Age at Vaccination and Timing of Infection Do Not Alter Vaccine-Associated Enhanced Respiratory Disease in Influenza A Virus-Infected Pigs

Souza, Carine K.; Rajão, Daniela S.; Loving, Crystal L.; Gauger, Phillip C.; Pérez, Daniel R.; Vincent, Amy L.

doi:10.1128/cvi.00563-15

Cited by 21 publications

(13 citation statements)

References 44 publications

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“…Pigs in study 1 were 3 weeks old when they received the first dose of the vaccine, while pigs in study 2 were 9 weeks old at the time of first vaccination. There is evidence that priming pigs at 4 weeks of age results in higher HI titers against the antigenically matched strains than priming at 9 weeks of age (36), consistent with our finding that pigs in study 1 developed higher HI titers than pigs in study 2. Despite the differences between the two studies presented here, there is a consistent pattern that the LAIV conferred efficient protection against antigenically matched and mismatched strains.…”

Section: Discussionsupporting

confidence: 89%

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Abente

Rajão

Santos

et al. 2018

J Virol

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Influenza A viruses in swine (IAV-S) circulating in the United States of America are phylogenetically and antigenically distinct. A human H3 hemagglutinin (HA) was introduced into the IAV-S gene pool in the late 1990s, sustained continued circulation, and evolved into five monophyletic genetic clades, H3 clades IV-A to -E, after 2009. Across these phylogenetic clades, distinct antigenic clusters were identified, with three clusters (cyan, red, and green antigenic cluster) among the most frequently detected antigenic phenotypes (Abente EJ, Santos J, Lewis NS, Gauger PC, Stratton J, et al. J Virol 90:8266-8280, 2016, https://doi.org/10.1128/JVI.01002-16). Although it was demonstrated that antigenic diversity of H3N2 IAV-S was associated with changes at a few amino acid positions in the head of the HA, the implications of this diversity for vaccine efficacy were not tested. Using antigenically representative H3N2 viruses, we compared whole inactivated virus (WIV) and live-attenuated influenza virus (LAIV) vaccines for protection against challenge with antigenically distinct H3N2 viruses in pigs. WIV provided partial protection against antigenically distinct viruses but did not prevent virus replication in the upper respiratory tract. In contrast, LAIV provided complete protection from disease and virus was not detected after challenge with antigenically distinct viruses. Due to the rapid evolution of the influenza A virus, vaccines require continuous strain updates. Additionally, the platform used to deliver the vaccine can have an impact on the breadth of protection. Currently, there are various vaccine platforms available to prevent influenza A virus infection in swine, and we experimentally tested two: adjuvanted-whole inactivated virus and live-attenuated virus. When challenged with an antigenically distinct virus, adjuvanted-whole inactivated virus provided partial protection, while live-attenuated virus provided effective protection. Additional strategies are required to broaden the protective properties of inactivated virus vaccines, given the dynamic antigenic landscape of cocirculating strains in North America, whereas live-attenuated vaccines may require less frequent strain updates, based on demonstrated cross-protection. Enhancing vaccine efficacy to control influenza infections in swine will help reduce the impact they have on swine production and reduce the risk of swine-to-human transmission.

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Section: Discussionsupporting

confidence: 89%

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Abente

Rajão

Santos

et al. 2018

J Virol

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“…Adjuvanted WIV vaccine was more immunogenic when administered to pigs at 4 and 7 weeks of age when compared to pigs vaccinated at 9 and 12 weeks of age as the number of IFN- SC and the amount of IFN- produced in recall assay was significantly increased in the 4/7 group compared to the NV group, while the 9/12 group was not statistically increased over NV group (Figure 4). In addition to the peripheral IFN- response reported here, serum hemagglutination-inhibition (HI) titers to vaccine antigen were greater in pigs vaccinated at 4 and 7 weeks-of-age versus 9 and 12 weeks-of-age (Souza et al, 2016).…”

Section: Discussionmentioning

confidence: 57%

“…Analysis of the cell type producing IFN- may provide insight into any skewing of immune response associated with vaccination at different ages, perhaps there's a difference in induction of CTL's versus doublepositive memory T cells that could provide mechanistic insight. Pigs would have likely been protected against homologous challenge given the antibody titers; however, vaccine associated enhanced respiratory disease (VAERD) occurred following challenge with the heterologous virus (Souza et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…In experiment 2 (EXP2), (Figures 2, 3, and 4), a total of 48 pigs were randomly assigned across one of five groups as they arrived off the truck from the farm. A group of pigs were vaccinated intramuscularly with 2 mL of WIV (MN08) formulated with adjuvant at 4 weeks of age and subsequently boosted at 7 weeks of age (4/7) or vaccinated at 9 weeks of age and subsequently boosted at 12 weeks of age (9/12) as described (Souza et al, 2016). Pigs in the LAIV group received LAIV as described above at 4 weeks and 7 weeks of age.…”

