title: Cross-protection by co-immunization with influenza hemagglutinin DNA and inactivated virus vaccine using coated microneedles.
abstract: The need for annual revaccination against influenza is a burden on the healthcare system, leads to low vaccination rates and makes timely vaccination difficult against pandemic strains, such as during the 2009 H1N1 influenza pandemic. In an effort toward achieving a broadly protective vaccine that provides cross-protection against multiple strains of influenza, this study developed a microneedle patch to co-immunize with A/PR8 influenza hemagglutinin DNA and A/PR8 inactivated virus vaccine. We hypothesize that this dual component vaccination strategy administered to the skin using microneedles will provide cross-protection against other strains of influenza. To test this hypothesis, we developed a novel coating formulation that did not require additional excipients to increase coating solution viscosity by using the DNA vaccine itself to increase viscosity and thereby enable thick coatings of DNA vaccine and inactivated virus vaccine on metal microneedles. Co-immunization in this way not only generated robust antibody responses against A/PR8 influenza but also generated robust heterologous antibody responses against pandemic 2009 H1N1 influenza in mice. Challenge studies showed complete cross-protection against lethal challenge with live pandemic 2009 H1N1 virus. Control experiments using A/PR8 inactivated influenza virus vaccine with placebo DNA coated onto microneedles produced lower antibody titers and provided incomplete protection against challenge. Overall, this is the first study showing DNA solution as a microneedle coating agent and demonstrating cross-protection by co-immunization with inactivated virus and DNA vaccine using coated microneedles.
authors: Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Republic of Korea. Electronic address: dohnanyi@kaist.ac.kr.
authors: Yeu-Chun
authors: YC
authors: Kim
authors: Dae-Goon
authors: DG
authors: Yoo
authors: Richard W
authors: RW
authors: Compans
authors: Sang-Moo
authors: SM
authors: Kang
authors: Mark R
authors: MR
authors: Prausnitz
mesh_terms: D000818:Animals; D000917:Antibody Formation; D016503:Drug Delivery Systems / Q000295:instrumentation*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics*; D006801:Humans; D007114:Immunization; D053118:Influenza A Virus, H1N1 Subtype / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control; D007271:Injections, Intradermal; D051379:Mice; D008807:Mice, Inbred BALB C; D009339:Needles; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000276:immunology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019444:Vaccines, DNA; D015164:Vaccines, Inactivated
keywords: Coating; Cross-protection; DNA vaccine; Influenza virus; Microneedle
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