Maternal derived antibodies induce vaccine-associated enhanced respiratory disease in weaned pigs challenged with heterologous virus

Authors: RAJAO, DANIELA - Non ARS Employee; Baker, Amy; Loving, Crystal; GAUGER, PHILIP - Iowa State University; SANDBULTE, MATTHEW - Iowa State University; Kitikoon, Pravina

Submitted to: American Association of Swine Veterinarians Annual Meeting
Publication Type: Proceedings
Publication Acceptance Date: 9/3/2013
Publication Date: 3/1/2014
Citation: Rajao, D., Vincent, A.L., Loving, C.L., Gauger, P.C., Sandbulte, M., Kitikoon, P. 2014. Maternal derived antibodies induce vaccine-associated enhanced respiratory disease in weaned pigs challenged with heterologous virus. Proceedings of 45th American Association of Swine Veterinarians Annual Meeting. p. 51-54.

Interpretive Summary:

Technical Abstract: Introduction Effective vaccine immunization against influenza A viruses (IAV) in pigs in the United States is a challenge because of the great antigenic diversity of co-circulating viruses. Another obstacle to vaccine efficacy in pigs is the presence of maternally derived antibodies (MDA), which have been shown to lead to vaccine-enhanced respiratory disease (VAERD) when pigs are vaccinated in the presence of MDA.1 The aim of this study was to evaluate the effect of MDA on IAV infection, clinical disease, and transmission in weaned non-vaccinated piglets, and if MDA alone could lead to VAERD. Materials and methods Sows with existing antibodies to 2009 pandemic H1N1 (H1N1pdm09) from natural exposure were vaccinated with 3 doses of H1N1pdm09 whole inactivated virus (WIV) or live attenuated influenza virus (LAIV) vaccines. Identical H1N1pdm09 viruses were used for both vaccines as previously described,2 with the WIV virus subjected to UV inactivation and combined with adjuvant (Emulsigen D, MVP Labs). The litters from vaccinated sows were tested for the presence of IAV-specific antibodies, weaned at 2 weeks of age and used for the MDA groups (n=8 per challenge group; n=3 for negative control group). Nineteen two-week-old crossbred healthy pigs from a high-health herd free of IAV and PRRSV were used as controls without MDA (n=8 per challenge group; n=3 for negative control group). At 3 weeks of age, piglets were challenged with 2 ml intratracheally and 1 ml intranasally of 1 × 105 TCID50/ml of either homologous A/CA/04/09 H1N1pdm09 or heterologous A/SW/MN/02011/08 H1N2 d1 (d1-H1N2) viruses. At 2 days post-infection (dpi), thirty MDA-negative pigs (n=5 per group) obtained from the same source as the controls were placed in separate raised decks in the same room as each inoculated group to evaluate indirect contact transmission. Primary infected pigs were observed daily for clinical signs of respiratory disease and rectal temperatures were measured at 1 to 5 dpi. Nasal swabs were taken from primary pigs on 1 to 5 dpi and from indirect contact pigs on 1 to 5, 7, 9, and 11 days post contact (dpc) for virus isolation as previously described.3 Serum was collected before challenge and at 5 dpi or 15 dpc, and tested for IAV antibodies by hemagglutination inhibition (HI), isotype specific ELISA, and serum neutralization assays.1,3,4 Primary pigs were humanely euthanized and necropsied at 5 dpi for macroscopic lesion evaluation and collection of bronchoalveolar lavage fluid (BALF) and trachea and lung tissue. BALF was tested by virus isolation.3 Lungs and trachea tissue sections were scored for microscopic lesions.3 Indirect contact pigs were euthanized at 15 dpc. Results were analyzed using analysis of variance (ANOVA), with P = 0.05 considered significant. Results and discussion Both LAIV and WIV vaccines given to sows resulted in efficient transfer of MDA, but challenge with homologous and heterologous viruses led to very distinct outcomes depending on the source of MDA. All MDA-positive pigs had high levels of neutralizing anti-H1N1pdm09 antibodies prior to challenge by both HI and neutralization assays (Figure 1A,B). Serum IgG titers were also elevated for pigs with either type of MDA (Figure 2A); however, cross-reacting IgG to the heterologous d1-H1N2 virus was only observed in the WIV-MDA groups (Figure 2B). Challenge with H1N1pdm09 resulted in mild lethargy in MDA-negative pigs whereas pigs with homologous MDA had no apparent clinical signs. WIV-MDA piglets were protected from homologous infection with H1N1pdm09, as macroscopic lung lesions and trachea microscopic lesions were not different from the non-infected pigs (Table 1) and no virus was detected in their lungs at 5 dpi (Table 2). Only one pig in this group shed low titers of virus after challenge (Table 2), and did not result in transmission to indirect contact pigs. LAIV-MDA r