# Intranasal Inoculation with Classical Swine Fever Virus Provided a More Consistent Experimental Disease Model Compared to Oral Inoculation

## TL;DR

Intranasal infection with classical swine fever virus in pigs leads to more consistent disease outcomes compared to oral infection, improving experimental reliability.

## Contribution

The study shows that intranasal inoculation provides a more consistent model for studying classical swine fever in pigs.

## Key findings

- Intranasal inoculation resulted in direct infection of all pigs, while only two out of five were infected orally.
- Intranasally infected pigs showed more severe clinical disease and immune changes compared to orally infected pigs.
- Oral inoculation led to high variability, making it less suitable for comparative studies.

## Abstract

Classical swine fever is a serious virus infection in pigs, and outbreaks of the disease result in major problems with regard to animal welfare, as well as to the economy of the farmers. In order to control the disease, a lot of research has been carried out for decades. For classical swine fever, it has been demonstrated that the severity of the disease is determined by several factors, including virus strain and host factors, such as the age and immunity of the pigs. However, many studies have provided divergent results, making interpretation and conclusions difficult, so the putative influence of the experimental setup on the outcome of the infection has attracted increasing attention. For classical swine fever experimental studies, infection of the pigs is usually performed by the application of the virus in the mouth or the nose. In our study, we examined a number of parameters, including clinical disease and indicators of disease, in pigs infected orally or intranasally. The demonstrated wide variation in disease outcomes after oral application of the virus indicates that this method is less suitable for comparative studies. These observations provide additional information on the mechanisms of classical swine fever infection that are important for combatting the disease.

The severity of disease resulting from classical swine fever virus (CSFV) infection is determined by several factors, including virus strain and host factors. The different outcomes of experimental studies in pigs with the same strain of CSFV emphasize the need to elucidate the influence of individual factors within experimental protocols. In this study, we investigated the outcome of disease after oral and intranasal inoculation with a moderately virulent CSFV strain in young pigs. To compare the two routes of inoculation, various infection parameters were examined during a period of two weeks. While all intranasally inoculated pigs (n = 5) were directly infected, this was only the case for two out of five pigs after oral inoculation. In addition, the intranasally inoculated pigs developed a more pronounced clinical disease and pathological lesions, as well as markedly more change in hematological and immunological parameters than the orally inoculated pigs. The wide variation among the orally inoculated pigs implied that statistical evaluation was markedly impaired, leaving this route of application less suitable for comparative studies on classical swine fever. Furthermore, our study provides additional details about the immunomodulatory effects of CSFV on the kinetics of CRP, TNF-α, and leukocyte sub-populations in pigs after infection with the CSFV strain Paderborn.