scholarly journals Long-Lasting Mucosal and Systemic Immunity against Influenza A Virus Is Significantly Prolonged and Protective by Nasal Whole Influenza Immunization with Mucosal Adjuvant N3 and DNA-Plasmid Expressing Flagellin in Aging In- and Outbred Mice

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 64 ◽  
Author(s):  
Jorma Hinkula ◽  
Sanna Nyström ◽  
Claudia Devito ◽  
Andreas Bråve ◽  
Steven E. Applequist
Keyword(s):  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Inbred Mouse ◽  
Herd Immunity ◽  
Serum Antibody ◽  
Mouse Strains ◽  
Virus Challenge ◽  
Influenza A H1n1

Background: Vaccination is commonly used to prevent and control influenza infection in humans. However, improvements in the ease of delivery and strength of immunogenicity could markedly improve herd immunity. The aim of this pre-clinical study is to test the potential improvements to existing intranasal delivery of formalin-inactivated whole Influenza A vaccines (WIV) by formulation with a cationic lipid-based adjuvant (N3). Additionally, we combined WIV and N3 with a DNA-encoded TLR5 agonist secreted flagellin (pFliC(-gly)) as an adjuvant, as this adjuvant has previously been shown to improve the effectiveness of plasmid-encoded DNA antigens. Methods: Outbred and inbred mouse strains were intranasally immunized with unadjuvanted WIV A/H1N1/SI 2006 or WIV that was formulated with N3 alone. Additional groups were immunized with WIV and N3 adjuvant combined with pFliC(-gly). Homo and heterotypic humoral anti-WIV immune responses were assayed from serum and lung by ELISA and hemagglutination inhibition assay. Homo and heterotypic cellular immune responses to WIV and Influenza A NP were also determined. Results: WIV combined with N3 lipid adjuvant the pFliC(-gly) significantly increased homotypic influenza specific serum antibody responses (>200-fold), increased the IgG2 responses, indicating a mixed Th1/Th2-type immunity, and increased the HAI-titer (>100-fold). Enhanced cell-mediated IFNγ secreting influenza directed CD4+ and CD8+ T cell responses (>40-fold) to homotypic and heterosubtypic influenza A virus and peptides. Long-term and protective immunity was obtained. Conclusions: These results indicate that inactivated influenza virus that was formulated with N3 cationic adjuvant significantly enhanced broad systemic and mucosal influenza specific immune responses. These responses were broadened and further increased by incorporating DNA plasmids encoding FliC from S. typhimurum as an adjuvant providing long lasting protection against heterologous Influenza A/H1N1/CA09pdm virus challenge.

scholarly journals Evaluation of Live Attenuated Influenza A Virus H6 Vaccines in Mice and Ferrets

2008 ◽  
Vol 83 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Zhongying Chen ◽  
Celia Santos ◽  
Amy Aspelund ◽  
Laura Gillim-Ross ◽  
Hong Jin ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Serum Antibody ◽  
Cross Reactivity ◽  
Phenotypic Properties ◽  
Vaccine Candidates ◽  
Virus Challenge ◽  
Avian Influenza A Virus ◽  
Internal Gene

ABSTRACT Avian influenza A virus A/teal/HK/W312/97 (H6N1) possesses seven gene segments that are highly homologous to those of highly pathogenic human influenza H5N1 viruses, suggesting that a W312-like H6N1 virus might have been involved in the generation of the A/HK/97 H5N1 viruses. The continuous circulation and reassortment of influenza H6 subtype viruses in birds highlight the need to develop an H6 vaccine to prevent potential influenza pandemics caused by the H6 viruses. Based on the serum antibody cross-reactivity data obtained from 14 different H6 viruses from Eurasian and North American lineages, A/duck/HK/182/77, A/teal/HK/W312/97, and A/mallard/Alberta/89/85 were selected to produce live attenuated H6 candidate vaccines. Each of the H6 vaccine strains is a 6:2 reassortant ca virus containing HA and NA gene segments from an H6 virus and the six internal gene segments from cold-adapted A/Ann Arbor/6/60 (AA ca), the master donor virus that is used to make live attenuated influenza virus FluMist (intranasal) vaccine. All three H6 vaccine candidates exhibited phenotypic properties of temperature sensitivity (ts), ca, and attenuation (att) conferred by the internal gene segments from AA ca. Intranasal administration of a single dose of the three H6 ca vaccine viruses induced neutralizing antibodies in mice and ferrets and fully protected mice and ferrets from homologous wild-type (wt) virus challenge. Among the three H6 vaccine candidates, the A/teal/HK/W312/97 ca virus provided the broadest cross-protection against challenge with three antigenically distinct H6 wt viruses. These data support the rationale for further evaluating the A/teal/HK/W312/97 ca vaccine in humans.

