The host response to virus infection begins almost immediately with recognition of virus by host cells leading to the production of antiviral substances such as interferons. One interferon, interferon alpha (IFNα), plays a significant role in the antiviral immune response by stimulating the production of an antiviral state that inhibits viral replication in the host cells. In addition, IFNα plays a role in stimulating the adaptive immune response which is responsible for clearing the virus and preventing future infections. Compared to other viruses that infect the respiratory tract, such as swine influenza virus, porcine reproductive and respiratory virus (PRRSV) appears to induce little IFNα production in the pig. This might be one reason for the persistence of PRRSV in the host and the inadequate immune response to the virus and vaccines. Thus if we could increase the amount of IFNα present during PRRSV infection we may be able to inhibit the virus from replicating, causing disease, and spreading as well as improve the immune response to vaccination to prevent future infections. The objectives of this project were to 1) determine whether IFNα could be used as an adjuvant (a substance that enhances the body’s immune response to a vaccine) with attenuated PRRSV vaccine; and 2) determine the effectiveness of metaphylactic use of IFNα during an outbreak of PRRSV. Metaphylactic use is defined as the timely mass medication of a group of animals to eliminate or minimize an outbreak of disease.
For objective 1, pigs were divided into 4 groups and given the following treatments: Group 1 received Ingelvac PRRS ATP vaccine only, group 2 received IFNα and Ingelvac PRRS ATP vaccine, group 3 received IFNα only, and group 4 did not receive either vaccine or IFNα for comparison. After vaccination blood was collected for virus detection and immune assays. The pigs in group 1, which were given the vaccine only, replicated the virus and developed a typical immune response to PRRSV vaccine. Conversely, no virus was recovered from the pigs in group 2 (given the vaccine with IFNα) after vaccination and these pigs did not seroconvert or develop an immune response after vaccination. Originally the pigs in groups 1-3 were to be challenged with PRRSV after vaccination to determine which group was best protected. Since the vaccine virus did not appear to replicate in pigs in group 2 and no measurable immune response was detected, the experimental design was changed and all pigs in groups 1-3 were given a second dose of the vaccine to determine if there would be a boost in the response to the vaccine in either group 1 or 2. The pigs in group 1 that had initially replicated the vaccine virus and developed an immune response did not respond to the second dose of vaccine. Pigs in group 2 and 3 responded in a similar manner replicating and developing an immune response to the subsequent dose of vaccine virus demonstrating again that the pigs in group 2 behaved like naïve pigs that had never been exposed to vaccine. Although the presence of IFNα did not prove useful as an adjuvant when given simultaneously with a PRRSV attenuated vaccine under the conditions of this study, the results demonstrating the total inhibition of replication and transmission of the vaccine virus provides further evidence that IFNα has potential for metaphylactic use during an outbreak of PRRSV. It is possible that if the timing of administration of the IFNα is altered, perhaps if it were to be administered a day or two after the vaccine allowing an initial time for replication, or if the vaccine was administered intranasally, it would have the more desired adjuvant effect.
The second objective, determining the effectiveness of metaphylactic use of IFNα has yet to be completed. This experiment will consist of groups of pigs that consisted of both primary PRRSV infected pigs as well as contacts that will be treated with various combinations of IFNα. This experiment will mimic the early phases of an outbreak of PRRSV where some pigs in the herd have already been infected (primary challenged pigs) and some have yet to be exposed (contacts) and will examine the effectiveness of treatment with IFNα on controlling viral replication and disease, as well as transmission during an outbreak. The experiment will consist of pigs that are divided into 4 groups with seeder (directly infected) pigs and contact pigs. The seeders will be challenged with PRRSV. Twenty-four hours after challenge, contacts will be comingled with seeders. In group 1 neither seeders nor contacts will be treated with IFNα, in group 2 only seeders will be treated with IFNα but not contacts, in group 3 only contacts will be treated with IFNα and not seeders, and in group 4 both seeders and contacts will be treated with IFNα. IFNα will be given at the time of comingling and again 3 days later. Samples will be taken from both seeders and contacts to determine if the pigs replicate the virus, transmit the virus and develop an immune response to the virus. In previous experiments, we have shown that with one dose of IFNα pigs challenged with PRRSV had lower febrile responses, decreased lung lesions, delayed virus replication and decrease viral load in the sera. The results of the first objective demonstrating that IFNα can totally inhibit viral replication and transmission of a vaccine strain of PRRSV and preliminary data we have generated thus far indicates that IFNα may be very effective at minimizing disease impact and spread of PRRSV, one of the most devastating and costly diseases to the swine industry.
Susan L. Brockmeier, DVM, PhD
Research Veterinary Medical Officer
USDA-ARS-National Animal Disease Center
Building 20, Room 2529
1920 Dayton Avenue
Ames, IA 50010