Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant.
Vaccines are commonly administered by injection using needles. Although transdermal microneedles are less-invasive promising alternatives, needle-free topical vaccination without involving physical damage to the natural skin barrier is still sought after as it can further reduce needle-induced anxiety and simply administration. However, this long-standing goal has been elusive since the intact skin is impermeable to most macromolecules. Here, we show an efficient, non-invasive transdermal vaccination in mice by employing two key innovations: first, the use of hyaluronan (HA) as vaccine carriers and, second, non-ablative laser adjuvants. Conjugates of a model vaccine ovalbumin (OVA) and HA-HA-OVA conjugates-induced more effective maturation of dendritic cellsin vitro, compared to OVA or HA alone, through synergistic HA receptor-mediated effects. Following topical administration in the back skin, HA-OVA conjugates penetrated into the epidermis and dermis in murine and porcine skins up to 30% of the total applied quantity, as revealed by intravital microscopy and quantitative fluorescence assay. Topical administration of HA-OVA conjugates significantly elevated both anti-OVA IgG antibody levels in serum and IgA antibody levels in bronchioalveolar lavage, with peak levels at 4 weeks, while OVA alone had a negligible effect. An OVA challenge at week 8 elicited strong immune-recall humoral responses. With pre-treatment of the skin using non-ablative fractional laser beams (1410 nm wavelength, 10 ms pulse duration, 0.2 mJ/pulse) as laser adjuvant, strong immunization was achieved with much reduced doses of HA-OVA (1 mg/kg OVA). Our results demonstrate the potential of the non-invasive patch-type transdermal vaccination platform.
Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St., UP-5, Cambridge, Massachusetts 02139, USA.
Ki Su
KS
Kim
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 790-784, Korea.
Hyemin
H
Kim
Division of Integrative Biosciences and Biotechnology, POSTECH, 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 790-784, Korea.
Yunji
Y
Park
Department of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 790-784, Korea.
Won Ho
WH
Kong
Division of Integrative Biosciences and Biotechnology, POSTECH, 77 Cheongam-Ro, Nam-gu, Pohang, Gyeongbuk 790-784, Korea.
Seung Woo
SW
Lee
Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St., UP-5, Cambridge, Massachusetts 02139, USA.
Sheldon J J
SJ
Kwok
Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St., UP-5, Cambridge, Massachusetts 02139, USA.
Sei Kwang
SK
Hahn
Wellman Center for Photomedicine, Massachusetts General Hospital, 65 Landsdowne St., UP-5, Cambridge, Massachusetts 02139, USA.
Seok Hyun
SH
Yun
Hyaluronan; Immunization; Laser adjuvant; Non-invasive; Transdermal Immunization; Transdermal delivery; Vaccine