A “universal” human influenza A vaccine

Fiers, Walter; Filette, Marina De; Birkett, Ashley; Neirynck, Sabine; Jou, Willy Min

doi:10.1016/j.virusres.2004.02.030

Cited by 205 publications

(132 citation statements)

References 11 publications

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“…Every year, on average, influenza virus infects 5-15% of the world's population, resulting in approximately 500,000 deaths [1]. In addition, infection with IAV creates a window of susceptibility to secondary bacterial infections.…”

Section: Introductionmentioning

confidence: 99%

Bacterial Lipopolysaccharide Inhibits Influenza Virus Infection of Human Macrophages and the Consequent Induction of CD8+ T Cell Immunity

et al. 2013

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It is well established that infection with influenza A virus (IAV) facilitates secondary bacterial disease. However, there is a growing body of evidence that the microbial context in which IAV infection occurs can affect both innate and adaptive responses to the virus. To date, these studies have been restricted to murine models of disease and the relevance of these findings in primary human cells remains to be elucidated. Here, we show that pre-stimulation of primary human monocyte-derived macrophages (MDMs) with the bacterial ligand lipopolysaccharide (LPS) reduces the ability of IAV to infect these cells. The inhibition of IAV infection was associated with a reduced transcription of viral RNA and the ability of LPS to induce an anti-viral/type I interferon response in human MDMs. We demonstrated that this reduced rate of viral infection is associated with a reduced ability to present a model antigen to autologous CD8+ T cells. Taken together, these data provide the first evidence that exposure to bacterial ligands like LPS can play an important role in modulating the immune response of primary human immune cells towards IAV infection, which may then have important consequences for the development of the host's adaptive immune response.

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Section: Introductionmentioning

confidence: 99%

Bacterial Lipopolysaccharide Inhibits Influenza Virus Infection of Human Macrophages and the Consequent Induction of CD8+ T Cell Immunity

et al. 2013

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“…Its ectodomain, M2e, is a minor but evolutionary constant epitope, remarkably conserved between antigenically distant influenza A virus strains of either human or avian origin (15). Indeed, the ability of M2e-based vaccine to provide cross-protective immu-nity was first demonstrated by Neirynck et al (16).…”

mentioning

confidence: 99%

A Novel Subnucleocapsid Nanoplatform for Mucosal Vaccination against Influenza Virus That Targets the Ectodomain of Matrix Protein 2

Hervé

Raliou

Bourdieu

et al. 2014

J Virol

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In this study, subnucleocapsid nanorings formed by the recombinant nucleoprotein (N) of the respiratory syncytial virus were evaluated as a platform to anchor heterologous antigens. The ectodomain of the influenza virus A matrix protein 2 (M2e) is highly conserved and elicits protective antibodies when it is linked to an immunogenic carrier, making it a promising target to develop universal influenza vaccines. In this context, one or three M2e copies were genetically linked to the C terminus of N to produce N-M2e and N-3M2e chimeric recombinant nanorings. Mice were immunized intranasally with N-M2e or N-3M2e or with M2e or 3M2e control peptides. N-3M2e-vaccinated mice showed the strongest mucosal and systemic antibody responses. These mice presented a reduced viral load and minor weight loss, and all survived upon challenge with influenza virus A/PR8/34 (H1N1) (PR8). We compared the intranasal route to the subcutaneous route of N-3M2e immunization. Only the intranasal route induced a strong local IgA response and led to the protection of mice upon challenge. Finally, we demonstrated that the induction of anti-M2e antibodies by N-3M2e is not impaired by preexisting anti-N immunity. Overall, these results show that the N nanoring is a potent carrier for mucosal delivery of vaccinal antigens.

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“…Attention has been focused on the conserved antigens, mainly NP, M1 or M2, inducing protective immunity. To broaden the protection efficacy against IAV of various subtypes, novel approaches using adjuvants or vectors for antigen delivery such as recombinant viruses, or virus-like particles, bacterial expression systems, or plasmid DNA have been described (Fiers et al, 2004;Hillaire et al, 2011;Lillie et al, 2012). From many recent studies it can be concluded that HA2 gp, the conserved part of HA, can also be a good inductor of cross-protection.…”

Section: Resultsmentioning

confidence: 99%

“…However, due to the conservation of M2 among IAVs of various HA subtype, attention has been focused on this protein, especially on its ectodomain (eM2) (Mozdanowska et al, 1999;Neirynck et al, 1999;Frace et al, 1999). Enhanced levels of eM2-specific antibodies, produced following a targeted immunization with eM2, were shown to be protective (Mozdzanowska et al, 2003;Fiers et al, 2004;Mozdzanowska et al, 2007). Moreover, during IAV infection, antibodies against internal proteins NP, PB1, and PA have also been detected, but no unambiguous protective effect has been attributed to them.…”

Section: Cd4mentioning

confidence: 99%

HA2 glycopolypeptide of influenza A virus and antiviral immunity

Varečková¹,

Mucha²,

Kostolanský³

2013

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Summary. -Influenza A viruses (IAVs) cause acute respiratory infections in humans against which an effective prevention has not yet been developed due to their high variability and broad host specificity. The permanent threat of arising new influenza pandemic is represented by avian viruses which after their interspecies transmission can cause a disease with a devastating impact on humans lacking the specific immunity. Since the current vaccines inducing virus-neutralizing (VN) antibodies are targeted at a variable globular part of hemagglutinin (HA), their efficacy is limited and they need permanent updating. On the other hand, conserved IAV antigens such as proton channel M2, membrane protein M1 or nucleoprotein (NP) do not induce VN antibodies, but they do induce heterosubtypic protection resulting in the reduction of virus replication and an improved recovery from the disease. From this point of view recent attention has also been focused on the conserved part of HA, its HA2 glycoprotein (HA2). The main aspects revealing a contribution of HA2 gp to protective immunity are discussed in this review.

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A “universal” human influenza A vaccine

Cited by 205 publications

References 11 publications

Bacterial Lipopolysaccharide Inhibits Influenza Virus Infection of Human Macrophages and the Consequent Induction of CD8+ T Cell Immunity

Bacterial Lipopolysaccharide Inhibits Influenza Virus Infection of Human Macrophages and the Consequent Induction of CD8+ T Cell Immunity

A Novel Subnucleocapsid Nanoplatform for Mucosal Vaccination against Influenza Virus That Targets the Ectodomain of Matrix Protein 2

HA2 glycopolypeptide of influenza A virus and antiviral immunity

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