Back to Journals » International Journal of Nanomedicine » Volume 9 » Issue 1

Cryogenic transmission electron microscopy of recombinant tuberculosis vaccine antigen with anionic liposomes reveals formation of flattened liposomes

Authors Fox CB, Mulligan SK, Sung J, Dowling QM, Fung HWM, Vedvick TS, Coler RN

Received 25 October 2013

Accepted for publication 17 December 2013

Published 11 March 2014 Volume 2014:9(1) Pages 1367—1377

DOI https://doi.org/10.2147/IJN.S56582

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Supplementary video 1

Views: 424

Christopher B Fox,1 Sean K Mulligan,2 Joyce Sung,2 Quinton M Dowling,1 H W Millie Fung,1 Thomas S Vedvick,1 Rhea N Coler1

1Infectious Disease Research Institute, Seattle, WA, USA; 2NanoImaging Services, La Jolla, CA, USA

Abstract: Development of lipid-based adjuvant formulations to enhance the immunogenicity of recombinant vaccine antigens is a focus of modern vaccine research. Characterizing interactions between vaccine antigens and formulation excipients is important for establishing compatibility between the different components and optimizing vaccine stability and potency. Cryogenic transmission electron microscopy (TEM) is a highly informative analytical technique that may elucidate various aspects of protein- and lipid-based structures, including morphology, size, shape, and phase structure, while avoiding artifacts associated with staining-based TEM. In this work, cryogenic TEM is employed to characterize a recombinant tuberculosis vaccine antigen, an anionic liposome formulation, and antigen–liposome interactions. By performing three-dimensional tomographic reconstruction analysis, the formation of a population of protein-containing flattened liposomes, not present in the control samples, was detected. It is shown that cryogenic TEM provides unique information regarding antigen–liposome interactions not detectable by light-scattering-based methods. Employing a suite of complementary analytical techniques is important to fully characterize interactions between vaccine components.

Keywords: vaccine adjuvant; cryo-TEM; antigen-adjuvant interactions; vaccine physical characterization; vaccine formulation morphology; 3D tomographic reconstruction

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]

 

Readers of this article also read:

Pluronic® L64-mediated stable HIF-1α expression in muscle for therapeutic angiogenesis in mouse hindlimb ischemia

Song H, Liu S, Li C, Geng Y, Wang G, Gu Z

International Journal of Nanomedicine 2014, 9:3439-3452

Published Date: 21 July 2014

Green synthesis of water-soluble nontoxic polymeric nanocomposites containing silver nanoparticles

Prozorova GF, Pozdnyakov AS, Kuznetsova NP, Korzhova SA, Emel’yanov AI, Ermakova TG, Fadeeva TV, Sosedova LM

International Journal of Nanomedicine 2014, 9:1883-1889

Published Date: 16 April 2014

Methacrylic-based nanogels for the pH-sensitive delivery of 5-Fluorouracil in the colon

Ashwanikumar N, Kumar NA, Nair SA, Kumar GS

International Journal of Nanomedicine 2012, 7:5769-5779

Published Date: 15 November 2012

A novel preparation method for silicone oil nanoemulsions and its application for coating hair with silicone

Hu Z, Liao M, Chen Y, Cai Y, Meng L, Liu Y, Lv N, Liu Z, Yuan W

International Journal of Nanomedicine 2012, 7:5719-5724

Published Date: 12 November 2012

Cross-linked acrylic hydrogel for the controlled delivery of hydrophobic drugs in cancer therapy

Deepa G, Thulasidasan AK, Anto RJ, Pillai JJ, Kumar GS

International Journal of Nanomedicine 2012, 7:4077-4088

Published Date: 27 July 2012

Servant leadership: a case study of a Canadian health care innovator

Vanderpyl TH

Journal of Healthcare Leadership 2012, 4:9-16

Published Date: 16 February 2012

Crystallization after intravitreal ganciclovir injection

Pitipol Choopong, Nattaporn Tesavibul, Nattawut Rodanant

Clinical Ophthalmology 2010, 4:709-711

Published Date: 14 July 2010