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Vaccines 2016, 4(3), 32;

Ag85A DNA Vaccine Delivery by Nanoparticles: Influence of the Formulation Characteristics on Immune Responses

School of Pharmaceutical Sciences, University of Geneva-University of Lausanne, Rue Michel Servet 1, 1211 Geneva, Switzerland
Vaccine Formulation Laboratory, Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, 1066 Epalinges, Switzerland
Author to whom correspondence should be addressed.
Academic Editor: Olga Borges
Received: 13 July 2016 / Revised: 16 August 2016 / Accepted: 5 September 2016 / Published: 12 September 2016
(This article belongs to the Special Issue Nanoparticles to Co-Deliver Immunopotentiators and Antigens)
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The influence of DNA vaccine formulations on immune responses in combination with adjuvants was investigated with the aim to increase cell-mediated immunity against plasmid DNA (pDNA) encoding Mycobacterium tuberculosis antigen 85A. Different ratios of pDNA with cationic trimethyl chitosan (TMC) nanoparticles were characterized for their morphology and physicochemical characteristics (size, zeta potential, loading efficiency and pDNA release profile) applied in vitro for cellular uptake studies and in vivo, to determine the dose-dependent effects of pDNA on immune responses. A selected pDNA/TMC nanoparticle formulation was optimized by the incorporation of muramyl dipeptide (MDP) as an immunostimulatory agent. Cellular uptake investigations in vitro showed saturation to a maximum level upon the increase in the pDNA/TMC nanoparticle ratio, correlating with increasing Th1-related antibody responses up to a definite pDNA dose applied. Moreover, TMC nanoparticles induced clear polarization towards a Th1 response, indicated by IgG2c/IgG1 ratios above unity and enhanced numbers of antigen-specific IFN-γ producing T-cells in the spleen. Remarkably, the incorporation of MDP in TMC nanoparticles provoked a significant additional increase in T-cell-mediated responses induced by pDNA. In conclusion, pDNA-loaded TMC nanoparticles are capable of provoking strong Th1-type cellular and humoral immune responses, with the potential to be further optimized by the incorporation of MDP. View Full-Text
Keywords: DNA vaccine; nanoparticles; N-trimethyl chitosan; adjuvants; cell-mediated immunity; tuberculosis DNA vaccine; nanoparticles; N-trimethyl chitosan; adjuvants; cell-mediated immunity; tuberculosis

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Poecheim, J.; Barnier-Quer, C.; Collin, N.; Borchard, G. Ag85A DNA Vaccine Delivery by Nanoparticles: Influence of the Formulation Characteristics on Immune Responses. Vaccines 2016, 4, 32.

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