Development and statistical validation of a guinea pig model for vaccine potency testing against Infectious Bovine Rhinothracheitis (IBR) virus

Abstract

Infectious Bovine Rhinothracheitis (IBR) caused by bovine herpesvirus 1 (BoHV-1) infection is distributed worldwide. BoHV-1 either alone or in association with other respiratory cattle pathogens causes significant economic losses to the livestock industry. The aim of this work was to validate a guinea pig model as an alternative method to the current BoHV-1 vaccine potency testing in calves. Guinea pigs were immunized with two doses of vaccine, 21 days apart and sampled at 30 days post vaccination (dpv). BoHV-1 antibody (Ab) response to vaccination in guinea pigs, measured by ELISA and virus neutralization (VN), was statistically compared to the Ab response in cattle. The guinea pig model showed a dose-response relationship to the BoVH-1 antigen concentration in the vaccine and it was able to discriminate among vaccines containing 1log(10) difference in its BoHV-1 concentration with very good repeatability and reproducibility (CV < or = 20%). A regression analysis of the Ab titers obtained in guinea pigs and bovines at 30 and 60dpv, respectively, allowed us to classify vaccines in three potency categories: "very satisfactory", "satisfactory" and "unsatisfactory". Bovines immunized with vaccines corresponding to each of these three categories were experimentally challenged with BoVH-1 virus, the level of protection, as measured by reduction of virus shedding and disease severity, correlated well with the vaccine category used. Data generated by 85 experiments, which included vaccination of calves and guinea pigs with 18 reference vaccines of known potency, 8 placebos and 18 commercial vaccines, was subjected to statistical analysis. Concordance analysis indicated almost perfect agreement between the model and the target species for Ab titers measured by ELISA and almost perfect to substantial agreement when Ab titers were measured by VN. Taken together these results indicate that the developed guinea pig model represents a novel and reliable tool to estimate batch-to-batch vaccine potency and to predict efficacy of killed BoHV-1 veterinary vaccines.

Mouse model as an efficacy test for foot‐and‐mouth disease vaccines

“…The use of serologic tests represents a convenient alternative method to evaluate batch‐to‐batch vaccine potency (Parreño et al., 2010). Several authors have studied different serological tests involving humoral immunity parameters in order to partially replace PPG tests (Brito, Perez, & Capozzo, 2014; Capozzo et al., 1997; Lavoria et al., 2012; Maradei et al., 2008); however, these authors also propose that serum from vaccinated cattle continue to be used for different determinations.…”

First finding of genetic and antigenic diversity in 1b-BVDV isolates from Argentina

“…In consequence, it is important to highlight that our results of antigenic diversity were obtained from vaccinating guinea pigs, and it is difficult to compare them with the other works mentioned above. However, the guinea pig is the animal model used to test killed commercial formulations of reproductive and respiratory complex vaccines in Argentina; (Res SENASA 589/12) since the serology results in guinea pigs were statistically validated as a reliable indicator to predict vaccine immunogenicity in the natural host (Parreno et al, 2010).…”

Development of an enhanced bovine viral diarrhea virus subunit vaccine based on E2 glycoprotein fused to a single chain antibody which targets to antigen-presenting cells

“…589/12 related to animal health); since the levels of neutralizing antibodies induced in guinea pigs were statistically validated as a reliable indicator to predict vaccine immunogenicity in bovines. 7 For that reason, this animal model was chosen to test the vaccines developed in this work.…”