Pre-registration efficacy study of a novel marker vaccine against classical swine fever on maternally derived antibody positive (MDA+) target animals.

Maternally Derived Antibodies (MDA) can have a negative effect on the efficacy of live attenuated vaccines against classical swine fever (CSF). For this reason, a marker vaccine candidate CP7_E2alf was tested for its efficacy in the presence of MDA. Pregnant sows were vaccinated four weeks before farrowing with CSF virus (CSFV) strain "Thiverval". A total of 40 piglets with MDAs were included in this study. At six weeks of age the piglets were allocated into three treatment groups using generalized randomized block design (GRBD) blocking on serological status and pen location. Of the 40 piglets with MDAs, 30 piglets were vaccinated either orally (n = 15) or intramuscularly (n = 15) with a single dose of vaccine candidate produced under Good Laboratory Practice (GLP) conditions. The ten remaining piglets were allocated into the untreated control group. All 40 piglets were oronasally challenged with 2 ml of the highly virulent CSFV strain "Koslov" 14 days after vaccination. It was revealed that presence of MDAs negatively influences the efficacy of the live marker vaccine candidate, however, the extent of this negative impact depends on the route of vaccine administration. Based on our observations, intramuscular vaccination is recommended during CSF control programs in order to develop superior immune protection.

Pre-registration efficacy study of a novel marker vaccine against classical swine fever on Maternally Derived Antibody negative (MDA-) target animals.

Classical swine fever (CSF) marker vaccine candidate CP7_E2alf produced under Good Laboratory Practice (GLP) conditions by Pfizer was tested on 40 six-week-old MDA-piglets according to the European Pharmacopoeia (Ph.Eur.) requirements. Single doses of CP7_E2alf were given to 15 piglets orally, while 15 other piglets were intramuscularly vaccinated. Ten additional animals were included as unvaccinated controls. All piglets were oronasally challenged with the highly virulent CSF virus (CSFV) strain "Koslov" 14 days after vaccination. CP7_E2alf administered i.m. provided a complete protection, while p.o. administratrion triggered only partial protection. The level of protection was determined by the development of clinical signs, viraemia and rate of mortality. The vaccine candidate met the criteria of Ph. Eur Monograph 0065, "Swine-fever vaccine (live, prepared in cell cultures), classical" 7th Edition, which claims the efficacy test is invalid if fewer than 50 per cent of the control piglets display typical signs of serious infection of CSF or die, and if fewer than 100 per cent of the control piglets show clinical signs of disease within 21 days following challenge. Fulfilling these validity criteria is a key step in the registration procedure for a vaccine candidate to become openly available.

Cytokine and immunoglobulin isotype profiles during CP7_E2alf vaccination against a challenge with the highly virulent Koslov strain of classical swine fever virus.

CP7_E2alf is a promising marker vaccine candidate against classical swine fever (CSF). To better understand the mechanisms of protection, cytokine and isotype-specific antibody profiles were investigated in CP7_E2alf vaccinated pigs before and after challenge with the highly virulent CSFV strain "Koslov" at 14 days or 6 months post-vaccination. The interference of vaccination with CSFV pathogeny-related cytokine responses, previously described following a moderately virulent challenge, was confirmed. However, the levels of additional cytokines, TNF-α and IL-6, were significantly attenuated by vaccination following highly virulent challenge. This vaccine interference with cytokine response was not dependent on the immunization route or the consequence of competition between vaccine and challenge strain. Interestingly, IFN-γ enhancement and persistent high IgG2 levels suggested an important role of cell-mediated immunity in long-term protection against CSFV induced by CP7_E2alf vaccination. IgA production also revealed a stimulation of mucosal immunity, especially after oral administration of the vaccine.