneous and the relative contribution of parasite and host in shaping disease severity remains unclear. We explored the interaction between inflammation and parasite variant surface antigen (VSA) expression, asking whether this relationship underpins the variation observed in controlled human malaria infection (CHMI). We uncovered marked heterogeneity in the host response to blood challenge; some volunteers remained quiescent, others triggered interferon-stimulated inflammation and some showed transcriptional evidence of myeloid cell suppression. Significantly, only inflammatory volunteers experienced hallmark symptoms of malaria. When we tracked temporal changes in parasite VSA expression to ask whether variants associated with severe disease rapidly expand in naive hosts, we found no transcriptional evidence to support this hypothesis. These data indicate that parasite variants that dominate severe malaria do not have an intrinsic growth or survival advantage; instead, they presumably rely upon infection-induced changes in their within-host environment for selection.

scholarly journals Immunoprofiles associated with controlled human malaria infection and naturally acquired immunity identify a shared IgA pre-erythrocytic immunoproteome

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Andrea A. Berry ◽  
Joshua M. Obiero ◽  
Mark A. Travassos ◽  
Amed Ouattara ◽  
Drissa Coulibaly ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Vaccine Development ◽  
Protein Microarray ◽  
Antibody Responses ◽  
Liver Stage ◽  
Human Malaria ◽  
Controlled Human Malaria Infection ◽  
Iga Antibody ◽  
Potential Vaccine ◽  
Antigen Protein

AbstractKnowledge of the Plasmodium falciparum antigens that comprise the human liver stage immunoproteome is important for pre-erythrocytic vaccine development, but, compared with the erythrocytic stage immunoproteome, more challenging to classify. Previous studies of P. falciparum antibody responses report IgG and rarely IgA responses. We assessed IgG and IgA antibody responses in adult sera collected during two controlled human malaria infection (CHMI) studies in malaria-naïve volunteers and in 1- to 6-year-old malaria-exposed Malian children on a 251 P. falciparum antigen protein microarray. IgG profiles in the two CHMI groups were equivalent and differed from Malian children. IgA profiles were robust in the CHMI groups and a subset of Malian children. We describe immunoproteome differences in naïve vs. exposed individuals and report pre-erythrocytic proteins recognized by the immune system. IgA responses detected in this study expand the list of pre-erythrocytic antigens for further characterization as potential vaccine candidates.

scholarly journals Outcomes of controlled human malaria infection after BCG vaccination

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jona Walk ◽  
L. Charlotte J. de Bree ◽  
Wouter Graumans ◽  
Rianne Stoter ◽  
Geert-Jan van Gemert ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Human Malaria ◽  
Bcg Vaccination ◽  
Controlled Human Malaria Infection

scholarly journals Mosquito Bite-Induced Controlled Human Malaria Infection withPlasmodium vivaxorP. falciparumGenerates Immune Responses to Homologous and Heterologous Preerythrocytic and Erythrocytic Antigens

2018 ◽  
Vol 87 (3) ◽  
Author(s):  
Cysha E. Hall ◽  
Lisa M. Hagan ◽  
Elke Bergmann-Leitner ◽  
Donna M. Tosh ◽  
Jason W. Bennett ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Similar Proportion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Content Type ◽  
Human Malaria ◽  
Before And After ◽  
Controlled Human Malaria Infection

ABSTRACTSeroepidemiological studies on the prevalence of antibodies to malaria antigens are primarily conducted on individuals from regions of endemicity. It is therefore difficult to accurately correlate the antibody responses to the timing and number of prior malaria infections. This study was undertaken to assess the evolution of antibodies to the dominant surface antigens ofPlasmodium vivaxandP. falciparumfollowing controlled human malaria infection (CHMI) in malaria-naive individuals. Serum samples from malaria-naive adults, collected before and after CHMI with eitherP. vivax(n= 18) orP. falciparum(n= 18), were tested for the presence of antibodies to the circumsporozoite protein (CSP) and the 42-kDa fragment of merozoite surface protein 1 (MSP-142) ofP. vivaxandP. falciparumusing an enzyme-linked immunosorbent assay (ELISA). Approximately 1 month following CHMI with eitherP. vivaxorP. falciparum, >60% of subjects seroconverted to homologous CSP and MSP-1. More than 50% of the subjects demonstrated reactivity to heterologous CSP and MSP-142, and a similar proportion of subjects remained seropositive to homologous MSP-142>5 months after CHMI. Computational analysis provides insight into the presence of cross-reactive responses. The presence of long-lived and heterologous reactivity and its functional significance, if any, need to be taken into account while evaluating malaria exposure in field settings.

scholarly journals Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection

2016 ◽  
Vol 7 ◽  
Author(s):  
Susanne H. Hodgson ◽  
David Llewellyn ◽  
Sarah E. Silk ◽  
Kathryn H. Milne ◽  
Sean C. Elias ◽  
...  
Keyword(s):  
Malaria Infection ◽  
Human Malaria ◽  
Controlled Human Malaria Infection
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