Synergistic malaria vaccine combinations identified by systematic antigen screening

Leyla Y. Bustamante, Gareth T. Powell, Yen Chun Lin, Michael D. Macklin, Nadia Cross, Alison Kemp, Paula Cawkill, Theo Sanderson, Cecile Crosnier, Nicole Muller-Sienerth, Ogobara K. Doumbo, Boubacar Traore, Peter D. Crompton, Pietro Cicuta, Tuan  Tran, Gavin J. Wright, Julian C. Rayner

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.

Original languageEnglish (US)
Pages (from-to)12045-12050
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number45
DOIs
StatePublished - Nov 7 2017

Fingerprint

Malaria Vaccines
Malaria
Antigens
Vaccines
Parasites
Video Microscopy
Weapons
Fever
Erythrocytes
Genome
Antibodies
Population

Keywords

  • Antigen combinations
  • Erythrocyte invasion
  • Malaria
  • Plasmodium falciparum
  • Vaccine

ASJC Scopus subject areas

  • General

Cite this

Bustamante, L. Y., Powell, G. T., Lin, Y. C., Macklin, M. D., Cross, N., Kemp, A., ... Rayner, J. C. (2017). Synergistic malaria vaccine combinations identified by systematic antigen screening. Proceedings of the National Academy of Sciences of the United States of America, 114(45), 12045-12050. https://doi.org/10.1073/pnas.1702944114

Synergistic malaria vaccine combinations identified by systematic antigen screening. / Bustamante, Leyla Y.; Powell, Gareth T.; Lin, Yen Chun; Macklin, Michael D.; Cross, Nadia; Kemp, Alison; Cawkill, Paula; Sanderson, Theo; Crosnier, Cecile; Muller-Sienerth, Nicole; Doumbo, Ogobara K.; Traore, Boubacar; Crompton, Peter D.; Cicuta, Pietro; Tran, Tuan ; Wright, Gavin J.; Rayner, Julian C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 45, 07.11.2017, p. 12045-12050.

Research output: Contribution to journalArticle

Bustamante, LY, Powell, GT, Lin, YC, Macklin, MD, Cross, N, Kemp, A, Cawkill, P, Sanderson, T, Crosnier, C, Muller-Sienerth, N, Doumbo, OK, Traore, B, Crompton, PD, Cicuta, P, Tran, T, Wright, GJ & Rayner, JC 2017, 'Synergistic malaria vaccine combinations identified by systematic antigen screening', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 45, pp. 12045-12050. https://doi.org/10.1073/pnas.1702944114
Bustamante, Leyla Y. ; Powell, Gareth T. ; Lin, Yen Chun ; Macklin, Michael D. ; Cross, Nadia ; Kemp, Alison ; Cawkill, Paula ; Sanderson, Theo ; Crosnier, Cecile ; Muller-Sienerth, Nicole ; Doumbo, Ogobara K. ; Traore, Boubacar ; Crompton, Peter D. ; Cicuta, Pietro ; Tran, Tuan  ; Wright, Gavin J. ; Rayner, Julian C. / Synergistic malaria vaccine combinations identified by systematic antigen screening. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 45. pp. 12045-12050.
@article{0a7bf55a142c4f06adf12827e03831d6,
title = "Synergistic malaria vaccine combinations identified by systematic antigen screening",
abstract = "A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.",
keywords = "Antigen combinations, Erythrocyte invasion, Malaria, Plasmodium falciparum, Vaccine",
author = "Bustamante, {Leyla Y.} and Powell, {Gareth T.} and Lin, {Yen Chun} and Macklin, {Michael D.} and Nadia Cross and Alison Kemp and Paula Cawkill and Theo Sanderson and Cecile Crosnier and Nicole Muller-Sienerth and Doumbo, {Ogobara K.} and Boubacar Traore and Crompton, {Peter D.} and Pietro Cicuta and Tuan  Tran and Wright, {Gavin J.} and Rayner, {Julian C.}",
year = "2017",
month = "11",
day = "7",
doi = "10.1073/pnas.1702944114",
language = "English (US)",
volume = "114",
pages = "12045--12050",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "45",

}

TY - JOUR

T1 - Synergistic malaria vaccine combinations identified by systematic antigen screening

AU - Bustamante, Leyla Y.

AU - Powell, Gareth T.

AU - Lin, Yen Chun

AU - Macklin, Michael D.

AU - Cross, Nadia

AU - Kemp, Alison

AU - Cawkill, Paula

AU - Sanderson, Theo

AU - Crosnier, Cecile

AU - Muller-Sienerth, Nicole

AU - Doumbo, Ogobara K.

AU - Traore, Boubacar

AU - Crompton, Peter D.

AU - Cicuta, Pietro

AU - Tran, Tuan 

AU - Wright, Gavin J.

AU - Rayner, Julian C.

PY - 2017/11/7

Y1 - 2017/11/7

N2 - A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.

AB - A highly effective vaccine would be a valuable weapon in the drive toward malaria elimination. No such vaccine currently exists, and only a handful of the hundreds of potential candidates in the parasite genome have been evaluated. In this study, we systematically evaluated 29 antigens likely to be involved in erythrocyte invasion, an essential developmental stage during which the malaria parasite is vulnerable to antibody-mediated inhibition. Testing antigens alone and in combination identified several strain-transcending targets that had synergistic combinatorial effects in vitro, while studies in an endemic population revealed that combinations of the same antigens were associated with protection from febrile malaria. Video microscopy established that the most effective combinations targeted multiple discrete stages of invasion, suggesting a mechanistic explanation for synergy. Overall, this study both identifies specific antigen combinations for high-priority clinical testing and establishes a generalizable approach that is more likely to produce effective vaccines.

KW - Antigen combinations

KW - Erythrocyte invasion

KW - Malaria

KW - Plasmodium falciparum

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=85033437474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033437474&partnerID=8YFLogxK

U2 - 10.1073/pnas.1702944114

DO - 10.1073/pnas.1702944114

M3 - Article

VL - 114

SP - 12045

EP - 12050

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 45

ER -