Comparison of humoral and cellular immune responses to inactivated swine influenza virus vaccine in weaned pigs

Platt, Ratree; Vincent, Amy L.; Gauger, Phillip C.; Loving, Crystal L.; Zanella, Eraldo Lourenso; Lager, Kelly M.; Kehrli, Marcus E.; Kimura, Kiyomi; Roth, James A.

doi:10.1016/j.vetimm.2011.05.005

Cited by 23 publications

(26 citation statements)

References 27 publications

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“…An influenza-specific, cross-reactive CD4 + CD8 + memory T cell population was detected in MN08 vaccine-primed pigs prior to challenge and reported previously by our group (28). In the same study, a significant increase in cross-reactive CD8 + T-cells was detected by flow cytometry in the V/C pigs post ex vivo stimulation with H1N1pdm09, suggesting CD8 + T-cells were primed by the inactivated vaccine (28). may be responsible for damage to infected tissue as a consequence of viral clearance, as previously reported (2).…”

supporting

confidence: 82%

“…This cytokine profile suggests T cell priming in the immunized pigs, and is consistent with the presence of IL-2 and IFN-c secreting CD4 + CD8 + memory T cells in swine (3) and with the rapid increase in total antibody against the heterologous challenge virus in the vaccine primed pigs. An influenza-specific, cross-reactive CD4 + CD8 + memory T cell population was detected in MN08 vaccine-primed pigs prior to challenge and reported previously by our group (28). In the same study, a significant increase in cross-reactive CD8 + T-cells was detected by flow cytometry in the V/C pigs post ex vivo stimulation with H1N1pdm09, suggesting CD8 + T-cells were primed by the inactivated vaccine (28).…”

supporting

confidence: 81%

“…All cytokines were significantly higher ( p < 0.05) at 5 dpi (necropsy) in the vaccine-primed pigs who demonstrated VAERD. Additionally, V/C pigs demonstrated significantly higher ( p < 0.05) IFN-c levels compared to the other two groups at 1 and 2 dpi, suggesting prior vaccination may have resulted in the induction of memory T cells as previously described in MN08-vaccinated pigs and T cell activation upon challenge (28). However, elevated IL-10 may be a response by the host to inhibit pro-inflammatory cytokine production, IFNc, or natural killer cells that may be contributing to the immunopathology described in VAERDaffected pigs (6,24).…”

Section: Serum and Lung Igg Whole Virus Anti-mn08 And Cross-reactive supporting

confidence: 58%

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Vaccine-Associated Enhanced Respiratory Disease Does Not Interfere with the Adaptive Immune Response Following Challenge with Pandemic A/H1N1 2009

et al. 2013

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The implications of sequential prime and challenge with mismatched influenza A viruses is a concern in mammals, including humans. We evaluated the ability of pigs affected with vaccine-associated enhanced respiratory disease (VAERD) to generate a humoral immune response against the heterologous challenge virus inciting the VAERD. Vaccinated and challenged (V/C) pigs were administered an inactivated swine δ-cluster H1N2 (MN08) vaccine with an HA similar to pre-2009 seasonal human viruses and challenged with heterologous A(H1N1) pandemic 2009 (H1N1pdm09). Vaccination induced MN08-specific hemagglutination inhibition (HI) antibody but not cross-reacting H1N1pdm09 HI antibody. However, vaccinated pigs demonstrated significantly higher post-challenge anti-H1N1pdm09 serum neutralizing (SN) antibodies at 14 and 21 days post inoculation (dpi) compared to nonvaccinated, challenged pigs (NV/C), indicating a priming effect of the vaccine. Serum and lung whole virus anti-H1N1pdm09 IgG ELISA antibodies in the vaccinated group were significantly higher than the challenge only pigs at all-time points evaluated. Lung IgA ELISA antibodies to both antigens were detected at 2, 5, and 21 dpi in vaccine-primed pigs, contrasted against mucosal ELISA antibody responses detected only at 21 dpi in the naïve-challenged group. Collectively, vaccine-primed pigs demonstrated a robust humoral immune response and elevated local adaptive cytokine levels, indicating VAERD does not adversely affect the induction of an immune response to challenge with heterologous virus despite the severe clinical disease and underlying lung pathology. Thus, original antigenic sin does not appear to be a component of VAERD. RightsWorks produced by employees of the U.S. Government as part of their official duties are not copyrighted within the U.S. The content of this document is not copyrighted. AuthorsPhillip Charles Gauger, Crystal Lynn Loving, Kelly M. Lager, Bruce H. Janke, Marcus E. Kehrli Jr., James A. The implications of sequential prime and challenge with mismatched influenza A viruses is a concern in mammals, including humans. We evaluated the ability of pigs affected with vaccine-associated enhanced respiratory disease (VAERD) to generate a humoral immune response against the heterologous challenge virus inciting the VAERD. IgG ELISA antibodies in the vaccinated group were significantly higher than the challenge only pigs at all-time points evaluated. Lung IgA ELISA antibodies to both antigens were detected at 2, 5, and 21 dpi in vaccine-primed pigs, contrasted against mucosal ELISA antibody responses detected only at 21 dpi in the naïve-challenged group. Collectively, vaccine-primed pigs demonstrated a robust humoral immune response and elevated local adaptive cytokine levels, indicating VAERD does not adversely affect the induction of an immune response to challenge with heterologous virus despite the severe clinical disease and underlying lung pathology. Thus, original antigenic sin does not appear to be a component of VAERD.

