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Acquisition, maintenance and adaptation of invasion inhibitory antibodies against Plasmodium falciparum invasion ligands involved in immune evasion

Tijani, Muyideen K.; Babalola, Oluwatoyin A.; Odaibo, Alex B.; Anumudu, Chiaka I.; Asinobi, Adanze O.; Morenikeji, Olajumoke A.; Asuzu, Michael C.; Langer, Christine; Reiling, Linda and Beeson, James G., et al. (2017) In PLoS ONE 12(8).
Abstract

Erythrocyte-binding antigens (EBAs) and P. falciparum reticulocyte-binding homologue proteins (PfRhs) are two important protein families that can vary in expression and utilization by P. falciparum to evade inhibitory antibodies. We evaluated antibodies at repeated time-points among individuals living in an endemic region in Nigeria over almost one year against these vaccine candidates. Antibody levels against EBA140, EBA175, EBA181, PfRh2, PfRh4, and MSP2, were measured by ELISA. We also used parasites with disrupted EBA140, EBA175 and EBA181 genes to show that all these were targets of invasion inhibitory antibodies. However, antigenic targets of inhibitory antibodies were not stable and changed substantially over time in most... (More)

Erythrocyte-binding antigens (EBAs) and P. falciparum reticulocyte-binding homologue proteins (PfRhs) are two important protein families that can vary in expression and utilization by P. falciparum to evade inhibitory antibodies. We evaluated antibodies at repeated time-points among individuals living in an endemic region in Nigeria over almost one year against these vaccine candidates. Antibody levels against EBA140, EBA175, EBA181, PfRh2, PfRh4, and MSP2, were measured by ELISA. We also used parasites with disrupted EBA140, EBA175 and EBA181 genes to show that all these were targets of invasion inhibitory antibodies. However, antigenic targets of inhibitory antibodies were not stable and changed substantially over time in most individuals, independent of age. Antibodies levels measured by ELISA also varied within and between individuals over time and the antibodies against EBA181, PfRh2 and MSP2 declined more rapidly in younger individuals (15 years) compared with older (>15). The breadth of high antibody responses over time was more influenced by age than by the frequency of infection. High antibody levels were associated with a more stable invasion inhibitory response, which could indicate that during the long process of formation of immunity, many changes not only in levels but also in functional responses are needed. This is an important finding in understanding natural immunity against malaria, which is essential for making an efficacious vaccine.

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PLoS ONE
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8
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Public Library of Science
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  • scopus:85026861473
  • wos:000406998800018
ISSN
1932-6203
DOI
10.1371/journal.pone.0182187
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English
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yes
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d45cd4bf-c2a1-4e27-b5a0-f50c8103c3f1
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2017-08-23 15:24:32
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2017-09-18 11:42:52
@article{d45cd4bf-c2a1-4e27-b5a0-f50c8103c3f1,
  abstract     = {<p>Erythrocyte-binding antigens (EBAs) and P. falciparum reticulocyte-binding homologue proteins (PfRhs) are two important protein families that can vary in expression and utilization by P. falciparum to evade inhibitory antibodies. We evaluated antibodies at repeated time-points among individuals living in an endemic region in Nigeria over almost one year against these vaccine candidates. Antibody levels against EBA140, EBA175, EBA181, PfRh2, PfRh4, and MSP2, were measured by ELISA. We also used parasites with disrupted EBA140, EBA175 and EBA181 genes to show that all these were targets of invasion inhibitory antibodies. However, antigenic targets of inhibitory antibodies were not stable and changed substantially over time in most individuals, independent of age. Antibodies levels measured by ELISA also varied within and between individuals over time and the antibodies against EBA181, PfRh2 and MSP2 declined more rapidly in younger individuals (15 years) compared with older (&gt;15). The breadth of high antibody responses over time was more influenced by age than by the frequency of infection. High antibody levels were associated with a more stable invasion inhibitory response, which could indicate that during the long process of formation of immunity, many changes not only in levels but also in functional responses are needed. This is an important finding in understanding natural immunity against malaria, which is essential for making an efficacious vaccine.</p>},
  articleno    = {e0182187},
  author       = {Tijani, Muyideen K. and Babalola, Oluwatoyin A. and Odaibo, Alex B. and Anumudu, Chiaka I. and Asinobi, Adanze O. and Morenikeji, Olajumoke A. and Asuzu, Michael C. and Langer, Christine and Reiling, Linda and Beeson, James G. and Wahlgren, Mats and Nwuba, Roseangela I. and Persson, Kristina E.M.},
  issn         = {1932-6203},
  language     = {eng},
  month        = {08},
  number       = {8},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Acquisition, maintenance and adaptation of invasion inhibitory antibodies against Plasmodium falciparum invasion ligands involved in immune evasion},
  url          = {http://dx.doi.org/10.1371/journal.pone.0182187},
  volume       = {12},
  year         = {2017},
}