Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity

Danika Lea Hill, Danny W Wilson, Natalia G Sampaio, Emily M Eriksson, Victoria Ryg-Cornejo, G. L. Abby Harrison, Alessandro D Uboldi, Leanne J Robinson, James G. Beeson, Peter Siba, Alan Frederick Cowman, Diana S. Hansen, Ivo Mueller, Louis Schofielda

Research output: Contribution to journalArticleResearchpeer-review

Abstract

It is unclear whether naturally acquired immunity to Plasmodium falciparum results from the acquisition of antibodies to multiple, diverse antigens or to fewer, highly conserved antigens. Moreover, the specific antibody functions required for malaria immunity are unknown, and hence informative immunological assays are urgently needed to address these knowledge gaps and guide vaccine development. In this study, we investigated whether merozoite-opsonizing antibodies are associated with protection from malaria in a strain-specific or strain-transcending manner by using a novel field isolate and an immune plasmamatched cohort from Papua New Guinea with our validated assay of merozoite phagocytosis. Highly correlated opsonization responses were observed across the 15 parasite strains tested, as were strong associations with protection (composite phagocytosis score across all strains in children uninfected at baseline: hazard ratio of 0.15, 95% confidence interval of 0.04 to 0.63). Opsonizing antibodies had a strong strain-transcending component, and the opsonization of transgenic parasites deficient for MSP3, MSP6, MSPDBL1, or P. falciparum MSP1-19 (PfMSP1-19) was similar to that of wild-type parasites. We have provided the first evidence that merozoite opsonization is predominantly strain transcending, and the highly consistent associations with protection against diverse parasite strains strongly supports the use of merozoite opsonization as a correlate of immunity for field studies and vaccine trials. These results demonstrate that conserved domains within merozoite antigens targeted by opsonization generate strain-transcending immune responses and represent promising vaccine candidates.

Original languageEnglish
Pages (from-to)2175-2184
Number of pages10
JournalInfection and Immunity
Volume84
Issue number8
DOIs
Publication statusPublished - Aug 2016

Cite this

Hill, D. L., Wilson, D. W., Sampaio, N. G., Eriksson, E. M., Ryg-Cornejo, V., Abby Harrison, G. L., ... Schofielda, L. (2016). Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity. Infection and Immunity, 84(8), 2175-2184. https://doi.org/10.1128/IAI.00145-16
Hill, Danika Lea ; Wilson, Danny W ; Sampaio, Natalia G ; Eriksson, Emily M ; Ryg-Cornejo, Victoria ; Abby Harrison, G. L. ; Uboldi, Alessandro D ; Robinson, Leanne J ; Beeson, James G. ; Siba, Peter ; Cowman, Alan Frederick ; Hansen, Diana S. ; Mueller, Ivo ; Schofielda, Louis. / Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity. In: Infection and Immunity. 2016 ; Vol. 84, No. 8. pp. 2175-2184.
@article{da81b8dcec6043ea981e541af792324e,
title = "Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity",
abstract = "It is unclear whether naturally acquired immunity to Plasmodium falciparum results from the acquisition of antibodies to multiple, diverse antigens or to fewer, highly conserved antigens. Moreover, the specific antibody functions required for malaria immunity are unknown, and hence informative immunological assays are urgently needed to address these knowledge gaps and guide vaccine development. In this study, we investigated whether merozoite-opsonizing antibodies are associated with protection from malaria in a strain-specific or strain-transcending manner by using a novel field isolate and an immune plasmamatched cohort from Papua New Guinea with our validated assay of merozoite phagocytosis. Highly correlated opsonization responses were observed across the 15 parasite strains tested, as were strong associations with protection (composite phagocytosis score across all strains in children uninfected at baseline: hazard ratio of 0.15, 95{\%} confidence interval of 0.04 to 0.63). Opsonizing antibodies had a strong strain-transcending component, and the opsonization of transgenic parasites deficient for MSP3, MSP6, MSPDBL1, or P. falciparum MSP1-19 (PfMSP1-19) was similar to that of wild-type parasites. We have provided the first evidence that merozoite opsonization is predominantly strain transcending, and the highly consistent associations with protection against diverse parasite strains strongly supports the use of merozoite opsonization as a correlate of immunity for field studies and vaccine trials. These results demonstrate that conserved domains within merozoite antigens targeted by opsonization generate strain-transcending immune responses and represent promising vaccine candidates.",
author = "Hill, {Danika Lea} and Wilson, {Danny W} and Sampaio, {Natalia G} and Eriksson, {Emily M} and Victoria Ryg-Cornejo and {Abby Harrison}, {G. L.} and Uboldi, {Alessandro D} and Robinson, {Leanne J} and Beeson, {James G.} and Peter Siba and Cowman, {Alan Frederick} and Hansen, {Diana S.} and Ivo Mueller and Louis Schofielda",
year = "2016",
month = "8",
doi = "10.1128/IAI.00145-16",
language = "English",
volume = "84",
pages = "2175--2184",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "8",

