title: Toll-Like Receptor 9 Activation Rescues Impaired Antibody Response in Needle-free Intradermal DNA Vaccination.
abstract: The delivery of plasmid DNA to the skin can target distinct subsets of dermal dendritic cells to confer a superior immune response. The needle-free immunization technology offers a reliable, safe and efficient means to administer intradermal (ID) injections. We report here that the ID injection of DNA vectors using an NF device (NF-ID) elicits a superior cell-mediated immune response, at much lesser DNA dosage, comparable in magnitude to the traditional intramuscular immunization. However, the humoral response is significantly impaired, possibly at the stage of B cell isotype switching. We found that the NF-ID administration deposits the DNA primarily on the epidermis resulting in a rapid loss of the DNA as well as the synthesized antigen due to the faster regeneration rate of the skin layers. Therefore, despite the immune-rich nature of the skin, the NF-ID immunization of DNA vectors may be limited by the impaired humoral response. Additional booster injections are required to augment the antibody response. As an alternative and a viable solution, we rescued the IgG response by coadministration of a Toll-like receptor 9 agonist, among other adjuvants examined. Our work has important implication for the optimization of the emerging needle-free technology for ID immunization.
authors.affiliation: HIV - AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Bengaluru, India.
authors.forename: Prabhu S
authors.initials: PS
authors.lastname: Arunachalam
authors.affiliation: HIV - AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Bengaluru, India.
authors.forename: Ria
authors.initials: R
authors.lastname: Mishra
authors.affiliation: Institute for Stem Cell Biology and Regenerative Medicine, Bengaluru, India.
authors.forename: Krithika
authors.initials: K
authors.lastname: Badarinath
authors.affiliation: HIV - AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Bengaluru, India.
authors.forename: Deepak
authors.initials: D
authors.lastname: Selvam
authors.affiliation: HIV - AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Bengaluru, India.
authors.forename: Sravan K
authors.initials: SK
authors.lastname: Payeli
authors.affiliation: Bioject Medical Technologies Inc., Oregon, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Stout
authors.affiliation: HIV - AIDS Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Center for Advanced Scientific Research, Bengaluru, India.
authors.forename: Udaykumar
authors.initials: U
authors.lastname: Ranga