Skin Vaccination against Rotavirus Using Microneedles: Proof of Concept in Gnotobiotic Piglets.
Live-attenuated oral rotavirus (RV) vaccines have lower efficacy in low income countries, and additionally are associated with a rare but severe adverse event, intussusception. We have been pursuing the development of an inactivated rotavirus vaccine (IRV) using the human rotavirus strain CDC-9 (G1P[8]) through parenteral immunization and previously demonstrated dose sparing and enhanced immunogenicity of intradermal (ID) unadjuvanted IRV using a coated microneedle patch in comparison with intramuscular (IM) administration in mice. The aim of this study was to evaluate the immune response and protection against RV infection and diarrhea conferred by the administration of the ID unadjuvanted IRV using the microneedle device MicronJet600® in neonatal gnotobiotic (Gn) piglets challenged with virulent Wa G1P[8] human RV. Three doses of 5 μg IRV when administered intradermally and 5 μg IRV formulated with aluminum hydroxide [Al(OH)3] when administered intramuscularly induced comparable rotavirus-specific antibody titers of IgA, IgG, IgG avidity index and neutralizing activity in sera of neonatal piglets. Both IRV vaccination regimens protected against RV antigen shedding in stools, and reduced the cumulative diarrhea scores in the piglets. This study demonstrated that the ID and IM administrations of IRV are immunogenic and protective against RV-induced diarrhea in neonatal piglets. Our findings highlight the potential value of an adjuvant sparing effect of the IRV ID delivery route.
Gastroenteritis and Respiratory Viruses Laboratory Branch Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Yuhuan
Y
Wang
Food Animal Health Research Program, Ohio Agricultural Research & Development Center, The Ohio State University, Wooster, Ohio, United States of America.
Anastasia
A
Vlasova
Gastroenteritis and Respiratory Viruses Laboratory Branch Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Daniel E
DE
Velasquez
Food Animal Health Research Program, Ohio Agricultural Research & Development Center, The Ohio State University, Wooster, Ohio, United States of America.
Linda J
LJ
Saif
Food Animal Health Research Program, Ohio Agricultural Research & Development Center, The Ohio State University, Wooster, Ohio, United States of America.
Sukumar
S
Kandasamy
NanoPass Technologies Ltd., Nes Ziona, Israel.
Efrat
E
Kochba
NanoPass Technologies Ltd., Nes Ziona, Israel.
Yotam
Y
Levin
Gastroenteritis and Respiratory Viruses Laboratory Branch Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
Baoming
B
Jiang
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D005856:Germ-Free Life / Q000276:immunology*; D007271:Injections, Intradermal / Q000662:veterinary; D008845:Microinjections / Q000379:methods / Q000662:veterinary; D012401:Rotavirus / Q000276:immunology*; D012400:Rotavirus Infections / Q000276:immunology / Q000517:prevention & control / Q000662:veterinary*; D022243:Rotavirus Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D013552:Swine / Q000276:immunology / Q000821:virology; D013553:Swine Diseases / Q000276:immunology / Q000517:prevention & control* / Q000821:virology
D000914:Antibodies, Viral; D022243:Rotavirus Vaccines