Coinjection of a vaccine and anti-viral agents can provide fast-acting protection from foot-and-mouth disease

Antiviral Res. 2017 Jul:143:195-204. doi: 10.1016/j.antiviral.2017.04.009. Epub 2017 Apr 25.

Abstract

Foot-and-mouth disease (FMD) is the cause of an economically devastating animal disease. With commercial inactivated FMD vaccines, the protection against FMD virus (FMDV) begins a minimum of 4 days post vaccination (dpv). Therefore, antiviral agents could be proposed for rapid protection and to reduce the spread of FMDV during outbreaks until vaccine-induced protective immunity occurs. In previous studies, we have developed two recombinant adenoviruses that simultaneously express porcine interferon-α and interferon-γ (Ad-porcine IFN-αγ) and multiple siRNAs that target the non-structural protein-regions of FMDV (Ad-3siRNA), and we have shown that the combination of the two antiviral agents (referred to here as Ad combination) induced robust protection against FMDV in pigs. In an attempt to provide complete protection against FMDV, we co-administered Ad combination and the FMD vaccine to mice and pigs. In the C57BL/6 mice model, we observed rapid and continuous protection against homologous FMDV challenge from 1 to 3 dpv-the period in which vaccine-mediated immunity is absent. In the pig experiments, we found that most of the pigs (five out of six) that received vaccine + Ad combination and were challenged with FMDV at 1 or 2 dpv were clinically protected from FMDV. In addition, most of the pigs that received vaccine + Ad combination and all pigs inoculated with the vaccine only were clinically protected from an FMDV challenge at 7 dpv. We believe that the antiviral agent ensures early protection from FMDV, and the vaccine participates in protection after 7 dpv. Therefore, we can say that the combination of the FMD vaccine and effective antiviral agents may offer both fast-acting and continuous protection against FMDV. In further studies, we plan to design coadministration of Ad combination and novel vaccines.

Keywords: Antiviral agent; Co-administration; Foot-and-mouth disease; Interferon; Small interfering RNA; Vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antibodies, Neutralizing
  • Antibodies, Viral / immunology
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / pharmacology*
  • Cytokines / blood
  • Drug Combinations
  • Foot-and-Mouth Disease / prevention & control*
  • Foot-and-Mouth Disease Virus / drug effects*
  • Foot-and-Mouth Disease Virus / pathogenicity
  • HEK293 Cells
  • Humans
  • Injections, Intramuscular
  • Interferon-alpha / pharmacology
  • Interferon-gamma / pharmacology
  • Mice
  • Mice, Inbred C57BL
  • RNA, Small Interfering / pharmacology
  • Recombination, Genetic
  • Survival Rate
  • Swine
  • Vaccination*
  • Vaccines, Inactivated / pharmacology
  • Viral Nonstructural Proteins / immunology
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology
  • Viral Vaccines / pharmacology*

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antiviral Agents
  • Cytokines
  • Drug Combinations
  • Interferon-alpha
  • RNA, Small Interfering
  • Vaccines, Inactivated
  • Viral Nonstructural Proteins
  • Viral Vaccines
  • Interferon-gamma