Proteome-wide analysis of a malaria vaccine study reveals personalized humoral immune profiles in Tanzanian adults.

Flavia Camponovo,Jozelyn V Pablo,B Kim Lee Sim,Xiaowu Liang,Andy A Teng,Joseph J Campo,Christopher Hung,Melissa A Penny,Salim Abdulla,Marcel Tanner,Said Jongo,Stephen L Hoffman,Amit Oberai,Timothy Q Le,Claudia Daubenberger

doi:10.7554/elife.53080

Abstract

Tanzanian adult male volunteers were immunized by direct venous inoculation with radiation-attenuated, aseptic, purified, cryopreserved Plasmodium falciparum (Pf) sporozoites (PfSPZ Vaccine) and protective efficacy assessed by homologous controlled human malaria infection (CHMI). Serum immunoglobulin G (IgG) responses were analyzed longitudinally using a Pf protein microarray covering 91% of the proteome, providing first insights into naturally acquired and PfSPZ Vaccine-induced whole parasite antibody profiles in malaria pre-exposed Africans. Immunoreactivity was identified against 2239 functionally diverse Pf proteins, showing a wide breadth of humoral response. Antibody-based immune 'fingerprints' in these individuals indicated a strong person-specific immune response at baseline, with little changes in the overall humoral immunoreactivity pattern measured after immunization. The moderate increase in immunogenicity following immunization and the extensive and variable breadth of humoral immune response observed in the volunteers at baseline suggest that pre-exposure reduces vaccine-induced antigen reactivity in unanticipated ways.

Highlights

Malaria control and elimination remain a significant public health challenge, and an effective malaria vaccine targeting Plasmodium falciparum (Pf) would be an important tool to accelerate burden reduction, curb the spread of drug resistant strains and facilitate focal Pf malaria elimination (Greenwood, 2008)
92 serum samples from 46 volunteers enrolled in the BSPZV1 study were probed on Pf whole proteome microarrays, including samples collected at baseline and 2 weeks after last immunization (Figure 1)
All volunteers included in the study had no parasitemia at the start of the study (measured by malaria thick blood smears (TBS)) and no parasitemia before controlled human malaria infection (CHMI) (Jongo et al, 2018)

Summary

Introduction

Malaria control and elimination remain a significant public health challenge, and an effective malaria vaccine targeting Plasmodium falciparum (Pf) would be an important tool to accelerate burden reduction, curb the spread of drug resistant strains and facilitate focal Pf malaria elimination (Greenwood, 2008). IgG specific to the Pf circumsporozoite protein (CSP) measured by ELISA or detected against PfSPZ by automated immunofluorescence assay (aIFA) correlated with protection in malaria naıve volunteers at 3 week and 21–25 week post-vaccination homologous CHMI in one study (Ishizuka et al, 2016). Serum samples from malarianaıve individuals infected by radiation-attenuated sporozoites via mosquito bites have been probed with microarrays covering 23% of all Pf proteins, providing insight into humoral immunity induced by both whole sporozoite vaccination and its association with sterile protection following CHMI (Trieu et al, 2011). Serum samples were collected pre-vaccination and 14 days past last vaccination to understand the PfSPZ Vaccine-induced IgG profiles in Tanzanian male adults participating in the BSPZV1 study and potential correlations between humoral immune responses and PfSPZ vaccine induced protection against homologous CHMI (Jongo et al, 2018). This humoral immune pattern remained largely unchanged following the whole organism based PfSPZ immunization, leading to the hypothesis of natural imprinting of humoral immune responses

Results

Discussion

Ethic statement

Study design of the original trial