The VP1 G-H loop hypervariable epitope contributes to protective immunity against foot and mouth disease virus in swine

Authors: FERNANDEZ-SAINZ, IGNACIO - University Of Connecticut; GAVITT, TYLER - University Of Connecticut; KOSTER, MARLA - Retired ARS Employee; RAMIREZ-MEDINA, ELIZABETH - Orise Fellow; RODRIGUEZ, YELITZA - Animal And Plant Health Inspection Service (APHIS); WU, PING - Animal And Plant Health Inspection Service (APHIS); SILBART, LAWRENCE - University Of Connecticut; De Los Santos, Teresa; SZCZEPANEK, STEVEN - University Of Connecticut

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/6/2019
Publication Date: 5/10/2019
Citation: Fernandez-Sainz, I., Gavitt, T.D., Koster, M., Ramirez-Medina, E., Rodriguez, Y.Y., Wu, P., Silbart, L.K., De Los Santos, T.B., Szczepanek, S.M. 2019. The VP1 G-H loop hypervariable epitope contributes to protective immunity against foot and mouth disease virus in swine. Vaccine. https://doi.org/10.1016/j.vaccine.2019.05.019.
DOI: https://doi.org/10.1016/j.vaccine.2019.05.019

Interpretive Summary: One of the main problems in foot and mouth disease (FMD) vaccinology is that FMD virus (FMDV) exists in multiple types and vaccination against one type of virus does not protect against another. It is thought that narrow immunity occurs because one specific region on the virus capsid dominates the host immune system, and over 25% of the antibodies induced by each vaccine type only recognize this particular virus region. We and others have previously shown that introduction of changes in the virus capsid could reduce the dominance of this region and vaccination with the modified vaccine induced a broader immune response in mice. Here we demonstrate that in contrast to mice, introduction of these modifications decreased rather than broadened, vaccine efficacy in swine. These results demonstrate that this region is not as flexible as thought and should be preserved in FMDV vaccine design to elicit adequate protection in swine at least against FMDV, at least for viruses of type O.

Technical 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, especially within immunodominant surface epitopes. 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 an epitope from PRRS virus on the immunogenicity and efficacy of an adenoviral vectored FMDV vaccine (Ad5-FMD). To assess the ability of the modified vaccine (denoted Ad5-FMDxeno) to prevent disease in swine, animals were vaccinated with Ad5-FMD, Ad5-FMDxeno, or PBS, followed by intradermal challenge with FDMV strain O1 Manisa at 21 days post-vaccination. Neutralizing antibody titers were decreased in pigs that received Ad5-FMDxeno, when compared to those vaccinated with Ad5-FMD, prior to viral challenge. As expected, animals vaccinated with unmodified Ad5-FMD were protected from lesions, fever and viremia. In contrast, animals vaccinated with Ad5-FMDxeno 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.