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supporting

confidence: 82%

supporting

confidence: 81%

Section: Serum and Lung Igg Whole Virus Anti-mn08 And Cross-reactive supporting

confidence: 58%

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Vaccine-Associated Enhanced Respiratory Disease Does Not Interfere with the Adaptive Immune Response Following Challenge with Pandemic A/H1N1 2009

et al. 2013

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“…Although cell-mediated immunity also correlates with the rate of viral clearance and protection of the respiratory tract after challenge with infectious influenza viruses [8], cellular-mediated immune responses have not been assessed following vaccination with the A(H1N1)pdm/09 vaccines and only limited data is available on the cellular-mediated immune responses elicited by influenza vaccines in general [9].…”

Section: Introductionmentioning

confidence: 99%

Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

et al. 2012

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Following the emergence and global spread of a novel H1N1 influenza virus in 2009, two A(H1N1)pdm/09 influenza vaccines produced from the A/California/07/09 H1N1 strain were selected and used for the national immunisation programme in the United Kingdom: an adjuvanted split virion vaccine and a non-adjuvanted whole virion vaccine. In this study, we assessed the immune responses generated in inbred large white pigs (Babraham line) following vaccination with these vaccines and after challenge with A(H1N1)pdm/09 virus three months post-vaccination. Both vaccines elicited strong antibody responses, which included high levels of influenza-specific IgG1 and haemagglutination inhibition titres to H1 virus. Immunisation with the adjuvanted split vaccine induced significantly higher interferon gamma production, increased frequency of interferon gamma-producing cells and proliferation of CD4 − CD8 + (cytotoxic) and CD4 + CD8 + (helper) T cells, after in vitro re-stimulation. Despite significant differences in the magnitude and breadth of immune responses in the two vaccinated and mock treated groups, similar quantities of viral RNA were detected from the nasal cavity in all pigs after live virus challenge. The present study provides support for the use of the pig as a valid experimental model for influenza infections in humans, including the assessment of protective efficacy of therapeutic interventions.

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“…Peripheral blood mononuclear cells (PBMC) were isolated and tested for activation markers by MP-FCM after in vitro stimulation with both challenge viruses, using a previously described method (Platt et al, 2011). Briefly, PBMC of each pig were incubated with either RPMI 1640 media (Mediatech, Inc., Herndon, VA) as non-antigen stimulation control, ConA at 5 μg/ml as mitogen control, undiluted conditioned media from uninfected MDCK culture as mock-stimulation control, or one of the challenge viruses (H1N2-δ1(1:7) or H1N1pdm09(2:6)) as recall antigens in duplicate.…”

Section: Methodsmentioning

confidence: 99%

Heterologous challenge in the presence of maternally-derived antibodies results in vaccine-associated enhanced respiratory disease in weaned piglets

et al. 2016

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Control of influenza A virus (IAV) in pigs is done by vaccination of females to provide maternally-derived antibodies (MDA) through colostrum. Our aim was to evaluate if MDA interfere with IAV infection, clinical disease, and transmission in non-vaccinated piglets. In a first study, naïve sows were vaccinated with H1N2-δ1 whole inactivated virus (WIV) vaccine. In a follow-up study seropositive sows to 2009 pandemic H1N1 (H1N1pdm09) were boosted with H1N1pdm09 WIV or secondary experimental infection (EXP). MDA-positive pigs were challenged with homologous or heterologous virus, and MDA-negative control groups were included. WIV-MDA piglets were protected from homologous infection. However, piglets with WIV-derived MDA subsequently challenged with heterologous virus developed vaccine associated enhanced respiratory disease (VAERD), regardless of history of natural exposure in the sows. Our data indicates that although high titers of vaccine-derived MDA reduced homologous virus infection, transmission, and disease, MDA alone was sufficient to induce VAERD upon heterologous infection.

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Comparison of humoral and cellular immune responses to inactivated swine influenza virus vaccine in weaned pigs

Cited by 23 publications

References 27 publications

Vaccine-Associated Enhanced Respiratory Disease Does Not Interfere with the Adaptive Immune Response Following Challenge with Pandemic A/H1N1 2009

Vaccine-Associated Enhanced Respiratory Disease Does Not Interfere with the Adaptive Immune Response Following Challenge with Pandemic A/H1N1 2009

Immune Responses in Pigs Vaccinated with Adjuvanted and Non-Adjuvanted A(H1N1)pdm/09 Influenza Vaccines Used in Human Immunization Programmes

Heterologous challenge in the presence of maternally-derived antibodies results in vaccine-associated enhanced respiratory disease in weaned piglets

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