Enhancing Antibody Response against Small Molecular Hapten with Tobacco Mosaic Virus as a Polyvalent Carrier.
Virus nanoparticles (VNPs) have been applied as carrier proteins for effective vaccine development. In this paper, we report the usage of tobacco mosaic virus (TMV) as a carrier for the display of the small molecule estriol (E3), a weakly immunogenic hapten. A highly efficient copper (I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC) was performed for the conjugation of E3 onto TMV capsid at tyrosine (Tyr) 139, by which the antigen density could be controlled. The immune properties of these constructs were evaluated in mice. We found that a strong and long-term antibody response was elicited by conjugating a high density of small molecular haptens on TMV through an oligo(ethylene glycol) (OEG) linker, likely due to the effective activation of B-cells. This study suggests that TMV can serve as a promising platform to induce strong humoral immune responses and that the optimized conjugation strategy was critical to produce high quality antibodies.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022 (China).
Xia
X
Zhao
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022 (China).
Limin
L
Chen
Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina, 29208 (USA).
Jittima Amie
JA
Luckanagul
Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina, 29208 (USA).
Xiaolei
X
Zhang
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, 5625 Renmin Street, Changchun 130022 (China). linyuan@ciac.jl.cn.
Yuan
Y
Lin
Department of Chemistry and Biochemistry, University of South Carolina, 631 Sumter Street, Columbia, South Carolina, 29208 (USA). wang263@mailbox.sc.edu.
Qian
Q
Wang
D000480:Alkynes / Q000737:chemistry; D000818:Animals; D000917:Antibody Formation; D001386:Azides / Q000737:chemistry; D036022:Capsid Proteins / Q000737:chemistry; D002460:Cell Line; D061565:Cycloaddition Reaction; D004337:Drug Carriers / Q000737:chemistry*; D004964:Estriol / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D019855:Ethylene Glycol / Q000737:chemistry; D006241:Haptens / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D007114:Immunization; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D014027:Tobacco Mosaic Virus / Q000737:chemistry*
D000480:Alkynes; D001386:Azides; D036022:Capsid Proteins; D004337:Drug Carriers; D006241:Haptens; D018796:Immunoconjugates; D004964:Estriol; D019855:Ethylene Glycol
antibodies; bioconjugation; hapten density; linkers; tobacco mosaic virus