title: An oral microjet vaccination system elicits antibody production in rabbits.
abstract: Noninvasive immunization technologies have the potential to revolutionize global health by providing easy-to-administer vaccines at low cost, enabling mass immunizations during pandemics. Existing technologies such as transdermal microneedles are costly, deliver drugs slowly, and cannot generate mucosal immunity, which is important for optimal immunity against pathogens. We present a needle-free microjet immunization device termed MucoJet, which is a three-dimensional microelectromechanical systems-based drug delivery technology. MucoJet is administered orally, placed adjacent to the buccal tissue within the oral cavity, and uses a self-contained gas-generating chemical reaction within its two-compartment plastic housing to produce a high-pressure liquid jet of vaccine. We show that the vaccine jet ejected from the MucoJet device is capable of penetrating the buccal mucosal layer in silico, in porcine buccal tissue ex vivo, and in rabbits in vivo. Rabbits treated with ovalbumin by MucoJet delivery have antibody titers of anti-ovalbumin immunoglobulins G and A in blood serum and buccal tissue, respectively, that are three orders of magnitude higher than rabbits receiving free ovalbumin delivered topically by a dropper in the buccal region. MucoJet has the potential to accelerate the development of noninvasive oral vaccines, given its ability to elicit antibody production that is detectable locally in the buccal tissue and systemically via the circulation.
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA. karan@kgi.edu liepmann@berkeley.edu nmurthy@berkeley.edu.|School of Applied Life Sciences, Keck Graduate Institute, Claremont, CA 91711, USA.|Berkeley Sensor and Actuator Center, Berkeley, CA 94720, USA.|Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Kiana
authors.identifier: 0000-0003-0268-6192
authors.initials: K
authors.lastname: Aran
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.|UC Berkeley-UC San Francisco Graduate Program in Bioengineering, Berkeley and San Francisco, CA 94158, USA.|Berkeley Sensor and Actuator Center, Berkeley, CA 94720, USA.
authors.forename: Marc
authors.identifier: 0000-0002-6692-8237
authors.initials: M
authors.lastname: Chooljian
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.|Berkeley Sensor and Actuator Center, Berkeley, CA 94720, USA.|Center of Studies and Technical Research of Gipuzkoa and Tecnun (Technological Campus of the University of Navarra), 20018 San Sebastián, Spain.
authors.forename: Jacobo
authors.identifier: 0000-0002-0620-0770
authors.initials: J
authors.lastname: Paredes
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Rafi
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.|UC Berkeley-UC San Francisco Graduate Program in Bioengineering, Berkeley and San Francisco, CA 94158, USA.
authors.forename: Kunwoo
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.
authors.forename: Allison Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jeanny
authors.identifier: 0000-0003-2227-8161
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.
authors.forename: Jennifer F
authors.initials: JF
authors.lastname: Yau
authors.affiliation: Office of Laboratory Animal Care, UC Berkeley, Berkeley, CA 94720, USA.
authors.forename: Helen
authors.identifier: 0000-0002-0155-3016
authors.initials: H
authors.lastname: Chum
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA.|UC Berkeley-UC San Francisco Graduate Program in Bioengineering, Berkeley and San Francisco, CA 94158, USA.|Buck Institute for Research on Aging, Novato, CA 94945, USA.
authors.forename: Irina
authors.initials: I
authors.lastname: Conboy
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA. karan@kgi.edu liepmann@berkeley.edu nmurthy@berkeley.edu.|UC Berkeley-UC San Francisco Graduate Program in Bioengineering, Berkeley and San Francisco, CA 94158, USA.|Berkeley Sensor and Actuator Center, Berkeley, CA 94720, USA.
authors.forename: Niren
authors.identifier: 0000-0002-7815-7337
authors.initials: N
authors.lastname: Murthy
authors.affiliation: Department of Bioengineering, University of California (UC), Berkeley, Berkeley, CA 94720, USA. karan@kgi.edu liepmann@berkeley.edu nmurthy@berkeley.edu.|UC Berkeley-UC San Francisco Graduate Program in Bioengineering, Berkeley and San Francisco, CA 94158, USA.|Berkeley Sensor and Actuator Center, Berkeley, CA 94720, USA.
authors.forename: Dorian
authors.identifier: 0000-0002-2591-4031
authors.initials: D
authors.lastname: Liepmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000097:blood; D000917:Antibody Formation / Q000276:immunology*; D003198:Computer Simulation; D057446:Hydrodynamics; D018928:Immunity, Mucosal; D009061:Mouth Mucosa / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology; D011312:Pressure; D066330:Printing, Three-Dimensional; D011817:Rabbits; D034421:Sus scrofa; D014611:Vaccination / Q000295:instrumentation*
chemical_list: D000906:Antibodies; D010047:Ovalbumin