Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination.

Scientific Reports
Jason A BaileyChristopher V Plowe

Abstract

Vaccines based on Plasmodium falciparum apical membrane antigen 1 (AMA1) have failed due to extensive polymorphism in AMA1. To assess the strain-specificity of antibody responses to malaria infection and AMA1 vaccination, we designed protein and peptide microarrays representing hundreds of unique AMA1 variants. Following clinical malaria episodes, children had short-lived, sequence-independent increases in average whole-protein seroreactivity, as well as strain-specific responses to peptides representing diverse epitopes. Vaccination resulted in dramatically increased seroreactivity to all 263 AMA1 whole-protein variants. High-density peptide analysis revealed that vaccinated children had increases in seroreactivity to four distinct epitopes that exceeded responses to natural infection. A single amino acid change was critical to seroreactivity to peptides in a region of AMA1 associated with strain-specific vaccine efficacy. Antibody measurements using whole antigens may be biased towards conserved, immunodominant epitopes. Peptide microarrays may help to identify immunogenic epitopes, define correlates of vaccine protection, and measure strain-specific vaccine-induced antibodies.

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Citations

Jan 26, 2021·Frontiers in Cellular and Infection Microbiology·Fang HuangChristopher V Plowe
Mar 12, 2021·Bioinformatics·Zihao ZhengMichael A Newton
Apr 3, 2021·Frontiers in Cellular and Infection Microbiology·Ana Caroline Barbosa FrançaIrene S Soares
Apr 10, 2021·Nature Reviews. Genetics·Daniel E NeafseyBronwyn L MacInnis

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Methods Mentioned

BETA
peptide array
protein array
PCR
ELISA

Software Mentioned

Sequencher
R Project for Statistical Computing
R Bioconductor
stats

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