ELISA units, IgG subclass ratio and avidity determined functional activity of mouse anti-Pfs230 antibodies judged by a standard membrane-feeding assay with Plasmodium falciparum

•Multiple mouse anti-Pfs230 antibodies were generated for ELISA and SMFA tests.•There was a significant correlation between ELISA titer and SMFA activity.•However, ELISA titer alone was a poor predictor of functional activity.•Both IgG2/IgG1 ratio and avidity significantly affected functional activi...

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Bibliographic Details
Published in:Vaccine 2019-04, Vol.37 (15), p.2073-2078
Main Authors: Miura, Kazutoyo, Deng, Bingbing, Wu, Yimin, Zhou, Luwen, Pham, Thao P., Diouf, Ababacar, Wu, Chia-Kuei, Lee, Shwu-Maan, Plieskatt, Jordan L., Morin, Merribeth J., Long, Carole A.
Format: Article
Language:English
Subjects:
Adjuvants
Animal models
Animals
Anopheles - parasitology
Antibodies, Protozoan - immunology
Antibody Affinity
Antigens, Protozoan - classification
Antigens, Protozoan - immunology
Assaying
Avidity
Biological activity
Dosage
Enzyme-Linked Immunosorbent Assay
Feeding
Female
IgG subclass
Immunization
Immunoglobulin G
Immunoglobulin G - classification
Immunoglobulin G - immunology
Malaria
Malaria Vaccines - immunology
Malaria, Falciparum - immunology
Malaria, Falciparum - prevention & control
Mice
Monoclonal antibodies
Mosquitoes
Parasites
Pfs230
Plasmodium falciparum
Plasmodium falciparum - immunology
Proteins
Rank tests
Regression analysis
Standard membrane-feeding assay
Transmission-blocking vaccine
Vaccine development
Vaccines
Vector-borne diseases
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Summary:•Multiple mouse anti-Pfs230 antibodies were generated for ELISA and SMFA tests.•There was a significant correlation between ELISA titer and SMFA activity.•However, ELISA titer alone was a poor predictor of functional activity.•Both IgG2/IgG1 ratio and avidity significantly affected functional activity. The standard membrane-feeding assay (SMFA) is a functional assay that has been used to inform the development of transmission-blocking vaccines (TBV) against Plasmodium falciparum malaria. For Pfs230, a lead target antigen for TBV development, a few studies have tested either a single anti-Pfs230 polyclonal or monoclonal antibody (one antibody per study) at serial dilutions and showed a dose-dependent response. Further, there have been reports that the SMFA activity of anti-Pfs230 polyclonal and monoclonal antibodies were enhanced in the presence of complement. However, no analysis has been performed with multiple samples, and the impact of anti-Pfs230 antibody titers, IgG subclass profile and avidity were evaluated together in relation to transmission-reducing activity (TRA) by SMFA. In this report, a total of 39 unique anti-Pfs230 IgGs from five different mouse immunization studies were assessed for their ELISA units (EU), IgG2/IgG1 ratio and avidity by ELISA, and the functionality (% transmission-reducing activity, %TRA) by SMFA. The mice were immunized with Pfs230 alone, Pfs230 conjugated to CRM197, or a mixture of unconjugated Pfs230 and CRM197 proteins using Alhydrogel or Montanide ISA720 adjuvants. In all studies, the Pfs230 antigen was from the same source. There was a significant correlation between EU and %TRA (p 
ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2019.02.071