Section: Experimental Animals and Vaccinementioning

confidence: 99%

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Factors affecting induction of peripheral IFN-γ recall response to influenza A virus vaccination in pigs

Olson

Sandbulte

Souza

et al. 2017

Veterinary Immunology and Immunopathology

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While T cell contribution to IAV immunity is appreciated, data comparing methods to evaluate IFN-γ production by IAV-specific T cells elicited following vaccination is limited. To understand the differential immunogenicity between live-attenuated influenza virus (LAIV) and whole-inactivated virus (WIV) vaccines in relation to induction of peripheral T cell responses, ELISpot and ELISA were used to assess IFN-γ production by peripheral lymphocytes following antigen restimulation. Following restimulation, peripheral blood lymphocytes from WIV-vaccinated pigs had a greater quantity of IFN-γ secreting cells (SC) and IFN-γ secreted compared to LAIV vaccinated and non-vaccinated (NV) pigs. Pig age at time of WIV vaccination significantly impacted peripheral IAV-specific IFN-γ recall response, as did the inclusion of adjuvant in the WIV vaccine. Collectively, these data indicate that peripheral IAV-specific IFN-γ recall responses are not predictive of LAIV vaccination status, thus, are unlikely to be a useful surrogate for evaluating LAIV immunogenicity and predicting cross-protection. However, these data suggest that the evaluation of peripheral IFN-γ recall responses may be useful for identifying factors, such as animal age or vaccine formulation, that may impact parenterally-delivered WIV vaccine immunogenicity. Overall, results did not differ based upon the assay used to evaluate IFN-γ recall responses. Therefore, either ELISpot or ELISA could serve as a measure for evaluating IAV-specific IFN-γ cell-mediated immune responses in swine.

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“…However, epigraph vaccinated mice showed the lowest lung viral titers on day 3 post challenge as compared to the three other vaccine groups. Interestingly, although both epigraph and TX98 vaccination protected from weight loss, there were significantly higher lung viral titers in the TX98 vaccinated group, supporting that pathology does not always correlate with lung viral titer 26,27 .…”

Section: Interestingly T-cells From Epigraph Vaccinated Mice Recognimentioning

confidence: 92%

Epigraph Hemagglutinin Vaccine Induces Broad Cross-reactive Immunity Against Swine H3 Influenza Virus

Bullard

Corder

Korber

et al. 2020

Preprint

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Swine influenza virus (SIV) is a significant burden on the pork industry and threat to human health due to its zoonotic potential. Here, we utilized epigraph, a computational algorithm, to design a universal swine H3 (swH3) influenza vaccine. The epigraph hemagglutinin proteins were delivered using an Adenovirus type 5 vector and compared to a wild type hemagglutinin and the commercial inactivated vaccine, FluSure. In mice, epigraph vaccination led to significant cross-reactive antibody and T-cell responses against a diverse panel of swH3 isolates. Epigraph vaccination also reduced weight loss and lung viral titers in mice after challenge with three divergent swH3 viruses. Vaccination studies in swine, the target species for this vaccine, showed stronger levels of crossreactive antibodies and T-cell responses after immunization with epigraph vaccine compared to the wild type and FluSure vaccines. In both murine and swine models, epigraph vaccination showed superior cross-reactive immunity that should be further investigated as a universal swH3 vaccine.

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Age at Vaccination and Timing of Infection Do Not Alter Vaccine-Associated Enhanced Respiratory Disease in Influenza A Virus-Infected Pigs

Cited by 21 publications

References 44 publications

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Comparison of Adjuvanted-Whole Inactivated Virus and Live-Attenuated Virus Vaccines against Challenge with Contemporary, Antigenically Distinct H3N2 Influenza A Viruses

Factors affecting induction of peripheral IFN-γ recall response to influenza A virus vaccination in pigs

Epigraph Hemagglutinin Vaccine Induces Broad Cross-reactive Immunity Against Swine H3 Influenza Virus

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