Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination
MetadataShow full item record
AbstractVaccines 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. Copyright 2020, The Author(s).
SponsorsHoward Hughes Medical Institute, HHMI; National Institutes of Health, NIH: U01AI065683, R01HL130750, U19AI129386, R01AI093635, K23AI125720, T32AI007524, R21AI119733
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85080920956&doi=10.1038%2fs41598-020-60551-z&partnerID=40&md5=5f88f46110c2b22b97899b904d3d49d1; http://hdl.handle.net/10713/12232
- Immunoglobulin G subclass and antibody avidity responses in Malian children immunized with Plasmodium falciparum apical membrane antigen 1 vaccine candidate FMP2.1/AS02(A).
- Authors: Berry AA, Gottlieb ER, Kouriba B, Diarra I, Thera MA, Dutta S, Coulibaly D, Ouattara A, Niangaly A, Kone AK, Traore K, Tolo Y, Mishcherkin V, Soisson L, Diggs CL, Blackwelder WC, Laurens MB, Sztein MB, Doumbo OK, Plowe CV, Lyke KE
- Issue date: 2019 Jan 18
- Identification of adjuvants for clinical trials performed with Plasmodium falciparum AMA1 in rabbits.
- Authors: Younis S, Faber BW, Kocken CHM, Remarque EJ
- Issue date: 2019 Jul 30
- Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.
- Authors: Sirima SB, Durier C, Kara L, Houard S, Gansane A, Loulergue P, Bahuaud M, Benhamouda N, Nebié I, Faber B, Remarque E, Launay O, AMA1-DiCo Study Group
- Issue date: 2017 Oct 27
- Limited antigenic diversity of Plasmodium falciparum apical membrane antigen 1 supports the development of effective multi-allele vaccines.
- Authors: Terheggen U, Drew DR, Hodder AN, Cross NJ, Mugyenyi CK, Barry AE, Anders RF, Dutta S, Osier FH, Elliott SR, Senn N, Stanisic DI, Marsh K, Siba PM, Mueller I, Richards JS, Beeson JG
- Issue date: 2014 Oct 16
- Defining the antigenic diversity of Plasmodium falciparum apical membrane antigen 1 and the requirements for a multi-allele vaccine against malaria.
- Authors: Drew DR, Hodder AN, Wilson DW, Foley M, Mueller I, Siba PM, Dent AE, Cowman AF, Beeson JG
- Issue date: 2012