Mechanistic Analysis of the Effect of Deamidation on the Immunogenicity of Anthrax Protective Antigen

Clinical and Vaccine Immunology : CVI
Anita VermaDrusilla L Burns

Abstract

The spontaneous modification of proteins, such as deamidation of asparagine residues, can significantly affect the immunogenicity of protein-based vaccines. Using a "genetically deamidated" form of recombinant protective antigen (rPA), we have previously shown that deamidation can decrease the immunogenicity of rPA, the primary component of new-generation anthrax vaccines. In this study, we investigated the biochemical and immunological mechanisms by which deamidation of rPA might decrease the immunogenicity of the protein. We found that loss of the immunogenicity of rPA vaccine was independent of the presence of adjuvant. We assessed the effect of deamidation on the immunodominant neutralizing B-cell epitopes of rPA and found that these epitopes were not significantly affected by deamidation. In order to assess the effect of deamidation on T-cell help for antibody production elicited by rPA vaccine, we examined the ability of the wild-type and genetically deamidated forms of rPA to serve as hapten carriers. We found that when wild-type and genetically deamidated rPA were modified to similar extents with 2,4-dinitrophenyl hapten (DNP) and then used to immunize mice, higher levels of anti-DNP antibodies were elicited by wild-typ...Continue Reading

References

Jan 19, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·D TleugabulovaE Pentón
Dec 13, 2000·The Journal of Biological Chemistry·B R SellmanR J Collier
Feb 7, 2001·Proceedings of the National Academy of Sciences of the United States of America·N E Robinson, A B Robinson
Apr 2, 2004·Nature Reviews. Immunology·N A Mitchison
Feb 3, 2005·The Journal of Biological Chemistry·LaToya S JonesC Russell Middaugh
Mar 8, 2005·The Journal of Biological Chemistry·Catherine X MossColin Watts
Mar 6, 2007·Annual Review of Biochemistry·John A T Young, R John Collier
Apr 18, 2008·Clinical and Vaccine Immunology : CVI·Kristian S OmlandUNKNOWN Participating Laboratories
Mar 19, 2009·Journal of the American Chemical Society·Jason J LavinderThomas J Magliery
Jul 30, 2009·Molecular Aspects of Medicine·Mahtab Moayeri, Stephen H Leppla
Apr 9, 2010·Clinical and Vaccine Immunology : CVI·Miriam M NgundiDrusilla L Burns
Jul 21, 2012·Clinical and Vaccine Immunology : CVI·Leslie WagnerDrusilla L Burns
Sep 14, 2012·Science Translational Medicine·Michael P FayEdwin O Nuzum
Jul 22, 2014·Immunology·Tal GefenJacob Pitcovski
Sep 5, 2014·Clinical and Vaccine Immunology : CVI·Ligong ChenConrad P Quinn

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Citations

Jul 13, 2019·Expert Review of Vaccines·Olga A KondakovaOlga V Karpova
Jul 3, 2020·Human Vaccines & Immunotherapeutics·Ekaterina M RyabchevskayaOlga V Karpova
Jan 24, 2021·Advanced Drug Delivery Reviews·Kendall B Preston, Theodore W Randolph
Jan 1, 2020·Molecular Therapy. Methods & Clinical Development·Jared A DelmarJohn P Mikhail
Jul 31, 2020·Expert Opinion on Biological Therapy·Manish ManishRakesh Bhatnagar
Apr 5, 2021·Journal of Pharmaceutical Sciences·Arvind SrivastavaGer Brophy
Oct 7, 2017·ACS Chemical Biology·Dylan L RiggsRyan R Julian

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