Differences in affinity of monoclonal and naturally acquired polyclonal antibodies against Plasmodium falciparum merozoite antigens

BMC Microbiology

Kristina E.M. Persson¹  James G. Beeson²  Fred Kironde⁷  Mats Wahlgren⁵  Peter M. Siba⁹  Danielle I. Stanisic³  Nicolas Senn⁸  Ivo Mueller⁹  Nadia Cross⁴  Robin F. Anders⁶  Sreenivasulu B. Reddy⁵ 

[1] Department of Laboratory Medicine, Lund University, Lund, 22185, Sweden;The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia;Institute for Glycomics, Griffith University, Queensland, Australia;The Macfarlane Burnet Institute for Medical Research and Public Health, Melbourne, Victoria, Australia;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 171 77, Sweden;Department of Biochemistry, La Trobe University, Vic 3086, Australia;Habib Medical School, IUIU, Kampala, Uganda;Swiss Tropical and Public Health Institute, Basel, Switzerland;Papua New Guinea Institute of Medical Research, Goroka 441, Papua New Guinea

关键词: Parasitology;    Malaria;    Immunology;    Falciparum;    Antigen;    Antibodies;   

Others  :  1227630
DOI  :  10.1186/s12866-015-0461-1

 received in 2014-10-30, accepted in 2015-06-03,  发布年份 2015

【 摘 要 】

Background

Malaria is a major global cause of deaths and a vaccine is urgently needed.

Results

We have employed the P. falciparum merozoite antigens MSP2-3D7/FC27 and AMA1, used them in ELISA, and coupled them in different ways using surface plasmon resonance (SPR) and estimated affinity (measured as k _d ) of monoclonal as well as naturally-acquired polyclonal antibodies in human plasma. There were major differences in k _ddepending on how the antigens were immobilized and where the His-tag was placed. For AMA1 we could see correlations with invasion inhibition. Using different immobilizations of proteins in SPR, we could see only moderate correlations with levels of antibodies in ELISA, indicating that in ELISA the proteins were not uniformly bound and that antibodies with many specificities exist in natural immunisation. The correlations between ELISA and SPR were enhanced when only parasite positive samples were included, which may indicate that high affinity antibodies are difficult to maintain over long periods of time. We found higher k _dvalues for MSP2 (indicating lower affinity) compared to AMA1, which might be partly explained by MSP2 being an intrinsically disordered protein, while AMA1 is globular.

Conclusions

For future vaccine studies and for understanding immunity, it is important to consider how to present proteins to the immune system to achieve highest antibody affinities.

【 授权许可】

   
2015 Reddy et al.

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