}

Hill, DL, Wilson, DW, Sampaio, NG, Eriksson, EM, Ryg-Cornejo, V, Abby Harrison, GL, Uboldi, AD, Robinson, LJ, Beeson, JG, Siba, P, Cowman, AF, Hansen, DS, Mueller, I & Schofielda, L 2016, 'Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity' Infection and Immunity, vol. 84, no. 8, pp. 2175-2184. https://doi.org/10.1128/IAI.00145-16

Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity. / Hill, Danika Lea; Wilson, Danny W; Sampaio, Natalia G; Eriksson, Emily M; Ryg-Cornejo, Victoria; Abby Harrison, G. L.; Uboldi, Alessandro D; Robinson, Leanne J; Beeson, James G.; Siba, Peter; Cowman, Alan Frederick; Hansen, Diana S.; Mueller, Ivo; Schofielda, Louis.

In: Infection and Immunity, Vol. 84, No. 8, 08.2016, p. 2175-2184.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity

AU - Hill, Danika Lea

AU - Wilson, Danny W

AU - Sampaio, Natalia G

AU - Eriksson, Emily M

AU - Ryg-Cornejo, Victoria

AU - Abby Harrison, G. L.

AU - Uboldi, Alessandro D

AU - Robinson, Leanne J

AU - Beeson, James G.

AU - Siba, Peter

AU - Cowman, Alan Frederick

AU - Hansen, Diana S.

AU - Mueller, Ivo

AU - Schofielda, Louis

PY - 2016/8

Y1 - 2016/8

N2 - It is unclear whether naturally acquired immunity to Plasmodium falciparum results from the acquisition of antibodies to multiple, diverse antigens or to fewer, highly conserved antigens. Moreover, the specific antibody functions required for malaria immunity are unknown, and hence informative immunological assays are urgently needed to address these knowledge gaps and guide vaccine development. In this study, we investigated whether merozoite-opsonizing antibodies are associated with protection from malaria in a strain-specific or strain-transcending manner by using a novel field isolate and an immune plasmamatched cohort from Papua New Guinea with our validated assay of merozoite phagocytosis. Highly correlated opsonization responses were observed across the 15 parasite strains tested, as were strong associations with protection (composite phagocytosis score across all strains in children uninfected at baseline: hazard ratio of 0.15, 95% confidence interval of 0.04 to 0.63). Opsonizing antibodies had a strong strain-transcending component, and the opsonization of transgenic parasites deficient for MSP3, MSP6, MSPDBL1, or P. falciparum MSP1-19 (PfMSP1-19) was similar to that of wild-type parasites. We have provided the first evidence that merozoite opsonization is predominantly strain transcending, and the highly consistent associations with protection against diverse parasite strains strongly supports the use of merozoite opsonization as a correlate of immunity for field studies and vaccine trials. These results demonstrate that conserved domains within merozoite antigens targeted by opsonization generate strain-transcending immune responses and represent promising vaccine candidates.

AB - It is unclear whether naturally acquired immunity to Plasmodium falciparum results from the acquisition of antibodies to multiple, diverse antigens or to fewer, highly conserved antigens. Moreover, the specific antibody functions required for malaria immunity are unknown, and hence informative immunological assays are urgently needed to address these knowledge gaps and guide vaccine development. In this study, we investigated whether merozoite-opsonizing antibodies are associated with protection from malaria in a strain-specific or strain-transcending manner by using a novel field isolate and an immune plasmamatched cohort from Papua New Guinea with our validated assay of merozoite phagocytosis. Highly correlated opsonization responses were observed across the 15 parasite strains tested, as were strong associations with protection (composite phagocytosis score across all strains in children uninfected at baseline: hazard ratio of 0.15, 95% confidence interval of 0.04 to 0.63). Opsonizing antibodies had a strong strain-transcending component, and the opsonization of transgenic parasites deficient for MSP3, MSP6, MSPDBL1, or P. falciparum MSP1-19 (PfMSP1-19) was similar to that of wild-type parasites. We have provided the first evidence that merozoite opsonization is predominantly strain transcending, and the highly consistent associations with protection against diverse parasite strains strongly supports the use of merozoite opsonization as a correlate of immunity for field studies and vaccine trials. These results demonstrate that conserved domains within merozoite antigens targeted by opsonization generate strain-transcending immune responses and represent promising vaccine candidates.

UR - http://www.scopus.com/inward/record.url?scp=84979779196&partnerID=8YFLogxK

U2 - 10.1128/IAI.00145-16

DO - 10.1128/IAI.00145-16

M3 - Article

VL - 84

SP - 2175

EP - 2184

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 8

ER -

Hill DL, Wilson DW, Sampaio NG, Eriksson EM, Ryg-Cornejo V, Abby Harrison GL et al. Merozoite antigens of plasmodium falciparum elicit strain-transcending opsonizing immunity. Infection and Immunity. 2016 Aug;84(8):2175-2184. https://doi.org/10.1128/IAI.00145-16