Dataset Information

Standardized guinea pig model for Q fever vaccine reactogenicity.

ABSTRACT: Historically, vaccination with Coxiella burnetii whole cell vaccines has induced hypersensitivity reactions in humans and animals that have had prior exposure to the pathogen as a result of infection or vaccination. Intradermal skin testing is routinely used to evaluate exposure in humans, and guinea pig hypersensitivity models have been developed to characterize the potential for reactogenicity in vaccine candidates. Here we describe a refinement of the guinea pig model using an alternate vaccine for positive controls. An initial comparative study used viable C. burnetii to compare the routes of sensitizing exposure of guinea pigs (intranasal vs intraperitoneal), evaluation of two time points for antigen challenge (21 and 42 days) and an assessment of two routes (intradermal and subcutaneous) of challenge using the ruminant vaccine Coxevac as the antigenic control. Animals sensitized by intraperitoneal exposure exhibited slightly larger gross reactions than did those sensitized by intranasal exposure, and reactions were more pronounced when skin challenge was performed at 42 days compared to 21 days post-sensitization. The intradermal route proved to be the optimal route of reactogenicity challenge. Histopathological changes at injection sites were similar to those previously reported and a scoring system was developed to compare reactions between groups receiving vaccine by intradermal versus subcutaneous routes. Based on the comparative study, a standardized protocol for assessment of vaccine reactogenicity in intranasally-sensitized animals was tested in a larger confirmatory study. Results suggest that screens utilizing a group size of n = 3 would achieve 90% power for detecting exposure-related reactogenic responses of the magnitude induced by Coxevac using either of two outcome measures.

SUBMITTER: Baeten LA

PROVIDER: S-EPMC6185858 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Standardized guinea pig model for Q fever vaccine reactogenicity.

Baeten Laurie A LA Podell Brendan K BK Sluder Ann E AE Garritsen Anja A Bowen Richard A RA Poznansky Mark C MC

PloS one 20181012 10

Historically, vaccination with Coxiella burnetii whole cell vaccines has induced hypersensitivity reactions in humans and animals that have had prior exposure to the pathogen as a result of infection or vaccination. Intradermal skin testing is routinely used to evaluate exposure in humans, and guinea pig hypersensitivity models have been developed to characterize the potential for reactogenicity in vaccine candidates. Here we describe a refinement of the guinea pig model using an alternate vacci ...[more]

PMID: 30312355

Similar Datasets

Project description: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.

Project description:Herpes simplex virus (HSV) infections are common and can cause severe illness but no vaccine is currently available. The recent failure of subunit HSV vaccines has highlighted the need for vaccines that present a diverse array of antigens, including the development of next-generation live-attenuated vaccines. However, most attenuated HSV strains propagate poorly, limiting their ability to elicit protective immune responses. A live-attenuated vaccine that replicates in non-neural tissue but is ablated for transmission into the nervous system may elicit protective immune responses without evoking neurologic complications or establishing life-long infections. Initial studies of R2, a live-attenuated vaccine that is engineered to be unable to invade the nervous system, used the guinea pig genital HSV model to evaluate the ability of R2 to replicate at the site of inoculation, cause disease and infect neural tissues. R2 was then evaluated as a vaccine using three routes of inoculation: intramuscular (IM), intradermal (ID) and intravaginal (IVag) and compared to IM administered gD2+MPL/Alum vaccine in the same model. R2 replicated in the genital tract but did not produce acute or recurrent disease and did not infect the neural tissue. The R2 vaccine-induced neutralizing antibody and decreased the severity of acute and recurrent HSV-2 disease as well as recurrent shedding. The ID route was the most effective. ID administered R2 was more effective than gD2+MPL/Alum at inducing neutralizing antibody, suppressing acute disease, and acute vaginal virus replication. R2 was especially more effective at reducing recurrent virus shedding, the most common source of HSV transmission. The live-attenuated prophylactic HSV vaccine, R2, was effective in the guinea pig model of genital HSV-2 especially when administered by the ID route. The use of live-attenuated HSV vaccines that robustly replicate in mucosal tissues but are ablated for neuroinvasion offers a promising approach for HSV vaccines.

Dataset Information

Standardized guinea pig model for Q fever vaccine reactogenicity.

Publications

Standardized guinea pig model for Q fever vaccine reactogenicity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets