Abstract
Swine influenza is a highly contagious acute viral disease of the respiratory tract in pigs, which is prevalent world-wide. The disease causes considerable economic damage primarily due to reduced weight gain in finishing pigs and reduced reproductive performance of sows. In addition, influenza is a zoonotic disease, because swine influenza
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viruses can transmit to, and cause disease in people, and pigs can be a source of new human influenza strains. Moreover, antigenic drift of the swine influenza A H3N2 viruses in the Netherlands and Belgium was demonstrated and a replacement of this strain by a more recent swine H3N2 virus in swine vaccines has been recommended. In this thesis, research is described in which the protection conferred by current swine influenza vaccines was evaluated and possible improvements to influenza vaccines were studied.
A current commercial split virus in oil adjuvant vaccine was shown to be efficacious in protecting pigs against a drift variant of H3N2 in a vaccination-challenge experiment. Therefore, there does not yet seem to be an urgent need for the virus strains to be replaced by more recent strains. The swine vaccine may confer a broader protection than human sub-unit vaccines possibly because of the presence of the other viral proteins in addition to the HA and NA, and of the adjuvant. Because the variability of the HA and NA are a major problem in vaccinating pigs and humans against influenza, immune responses to other more conserved proteins were studied. Antibodies to the highly conserved extracellular domain of M2 and cytotoxic T cells (CTL) to the NP seemed to be involved in broad-spectrum protection in pigs after infection, but are not induced by current vaccines. However, an experimental vaccine that induced those effectors, and no antibodies to the HA and NA, enhanced instead of prevented clinical signs after viral challenge. This indicates that those effectors can even exacerbate disease, when induced parenterally and/or if other effectors are absent. Therefore, although including conserved antigens in vaccines and enhancing the response against them could broaden protection, caution must be exercised to make sure they do not enhance disease after vaccination with novel generations of vaccines. Successive intranasal vaccination with an attenuated H1N1 strain and an H3N2 strain will specifically induce mucosal subtype cross-reactive IgA and IgG antibodies, as well as CTL. Although such drastic vaccination strategies are not applicable to pigs they might be applied as a strategy of immunisation in case a next human pandemic is feared. A broad-spectrum vaccine, which can be applied intramuscular would be ideal but as long as such a vaccine cannot be developed, extensive influenza surveillance and regular updating of vaccine strains will remain necessary.
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