DNA Vaccination Elicits Protective Immune Responses against Pandemic and Classic Swine Influenza Viruses in Pigs

Abstract

Swine influenza is a highly contagious viral infection in pigs that significantly impacts the pork industry due to weight loss and secondary infections. There is also the potential of a significant threat to public health, as was seen in 2009 when the pandemic H1N1 influenza virus strain emerged from reassortment events among avian, swine, and human influenza viruses within pigs. As classic and pandemic H1N1 strains now circulate in swine, an effective vaccine may be the best strategy to protect the pork industry and public health. Current inactivated-virus vaccines available for swine influenza protect only against viral strains closely related to the vaccine strain, and egg-based production of these vaccines is insufficient to respond to large outbreaks. DNA vaccines are a promising alternative since they can potentially induce broad-based protection with more efficient production methods. In this study we evaluated the potentials of monovalent and trivalent DNA vaccine constructs to (i) elicit both humoral and gamma interferon (IFN-␥) responses and (ii) protect pigs against viral shedding and lung disease after challenge with pandemic H1N1 or classic swine H1N1 influenza virus. We also compared the efficiency of a needle-free vaccine delivery method to that of a conventional needle/syringe injection. We report that DNA vaccination elicits robust serum antibody and cellular responses after three immunizations and confers significant protection against influenza virus challenge. Needle-free delivery elicited improved antibody responses with the same efficiency as conventional injection and should be considered for development as a practical alternative for vaccine administration.

Microneedles: an innovative platform for gene delivery

“…Gene delivery to the skin A number of physical strategies for the delivery of DNA therapeutics across the SC barrier have been investigated, achieving varying degrees of success, namely, intradermal injection [14], electroporation [15], liquid jet injection [16], gene gun delivery [16], tattooing [17] and MN delivery. Electroporation is currently the gold standard for delivery of macromolecules into the skin.…”

Vector optimization and needle-free intradermal application of a broadly protective polyvalent influenza A DNA vaccine for pigs and humans

“…The stream enables the fluid to penetrate across the skin's physical barriers, resulting in vaccine delivery into the different layers of the skin. Different needle-free injection systems have been tested successfully with influenza DNA plasmids in animals 21,32 and humans. 11 The needle-less IDAL Ò vaccinator (MSD Animal Health, Summit, NJ, US) is already used routinely for vaccination in swine herds for attenuated and inactivated protein vaccines against the Porcine Reproductive and Respiratory Syndrome virus, 33 Aujeszky's disease virus 34 and Mycoplasma hyopneumoniae 35,36 with promising results.…”

Immunogenicity and clinical protection against equine influenza by DNA vaccination of ponies

“…We have previously demonstrated the safety and immunogenicity of DNA vaccines in nonhuman primates and human clinical trials (29, 52, 62). We have also established efficacy, safety, and protection of DNA vaccines against H5N1 influenza in mice and chickens (48), as well as classic and pandemic H1N1 influenza in pigs (20). Here, we test the immunogenicity of monovalent and trivalent CMV/R-HA DNA vaccine constructs for EI in mice, and assess immune responses and protection against H3N8 challenge in ponies.…”

“…We have previously shown efficacy and efficiency of novel vaccination methods in various animal models, particularly needle-free delivery (20, 48, 56). Needle-free delivery offers the potential to enhance immune responses to DNA vaccination (16) and could facilitate wide-scale administration of vaccines by eliminating the need for handling and disposal of sharps.…”