scholarly journals Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

2017 ◽  
Vol 199 (4) ◽  
pp. 1333-1341 ◽  
Author(s):  
Claire M. Tully ◽  
Senthil Chinnakannan ◽  
Caitlin E. Mullarkey ◽  
Marta Ulaszewska ◽  
Francesca Ferrara ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Virus Challenge ◽  
Cellular Immune Responses ◽  
Cellular Immune

cGAMP loading enhances the immunogenicity of VLP vaccines

2020 ◽  
Author(s):  
Lise Chauveau ◽  
Anne Bridgeman ◽  
Tiong Kit Tan ◽  
Ryan Beveridge ◽  
Joe Frost ◽  
...  
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Viral Vectors ◽  
Serum Antibody ◽  
Gag Protein ◽  
Virus Like Particles ◽  
Virus Challenge ◽  
Enveloped Virus ◽  
Viral Vaccine

AbstractCyclic GMP-AMP (cGAMP) is an immunostimulatory second messenger produced by cGAS that activates STING. Soluble cGAMP acts as an adjuvant when administered with antigens. cGAMP is also incorporated into enveloped virus particles during budding. We hypothesised that inclusion of the adjuvant cGAMP within viral vaccine vectors would promote adaptive immunity against vector antigens. We immunised mice with virus-like particles (VLPs) containing the HIV-1 Gag protein and VSV-G. Inclusion of cGAMP within these VLPs augmented splenic VLP-specific CD4 and CD8 T cell responses. It also increased VLP- and VSV-G-specific serum antibody titres and enhanced in vitro virus neutralisation. The superior antibody response was accompanied by increased numbers of T follicular helper cells in draining lymph nodes. Vaccination with cGAMP-loaded VLPs containing haemagglutinin induced high titres of influenza A virus neutralising antibodies and conferred protection following subsequent influenza A virus challenge. Together, these results show that incorporating cGAMP into VLPs enhances their immunogenicity, making cGAMP-VLPs an attractive platform for novel vaccination strategies.Short summarycGAMP is an innate immune signalling molecule that can be transmitted between cells by inclusion in enveloped virions. This study demonstrates enhanced immunogenicity of HIV-derived virus-like particles containing cGAMP. Viral vectors loaded with cGAMP may thus be potent vaccines.

scholarly journals Regulation of Host Immune Responses against Influenza A Virus Infection by Mitogen-Activated Protein Kinases (MAPKs)

2020 ◽  
Vol 8 (7) ◽  
pp. 1067
Author(s):  
Jiabo Yu ◽  
Xiang Sun ◽  
Jian Yi Gerald Goie ◽  
Yongliang Zhang
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Influenza Infection ◽  
Influenza Viruses ◽  
Mitogen Activated Protein Kinase ◽  
Viral Diseases ◽  
Cytokine Storm ◽  
Mitogen Activated Protein

Influenza is a major respiratory viral disease caused by infections from the influenza A virus (IAV) that persists across various seasonal outbreaks globally each year. Host immune response is a key factor determining disease severity of influenza infection, presenting an attractive target for the development of novel therapies for treatments. Among the multiple signal transduction pathways regulating the host immune activation and function in response to IAV infections, the mitogen-activated protein kinase (MAPK) pathways are important signalling axes, downstream of various pattern recognition receptors (PRRs), activated by IAVs that regulate various cellular processes in immune cells of both innate and adaptive immunity. Moreover, aberrant MAPK activation underpins overexuberant production of inflammatory mediators, promoting the development of the “cytokine storm”, a characteristic of severe respiratory viral diseases. Therefore, elucidation of the regulatory roles of MAPK in immune responses against IAVs is not only essential for understanding the pathogenesis of severe influenza, but also critical for developing MAPK-dependent therapies for treatment of respiratory viral diseases. In this review, we will summarise the current understanding of MAPK functions in both innate and adaptive immune response against IAVs and discuss their contributions towards the cytokine storm caused by highly pathogenic influenza viruses.

