Codebase for the microarray preprocessing, QC, normalisation and downstream analysis (DGE, correlation analysis) of the study.
Sterile protection against Plasmodium vivax malaria by repeated blood stage infection in the Aotus monkey model
1,2,3Nicanor Obaldía III*, 3,4Joao Luiz Da Silva Filho, 1Marlon Núñez, 5Katherine A. Glass, 5Tate Oulton, 3,4Fiona Achcar, 6Grennady Wirjanata, 2Manoj Duraisingh, 7Philip Felgner, 5Kevin K.A. Tetteh, 6Zbynek Bozdech, 3Thomas D. Otto, 2,3,4Matthias Marti*
The malaria parasite Plasmodium vivax remains a major global public health challenge, causing major morbidity across tropical and subtropical regions. Several candidate vaccines are in preclinical and clinical trials, however no vaccine against P. vivax malaria is approved for use in humans. Here we assessed whether P. vivax strain-transcendent immunity can be achieved by repeated infection in Aotus monkeys. For this purpose, we repeatedly infected six animals with blood stages of the P. vivax Salvador 1 (SAL-1) strain until sterile immune, and then challenged with the AMRU-1 strain. Sterile immunity was achieved in 4/4 Aotus monkeys after two homologous infections with the SAL-1 strain, while partial protection against a heterologous AMRU-1 challenge (i.e., delay to infection and reduction in peak parasitemia compared to control) was achieved in 3/3 monkeys. IgG levels based on P. vivax lysate ELISA and protein microarray increased with repeated infections and correlated with the level of homologous protection. Analysis of parasite transcriptional profiles across inoculation levels provided no evidence of major antigenic switching upon homologous or heterologous challenge. In contrast, we observed significant transcriptional differences in the P. vivax core gene repertoire between SAL-1 and AMRU-1. Together with the strain-specific genetic diversity between SAL-1 and AMRU-1 these data suggest that the partial protection upon heterologous challenge is due to molecular differences between strains (at genome and transcriptome level) rather than immune evasion by antigenic switching. Our study demonstrates that sterile immunity against P. vivax can be achieved by repeated homologous blood stage infection in Aotus monkeys, thus providing a benchmark to test the efficacy of candidate blood stage P. vivax malaria vaccines.