The VP1 G-H loop hypervariable epitope contributes to protective immunity against Foot and Mouth Disease Virus in swine

Ignacio Fernandez-Sainz; Tyler D Gavitt; Marla Koster; Elizabeth Ramirez-Medina; Yelitza Y Rodriguez; Ping Wu; Lawrence K Silbart; Teresa de Los Santos; Steven M Szczepanek

doi:10.1016/j.vaccine.2019.05.019

The VP1 G-H loop hypervariable epitope contributes to protective immunity against Foot and Mouth Disease Virus in swine

Vaccine. 2019 Jun 6;37(26):3435-3442. doi: 10.1016/j.vaccine.2019.05.019. Epub 2019 May 10.

Authors

Ignacio Fernandez-Sainz¹, Tyler D Gavitt², Marla Koster³, Elizabeth Ramirez-Medina⁴, Yelitza Y Rodriguez⁵, Ping Wu⁵, Lawrence K Silbart⁶, Teresa de Los Santos³, Steven M Szczepanek⁷

Affiliations

¹ Plum Island Animal Disease Center, Agricultural Research Services, North East Area, U.S Department of Agriculture, Orient, NY, USA; Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA.
² Centers of Excellence for Vaccine Research, University of Connecticut, Storrs, CT, USA; Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA.
³ Plum Island Animal Disease Center, Agricultural Research Services, North East Area, U.S Department of Agriculture, Orient, NY, USA.
⁴ Oak Ridge Institute for Science and Education, PIADC Research Participation Program, Oak Ridge, TN, USA.
⁵ Plum Island Animal Disease Center, Agricultural Research Services, North East Area, U.S Department of Agriculture, Orient, NY, USA; Plum Island Animal Disease Center, Animal and Plant Health Inspection Service, North East Area, U.S Department of Agriculture, Orient, NY, USA; Plum Island Animal Disease Center, Animal and Plant Health Inspection Service, National Veterinary Services Laboratory, North East Area, U.S Department of Agriculture, Orient, NY, USA.
⁶ Centers of Excellence for Vaccine Research, University of Connecticut, Storrs, CT, USA; Department of Allied Health Sciences, University of Connecticut, Storrs, CT, USA.
⁷ Centers of Excellence for Vaccine Research, University of Connecticut, Storrs, CT, USA; Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA. Electronic address: steven.szczepanek@uconn.edu.

PMID: 31085001
DOI: 10.1016/j.vaccine.2019.05.019

Abstract

Foot and Mouth Disease is a highly contagious and economically important disease of livestock. While vaccination is often effective at controlling viral spread, failures can occur due to strain mismatch or viral mutation. Foot and Mouth Disease Virus (FMDV) possesses a hypervariable region within the G-H Loop of VP1, a capsid protein commonly associated with virus neutralization. Here, we investigate the effect of replacement of the G-H loop hypervariable epitope with a xenoepitope from PRRS virus on the immunogenicity and efficacy of an adenovirus vectored FMDV vaccine (Ad5-FMD). Pigs were vaccinated with Ad5-FMD, the modified Ad5-FMD_xeno, or PBS, followed by intradermal challenge with FDMV strain O₁ Manisa at 21 days post-vaccination. While overall serum antibody titers were significantly higher in Ad5-FMD_xeno vaccinated animals, neutralizing antibody titers were decreased in pigs that received Ad5-FMD_xeno, when compared to those vaccinated with Ad5-FMD, prior to viral challenge, indicative of immune redirection away from VP1 towards non-neutralizing epitopes. As expected, animals vaccinated with unmodified Ad5-FMD were protected from lesions, fever, and viremia. In contrast, animals vaccinated with Ad5-FMD_xeno developed clinical signs and viremia, but at lower levels than that observed in PBS-treated controls. No significant difference was found in nasal shedding of virions between the two Ad5-FMD vaccinated groups. This data suggests that the hypervariable epitope of the VP1 G-H loop contributes to protective immunity conferred by Ad5 vector-delivered FMD vaccines in swine, and cannot be substituted without a loss of immunogenicity.

Keywords: Foot and Mouth Disease; G-H loop; Manisa; Serotype O(1); Vaccine; Xenoepitope.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenoviridae / immunology
Adenoviridae Infections / immunology
Animals
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology
Capsid Proteins / immunology*
Cell Line
Epitopes / immunology*
Foot-and-Mouth Disease / immunology*
Foot-and-Mouth Disease Virus / immunology*
Genetic Vectors / immunology
HEK293 Cells
Humans
Immunization / methods
Swine / immunology*
Vaccination / methods
Viral Vaccines / immunology

Substances

Antibodies, Neutralizing
Antibodies, Viral
Capsid Proteins
Epitopes
Viral Vaccines