scholarly journals Offspring born to influenza A virus infected pregnant mice have increased susceptibility to viral and bacterial infections in early life

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Henning Jacobsen ◽  
Kerstin Walendy-Gnirß ◽  
Nilgün Tekin-Bubenheim ◽  
Nancy Mounogou Kouassi ◽  
Isabel Ben-Batalla ◽  
...  
Keyword(s):  
Immune Responses ◽  
Influenza A Virus ◽  
Alveolar Macrophages ◽  
Early Life ◽  
Influenza A ◽  
Influenza Infection ◽  
Later Life ◽  
Influenza B ◽  
Second Hit ◽  
Maternal Influenza

AbstractInfluenza during pregnancy can affect the health of offspring in later life, among which neurocognitive disorders are among the best described. Here, we investigate whether maternal influenza infection has adverse effects on immune responses in offspring. We establish a two-hit mouse model to study the effect of maternal influenza A virus infection (first hit) on vulnerability of offspring to heterologous infections (second hit) in later life. Offspring born to influenza A virus infected mothers are stunted in growth and more vulnerable to heterologous infections (influenza B virus and MRSA) than those born to PBS- or poly(I:C)-treated mothers. Enhanced vulnerability to infection in neonates is associated with reduced haematopoetic development and immune responses. In particular, alveolar macrophages of offspring exposed to maternal influenza have reduced capacity to clear second hit pathogens. This impaired pathogen clearance is partially reversed by adoptive transfer of alveolar macrophages from healthy offspring born to uninfected dams. These findings suggest that maternal influenza infection may impair immune ontogeny and increase susceptibility to early life infections of offspring.

scholarly journals Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus, Respiratory Syncytial Virus and Influenza A Virus

Viruses ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 234
Author(s):  
Sarah Al-Beltagi ◽  
Cristian Alexandru Preda ◽  
Leah V. Goulding ◽  
Joe James ◽  
Juan Pu ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Respiratory Syncytial Virus ◽  
Influenza A Virus ◽  
Broad Spectrum ◽  
Influenza A ◽  
Respiratory Viruses ◽  
Influenza Viruses ◽  
Virus Challenge ◽  
2009 H1n1 ◽  
Syncytial Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca2+ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.

scholarly journals Impact of Influenza A Virus Shutoff Proteins on Host Immune Responses

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 629
Author(s):  
Megan M. Dunagan ◽  
Kala Hardy ◽  
Toru Takimoto
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Influenza A Virus ◽  
Influenza A ◽  
Human Populations ◽  
Lymphocyte Migration ◽  
Host Immune Responses ◽  
Mhc Molecules ◽  
The Impact

Influenza A virus (IAV) is a significant human pathogen that causes seasonal epidemics. Although various types of vaccines are available, IAVs still circulate among human populations, possibly due to their ability to circumvent host immune responses. IAV expresses two host shutoff proteins, PA-X and NS1, which antagonize the host innate immune response. By transcriptomic analysis, we previously showed that PA-X is a major contributor for general shutoff, while shutoff active NS1 specifically inhibits the expression of host cytokines, MHC molecules, and genes involved in innate immunity in cultured human cells. So far, the impact of these shutoff proteins in the acquired immune response in vivo has not been determined in detail. In this study, we analyzed the effects of PA-X and NS1 shutoff activities on immune response using recombinant influenza A/California/04/2009 viruses containing mutations affecting the expression of shutoff active PA-X and NS1 in a mouse model. Our data indicate that the virus without shutoff activities induced the strongest T and B cell responses. Both PA-X and NS1 reduced host immune responses, but shutoff active NS1 most effectively suppressed lymphocyte migration to the lungs, antibody production, and the generation of IAV specific CD4+ and CD8+ T cells. NS1 also prevented the generation of protective immunity against a heterologous virus challenge. These data indicate that shutoff active NS1 plays a major role in suppressing host immune responses against IAV infection.

