Intradermal Vaccination against Influenza with a STING-Targeted Nanoparticle Combination Adjuvant Induces Superior Cross-Protective Humoral Immunity in Swine Compared with Intranasal and Intramuscular Immunization
Juan F. Hernandez-Franco,
Ganesh Yadagiri,
Veerupaxagouda Patil,
Dina Bugybayeva,
Sara Dolatyabi,
Ekachai Dumkliang,
Mithilesh Singh,
Raksha Suresh,
Fatema Akter,
Jennifer Schrock,
Gourapura J. Renukaradhya,
Harm HogenEsch
Affiliations
Juan F. Hernandez-Franco
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
Ganesh Yadagiri
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Veerupaxagouda Patil
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Dina Bugybayeva
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Sara Dolatyabi
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Ekachai Dumkliang
Drug Delivery System Excellence Center (DDSEC), Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, Thailand
Mithilesh Singh
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Raksha Suresh
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Fatema Akter
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Jennifer Schrock
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Gourapura J. Renukaradhya
Center for Food Animal Health, Department of Animal Sciences, The Ohio State University, Wooster, OH 44691, USA
Harm HogenEsch
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA
The development of cross-protective vaccines against the zoonotic swine influenza A virus (swIAV), a potential pandemic-causing agent, continues to be an urgent global health concern. Commercially available vaccines provide suboptimal cross-protection against circulating subtypes of swIAV, which can lead to worldwide economic losses and poor zoonosis deterrence. The limited efficacy of current swIAV vaccines demands innovative strategies for the development of next-generation vaccines. Considering that intramuscular injection is the standard route of vaccine administration in both human and veterinary medicine, the exploration of alternative strategies, such as intradermal vaccination, presents a promising avenue for vaccinology. This investigation demonstrates the first evaluation of a direct comparison between a commercially available multivalent swIAV vaccine and monovalent whole inactivated H1N2 swine influenza vaccine, delivered by intradermal, intranasal, and intramuscular routes. The monovalent vaccines were adjuvanted with NanoST, a cationic phytoglycogen-based nanoparticle that is combined with the STING agonist ADU-S100. Upon heterologous challenge, intradermal vaccination generated a stronger cross-reactive nasal and serum antibody response in pigs compared with intranasal and intramuscular vaccination. Antibodies induced by intradermal immunization also had higher avidity compared with the other routes of vaccination. Bone marrow from intradermally and intramuscularly immunized pigs had both IgG and IgA virus-specific antibody-secreting cells. These studies reveal that NanoST is a promising adjuvant system for the intradermal administration of STING-targeted influenza vaccines.
