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Title:   Author  item
                                            SANDBULTE, MATTHEW - Iowa State Universityitem
                                            PLATT, RATREE - Iowa State Universityitem
                                            ROTH, JAMES - Iowa State Universityitem
                                            HENNINGSON, JAMIE - Kansas State Universityitem
                                            GIBSON, KATHLEEN - Iowa State Universityitem
                                            RAJAO, DANIELA - Non ARS Employeeitem
                                            Loving, Crystalitem
                                            Baker, Amy
  Submitted to: Virology
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 6/10/2014
                                    Publication  Date: 7/17/2014
                                    Citation: Sandbulte, M.R., Platt, R., Roth, J.A., Henningson, J.N., Gibson, K.A., Rajao, D.S., Loving, C.L., Vincent, A.L. 2014. Divergent immune responses and disease outcomes in piglets immunized with inactivated and attenuated H3N2 swine influenza vaccines in the presence of maternally-derived antibodies. Virology. 464-465:45–54.Interpretive Summary: The study was designed to address questions about the effectiveness of two types of swine influenza virus vaccines, one using inactivated virus and one using attenuated live virus, to immunize piglets. We also tested whether the presence of maternal antibodies that the piglets received by suckling the sow interfered with vaccination.  Vaccinating growing pigs in the presence of maternal antibodies is a major problem for producers. The main finding of the study was that piglets with maternal antibodies had greatly reduced antibody immune responses to either vaccine. In the absence of maternal antibodies, the live vaccine induced superior responses compared to the inactivated vaccine in the respiratory tract. Vaccination with the live vaccine provided robust cross-protection and supports the concept that attenuated live swine influenza virus vaccines could be effective tools against infection with diverse strains of influenza virus, even when delivered to piglets possessing maternal antibody.
                                Technical Abstract: Vaccine-associated enhanced respiratory disease (VAERD) can occur in pigs immunized with whole-inactivated influenza virus (WIV) vaccine and subsequently infected with an antigenically divergent virus of the same HA subtype. Live-attenuated influenza virus (LAIV) vaccines administered intranasally have been shown to confer cross-protection under similar circumstances. An additional factor predisposing to VAERD in an H3N2 vaccine-challenge model was the presence of maternally-derived antibodies (MDA) at immunization. The current study was aimed at identifying immune correlates of VAERD versus heterologous protection. Piglets that acquired H3N2-specific MDA from immunized dams, along with seronegative controls, were vaccinated with WIV or intranasal LAIV and subsequently challenged with heterologous H3N2 influenza. WIV vaccination induced production of IgG that was detected in both the sera and lungs; however, MDA inhibited this response. Peripheral T cell responses were moderately induced following WIV vaccination, also with evidence of MDA inhibition. LAIV vaccine elicited mucosal antibodies and T cells reactive to both the vaccine and challenge strains. While the presence of MDA at LAIV vaccination inhibited mucosal antibody production, it did not interfere with T cell priming. Respiratory tract lesions and clinical disease were more pronounced in both WIV-vaccinated than non-vaccinated groups; however, MDA did not accentuate H3N2 VAERD above that of the WIV vaccination alone. LAIV was cross-protective even in MDA-positive LAIV-vaccinated pigs that had sharply reduced mucosal antibody responses following vaccination. Since T cell responses were not inhibited by MDA, cellular immunity likely had a significant role in LAIV-mediated cross-protection. Based on the data, a single dose LAIV vaccine can induce protection against heterologous challenge even in MDA-positive piglets. The model also offers insight into LAIV immunization of seropositive humans with limited humoral response to vaccine, supporting a role for T cells against seasonal antigenic variants.


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