scholarly journals QUALITATIVE DIFFERENCES IN THE ANTIGENIC COMPOSITION OF INFLUENZA A VIRUS STRAINS

1944 ◽  
Vol 79 (6) ◽  
pp. 633-647 ◽  
Author(s):  
William F. Friedewald
Keyword(s):  
Influenza A Virus ◽  
Influenza A ◽  
Serum Antibody ◽  
Allantoic Fluid ◽  
Influenza B Virus ◽  
Influenza B ◽  
Red Cell ◽  
Homologous Virus ◽  
Cell Adsorption ◽  
Virus Strains

A study of the PR8, Christie, Talmey, W.S., and swine strains of influenza A virus by means of antibody absorption tests revealed the following findings: 1. Serum antibody could be specifically absorbed with allantoic fluid containing influenza virus or, more effectively, with concentrated suspensions of virus obtained from allantoic fluid by high-speed centrifugation or by the red cell adsorption and elution technique. Normal allantoic fluid, or the centrifugalized sediment therefrom, failed to absorb antibodies. Influenza B virus (Lee) caused no detectable absorption of antibody from antisera directed against influenza A virus strains, but it specifically absorbed antibody from Lee antisera. 2. The neutralizing, agglutination-inhibiting, and complement-fixing anti-bodies in ferret antisera were completely absorbed only by the homologous virus strain, even though 2 absorptions were carried out with large amounts of heterologous virus strains. 3. PR8 virus appeared to have the broadest range of specific antigenic components for it completely absorbed the heterologous antibodies in Christie and W.S. antisera and left only those antibodies which reacted with the respective homologous strains. The other virus strains (Christie, Talmey, W.S., swine) were more specific in the absorption of heterologous antibodies and completely removed only those antibodies which reacted with the absorbing virus. 4. The absorption tests revealed a higher degree of specificity and individuality of the virus strains than the various cross reactions previously reported. The strain specificity of PR8 virus was equally manifest in absorption tests with ferret sera and with human sera following vaccination. 5. The amount of homologous antibody remaining in a PR8 ferret serum after absorption with PR8 virus, obtained by the red cell adsorption and elution method, varied inversely as the concentration of virus used for absorption. A given concentration of virus, however, absorbed a greater percentage of neutralizing antibodies than either agglutination-inhibiting or complement-fixing antibodies.

Mixed polysaccharides derived from shiitake mushroom, Poriacocos, Ginger and Tangerine peel prevent the H1N1 virus infections in mice

2021 ◽  
Author(s):  
Diqi Yang ◽  
Minghua Hu ◽  
Hongmei Zhu ◽  
Jianguo Chen ◽  
Dehai Wang ◽  
...  
Keyword(s):  
Influenza A ◽  
Clinical Symptoms ◽  
H1n1 Virus ◽  
Global Public Health ◽  
Virus Infections ◽  
Shiitake Mushroom ◽  
Virus Challenge ◽  
Influenza A H1n1 ◽  
Public Health Challenges ◽  
Cellular Immune

Abstract The pandemic influenza A (H1N1) virus spread globally and posed one of the most serious global public health challenges. The traditional Chinese medicine is served as a complementary treatment strategy with vaccine immunization. Here, we demonstrated the mixed polysaccharides (MPs) derived from shiitake mushroom, poriacocos, ginger and tyangerine peel prevent the H1N1 virus infections in mice. MPs pretreatment attenuated H1N1 virus-induced weight loss, clinical symptoms and death. The lymphocytes detection results showed the CD3+, CD19+ and CD25+ cell proportions were up-regulated in thymus under MPs pretreatment. Besides, MPs pretreatment reduced the inflammatory cell infiltration and increased the cell proportions of CD19+, CD25+ and CD278+ in lung. However, MPs treatment have no effective therapeutic effect after H1N1 virus challenge. The current study suggested that pretreatment with MPs could attenuate H1N1 virus-induced lung injury and up-regulate humoral and cellular immune responses in non- immunized mice.

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