Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs

Feest, Katherine; McNee, Adam; Manjegowda, Tanuja; Carr, B. Veronica; Paudyal, Basudev; Chrun, Tiphany; Maze, Emmanuel A.; Mccarron, Amy; Morris, Susan; Everett, Helen; MacLoughlin, Ronan; Salguero, Francisco J.; Lambe, Teresa; Gilbert, Sarah C.; Tchilian, Elma

doi:10.1038/s41541-023-00620-2

Cited by 13 publications

(8 citation statements)

References 50 publications

(53 reference statements)

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“…Additionally, pigs exhibit a comparable distribution of sialic acid receptors in the respiratory tract (38). We have established a robust influenza challenge pig model to study immunity to influenza and evaluate the efficacy of novel vaccines and therapeutics (39)(40)(41)(42). We have further shown that pig immune responses following infection with H1N1pdm09 influenza virus are similar to those induced in humans (43).…”

Section: Introductionmentioning

confidence: 94%

Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunisation in the pig lung

Muir,

Paudyal,

Schmidt

et al. 2023

Preprint

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The pig is a natural host for influenza viruses and integrally involved in virus evolution through interspecies transmissions between humans and swine. Swine have many physiological, anatomical, and immunological similarities to humans, and are an excellent model for human influenza. Here, we employed single RNA-sequencing (scRNA-seq) and flow cytometry to characterize the major leucocyte subsets in bronchoalveolar lavage (BAL), twenty-one days after H1N1pdm09 infection or respiratory immunization with an adenoviral vector vaccine expressing haemagglutinin and nucleoprotein with or without IL-1β. Mapping scRNA-seq clusters from BAL onto those previously described in peripheral blood facilitated annotation and highlighted differences between tissue resident and circulating immune cells. ScRNA-seq data and functional assays revealed lasting impacts of immune challenge on BAL populations. First, mucosal administration of IL-1β reduced the number of functionally active Treg. Second, influenza infection upregulated IFI6 in BAL cells, decreasing their susceptibility to virus replicationin vitro. Our data provides a reference map of porcine BAL cells and reveals lasting immunological consequences of influenza infection and respiratory immunisation in a highly relevant large animal model for respiratory virus infection.Author SummaryPigs and humans have a similar anatomy and physiology. In humans, cells from lung-washes are used to study immune responses and it was shown that these cells are crucial in protection against respiratory diseases such as influenza and COVID-19. To better understand lung immunity, we compared genes expressed in cells of pig lung-wash to white blood cells, providing an atlas for future studies of immunity in the lung. We also tested a vaccine given to the lung containing IL-1β, a strong immune activator that protects mice against influenza virus infection. However, although IL-1β increased pig immune responses it did not protect pigs against infection. We also showed that the number of immune cells that dampen immune responses (regulatory T cells) is reduced. In addition, we demonstrated increased expression of a protein, IFI6, 21 days after infection showing that while immune cells in the lung have common properties, the invading organisms influence them significantly. Our study elucidates why some vaccines fail despite inducing powerful immune responses, emphasizes the need for caution when applying results from small animals like mice to humans, and indicates the importance of the pig as a model to study disease in humans and livestock.

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Section: Introductionmentioning

confidence: 94%

Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunisation in the pig lung

Muir,

Paudyal,

Schmidt

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…In contrast, local IgA and IgG can be detected as early as 4-5 days after IAV-S infection ( Lee et al., 1995 ; Larsen et al., 2000 ). Recent research correlated local and systemic antibodies elicited after different routes of immunization in pigs and observed that either local or systemic neutralizing antibody responses can provide protection against IAV-S infection ( Vatzia et al., 2023 ). Cross-protective antibody responses against genetically divergent HA proteins are dictated by the overall genetic similarly of the HA protein and how well the targeted epitopes match ( Reeth et al., 2004 ; Kreijtz et al., 2011 ).…”

Section: Current Challenges In Developing a Universal Iav-s Vaccinementioning

confidence: 99%

Swine influenza A virus: challenges and novel vaccine strategies

Petro-Turnquist,

Pekarek,

Weaver

2024

Front. Cell. Infect. Microbiol.

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Swine Influenza A Virus (IAV-S) imposes a significant impact on the pork industry and has been deemed a significant threat to global public health due to its zoonotic potential. The most effective method of preventing IAV-S is vaccination. While there are tremendous efforts to control and prevent IAV-S in vulnerable swine populations, there are considerable challenges in developing a broadly protective vaccine against IAV-S. These challenges include the consistent diversification of IAV-S, increasing the strength and breadth of adaptive immune responses elicited by vaccination, interfering maternal antibody responses, and the induction of vaccine-associated enhanced respiratory disease after vaccination. Current vaccination strategies are often not updated frequently enough to address the continuously evolving nature of IAV-S, fail to induce broadly cross-reactive responses, are susceptible to interference, may enhance respiratory disease, and can be expensive to produce. Here, we review the challenges and current status of universal IAV-S vaccine research. We also detail the current standard of licensed vaccines and their limitations in the field. Finally, we review recently described novel vaccines and vaccine platforms that may improve upon current methods of IAV-S control.

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“…injection evoked systemic antibody responses, while aerosol immunization led to mucosal formation of specific T cells and IgGs. Notably, shedding of the H3N2 virus challenge and lung damage were reduced in both cases [ 68 ].…”

Section: Development Of Np-based Broadly Protective Vaccine Prototypesmentioning

confidence: 99%

Nucleoprotein as a Promising Antigen for Broadly Protective Influenza Vaccines

Rak,

Isakova-Sivak,

Rudenko

2023

Vaccines

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Annual vaccination is considered as the main preventive strategy against seasonal influenza. Due to the highly variable nature of major viral antigens, such as hemagglutinin (HA) and neuraminidase (NA), influenza vaccine strains should be regularly updated to antigenically match the circulating viruses. The influenza virus nucleoprotein (NP) is much more conserved than HA and NA, and thus seems to be a promising target for the design of improved influenza vaccines with broad cross-reactivity against antigenically diverse influenza viruses. Traditional subunit or recombinant protein influenza vaccines do not contain the NP antigen, whereas live-attenuated influenza vaccines (LAIVs) express the viral NP within infected cells, thus inducing strong NP-specific antibodies and T-cell responses. Many strategies have been explored to design broadly protective NP-based vaccines, mostly targeted at the T-cell mode of immunity. Although the NP is highly conserved, it still undergoes slow evolutionary changes due to selective immune pressure, meaning that the particular NP antigen selected for vaccine design may have a significant impact on the overall immunogenicity and efficacy of the vaccine candidate. In this review, we summarize existing data on the conservation of the influenza A viral nucleoprotein and review the results of preclinical and clinical trials of NP-targeting influenza vaccine prototypes, focusing on the ability of NP-specific immune responses to protect against diverse influenza viruses.

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Immunization with matrix-, nucleoprotein and neuraminidase protects against H3N2 influenza challenge in pH1N1 pre-exposed pigs

Cited by 13 publications

References 50 publications

Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunisation in the pig lung

Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunisation in the pig lung

Swine influenza A virus: challenges and novel vaccine strategies

Nucleoprotein as a Promising Antigen for Broadly Protective Influenza Vaccines

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