Immune Responses to Avian Influenza Viruses

Koutsakos, Marios; Kedzierska, Katherine; Subbarao, Kanta

doi:10.4049/jimmunol.1801070

Cited by 56 publications

(52 citation statements)

References 118 publications

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“…Aberrant pulmonary immune responses correlate with the pathogenesis of multiple human respiratory viral infections, including IAV infection [1]. Immune responses in the lung tissue include both antiviral and inflammatory factors, which play crucial roles in host protection and immunopathogenesis [2,3]. Through the integrated action of different pro-inflammatory factors, different immune cells are recruited into the airway.…”

Section: Introductionmentioning

confidence: 99%

Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis

Zhang

Yuan

et al. 2020

PLoS Pathog

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Influenza A virus (IAV) infection is a complicated process. After IAVs spread to the lung, extensive pro-inflammatory cytokines and chemokines are released, which largely determine the outcome of infection. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of more than 16,000 immune cells in the pulmonary tissue of infected mice, and demonstrated that two waves of proinflammatory factors were released. A group of IAV-infected PD-L1 + neutrophils were the major contributor to the first wave at an earlier stage (day 1-3 post infection). Notably, at a later stage (day 7 post infection) when IAV was hardly detected in the immune cells, a group of platelet factor 4-positive (Pf4 +)-macrophages generated another wave of pro-inflammatory factors, which were probably the precursors of alveolar macrophages (AMs). Furthermore, single-cell signaling map identified inter-lineage crosstalk between different clusters and helped better understand the signature of PD-L1 + neutrophils and Pf4 +-macrophages. Our data characteristically clarified the infiltrated immune cells and their production of proinflammatory factors during the immunopathogenesis development, and deciphered the important mechanisms underlying IAV-driven inflammatory reactions in the lung.

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Section: Introductionmentioning

confidence: 99%

Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis

Zhang

Yuan

et al. 2020

PLoS Pathog

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“…To address these questions, we hypothesized that a new platform for manufacturing influenza vaccines based on yeast surface display technology could provide potential of protective immunity. In the present study, HA was chosen as a model antigen for influenza vaccine development because of that HA of influenza H7N9 virus has strong immunogenicity and neutralizing activity [1,6,17]. Thus, we generated HA protein of A/Anhui/1/2013 (AH-H7N9) virus was displayed on the surface of S.cerevisiae EBY100 (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…The candidate vaccine strains must be further selected based on their high growth capability in eggs and high yield of HA content before they can be used for production of vaccines. In this case, manufacturing problems experienced in recent years illustrate that the current methods of production are fragile in ensuing an adequate and timely supply of influenza vaccine [6]. More importantly, the egg-based technology may not be suitable to respond to a pandemic crisis.…”

Section: Introductionmentioning

confidence: 99%

Yeast display platform technology to prepare oral vaccine against lethal H7N9 virus challenge in mice

et al. 2020

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Background: Existing methods for preparing influenza vaccines pose the greatest challenge against highly pandemic avian influenza H7N9 outbreak in the poultry and humans. Exploring a new strategy for manufacturing and delivering a safe and effective H7N9 vaccine is needed urgently. Results: An alternative approach is to develop an influenza H7N9 oral vaccine based on yeast display technology in a timely manner. Hemagglutinin (HA) of A/Anhui/1/2013 (AH-H7N9) is used as a model antigen and characterized its expression on the surface of Saccharomyces cerevisiae (S.cerevisiae) EBY 100. Mice administrated orally with S.cerevisiae EBY100/pYD5-HA produced significant titers of IgG antibody as well as significant amounts of cytokines IFN-γ and IL-4. Importantly, S.cerevisiae EBY100/pYD5-HA could provide effective immune protection against homologous A/ Anhui/1/2013 (AH-H7N9) virus challenge. Conclusions: Our findings suggest that platform based on yeast surface technology provides an alternative approach to prepare a promising influenza H7N9 oral vaccine candidate that can significantly shorten the preparedness period and result in effective protection against influenza A pandemic.

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“…The HA1 subunit, which forms the globular head, is highly variable among subtypes and contains major neutralizing epitopes. The HA2 subunit, which forms most of the stalk domain, is considerably conserved among subtypes and contains few but cross-reactive neutralizing epitopes (Palese and Shaw, 2013;Kirkpatrick et al, 2018;Koutsakos et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Contributions of HA1 and HA2 Subunits of Highly Pathogenic Avian Influenza Virus in Induction of Neutralizing Antibodies and Protection in Chickens

et al. 2020

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Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes a devastating disease in poultry. Vaccination is an effective method of controlling avian influenza virus (AIV) infection in poultry. The hemagglutinin (HA) protein is the major determinant recognized by the immune system of the host. Cleavage of the HA precursor HA0 into HA1 and HA2 subunits is required for infectivity of the AIV. We evaluated the individual contributions of HA1 and HA2 subunits to the induction of HPAIV serum neutralizing antibodies and protective immunity in chickens. Using reverse genetics, recombinant Newcastle disease viruses (rNDVs) were generated, each expressing HA1, HA2, or HA protein of H5N1 HPAIV. Chickens were immunized with rNDVs expressing HA1, HA2, or HA. Immunization with HA induced high titers of serum neutralizing antibodies and prevented death following challenge. Immunization with HA1 or HA2 alone neither induced serum neutralizing antibodies nor prevented death following challenge. Our results suggest that interaction of HA1 and HA2 subunits is necessary for the display of epitopes on HA protein involved in the induction of neutralizing antibodies and protection. These epitopes are lost when the two subunits are separated. Therefore, vaccination with either a HA1 or HA2 subunit may not provide protection against HPAIV.

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Immune Responses to Avian Influenza Viruses

Cited by 56 publications

References 118 publications

Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis

Two waves of pro-inflammatory factors are released during the influenza A virus (IAV)-driven pulmonary immunopathogenesis

Yeast display platform technology to prepare oral vaccine against lethal H7N9 virus challenge in mice

Contributions of HA1 and HA2 Subunits of Highly Pathogenic Avian Influenza Virus in Induction of Neutralizing Antibodies and Protection in Chickens

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