scholarly journals Recombinant Soluble, Multimeric HA and NA Exhibit Distinctive Types of Protection against Pandemic Swine-Origin 2009 A(H1N1) Influenza Virus Infection in Ferrets

2010 ◽  
Vol 84 (19) ◽  
pp. 10366-10374 ◽  
Author(s):  
Berend Jan Bosch ◽  
Rogier Bodewes ◽  
Robert P. de Vries ◽  
Joost H. C. M. Kreijtz ◽  
Willem Bartelink ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Expression System ◽  
Influenza Virus Infection ◽  
Body Weight Loss ◽  
H1n1 Influenza ◽  
Clinical Effects ◽  
Lung Pathology ◽  
Challenge Inoculation ◽  
Mammalian Expression ◽  
Vaccine Potential

ABSTRACT The emergence and subsequent swift and global spread of the swine-origin influenza virus A(H1N1) in 2009 once again emphasizes the strong need for effective vaccines that can be developed rapidly and applied safely. With this aim, we produced soluble, multimeric forms of the 2009 A(H1N1) HA (sHA3) and NA (sNA4) surface glycoproteins using a virus-free mammalian expression system and evaluated their efficacy as vaccines in ferrets. Immunization twice with 3.75-μg doses of these antigens elicited strong antibody responses, which were adjuvant dependent. Interestingly, coadministration of both antigens strongly enhanced the HA-specific but not the NA-specific responses. Distinct patterns of protection were observed upon challenge inoculation with the homologous H1N1 virus. Whereas vaccination with sHA3 dramatically reduced virus replication (e.g., by lowering pulmonary titers by about 5 log10 units), immunization with sNA4 markedly decreased the clinical effects of infection, such as body weight loss and lung pathology. Clearly, optimal protection was achieved by the combination of the two antigens. Our observations demonstrate the great vaccine potential of multimeric HA and NA ectodomains, as these can be easily, rapidly, flexibly, and safely produced in high quantities. In particular, our study underscores the underrated importance of NA in influenza vaccination, which we found to profoundly and specifically contribute to protection by HA. Its inclusion in a vaccine is likely to reduce the HA dose required and to broaden the protective immunity.

scholarly journals Next Generation of Computationally Optimized Broadly Reactive HA Vaccines Elicited Cross-Reactive Immune Responses and Provided Protection against H1N1 Virus Infection

Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 793
Author(s):  
Ying Huang ◽  
Monique S. França ◽  
James D. Allen ◽  
Hua Shi ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Immune Responses ◽  
H1n1 Virus ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Wild Type ◽  
Influenza A H1n1

Vaccination is the best way to prevent influenza virus infections, but the diversity of antigenically distinct isolates is a persistent challenge for vaccine development. In order to conquer the antigenic variability and improve influenza virus vaccine efficacy, our research group has developed computationally optimized broadly reactive antigens (COBRAs) in the form of recombinant hemagglutinins (rHAs) to elicit broader immune responses. However, previous COBRA H1N1 vaccines do not elicit immune responses that neutralize H1N1 virus strains in circulation during the recent years. In order to update our COBRA vaccine, two new candidate COBRA HA vaccines, Y2 and Y4, were generated using a new seasonal-based COBRA methodology derived from H1N1 isolates that circulated during 2013–2019. In this study, the effectiveness of COBRA Y2 and Y4 vaccines were evaluated in mice, and the elicited immune responses were compared to those generated by historical H1 COBRA HA and wild-type H1N1 HA vaccines. Mice vaccinated with the next generation COBRA HA vaccines effectively protected against morbidity and mortality after infection with H1N1 influenza viruses. The antibodies elicited by the COBRA HA vaccines were highly cross-reactive with influenza A (H1N1) pdm09-like viruses isolated from 2009 to 2021, especially with the most recent circulating viruses from 2019 to 2021. Furthermore, viral loads in lungs of mice vaccinated with Y2 and Y4 were dramatically reduced to low or undetectable levels, resulting in minimal lung injury compared to wild-type HA vaccines following H1N1 influenza virus infection.

scholarly journals Inhibition of H1N1 influenza virus by selenium nanoparticles loaded with zanamivir through p38 and JNK signaling pathways

RSC Advances ◽  
2017 ◽  
Vol 7 (56) ◽  
pp. 35290-35296 ◽  
Author(s):  
Zhengfang Lin ◽  
Yinghua Li ◽  
Min Guo ◽  
Misi Xiao ◽  
Changbing Wang ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Signaling Pathways ◽  
Clinical Application ◽  
Influenza Virus Infection ◽  
Aqueous Solubility ◽  
H1n1 Influenza ◽  
Solubility Limit ◽  
H1n1 Influenza Virus ◽  
Jnk Signaling

Zanamivir is an effective drug for influenza virus infection, but strong molecular polarity and aqueous solubility limit its clinical application.

Electrocardiographic Abnormalities in Patients With Novel H1N1 Influenza Virus Infection

2010 ◽  
Vol 106 (10) ◽  
pp. 1517-1519 ◽  
Author(s):  
Nikolaos Akritidis ◽  
Maria Mastora ◽  
Gerasimos Baxevanos ◽  
Georgios Dimos ◽  
Georgios Pappas
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
H1n1 Influenza Virus ◽  
Novel H1n1 Influenza ◽  
Electrocardiographic Abnormalities

scholarly journals Serum High-Mobility-Group Box 1 as a Biomarker and a Therapeutic Target during Respiratory Virus Infections

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Mira C. Patel ◽  
Kari Ann Shirey ◽  
Marina S. Boukhvalova ◽  
Stefanie N. Vogel ◽  
Jorge C. G. Blanco
Keyword(s):  
Influenza Virus ◽  
Virus Infection ◽  
Influenza A ◽  
Influenza Virus Infection ◽  
High Mobility ◽  
Influenza B Virus ◽  
Influenza B ◽  
Lung Pathology ◽  
B Virus ◽  
Cotton Rats

ABSTRACT Host-derived “danger-associated molecular patterns” (DAMPs) contribute to innate immune responses and serve as markers of disease progression and severity for inflammatory and infectious diseases. There is accumulating evidence that generation of DAMPs such as oxidized phospholipids and high-mobility-group box 1 (HMGB1) during influenza virus infection leads to acute lung injury (ALI). Treatment of influenza virus-infected mice and cotton rats with the Toll-like receptor 4 (TLR4) antagonist Eritoran blocked DAMP accumulation and ameliorated influenza virus-induced ALI. However, changes in systemic HMGB1 kinetics during the course of influenza virus infection in animal models and humans have yet to establish an association of HMGB1 release with influenza virus infection. To this end, we used the cotton rat model that is permissive to nonadapted strains of influenza A and B viruses, respiratory syncytial virus (RSV), and human rhinoviruses (HRVs). Serum HMGB1 levels were measured by an enzyme-linked immunosorbent assay (ELISA) prior to infection until day 14 or 18 post-infection. Infection with either influenza A or B virus resulted in a robust increase in serum HMGB1 levels that decreased by days 14 to 18. Inoculation with the live attenuated vaccine FluMist resulted in HMGB1 levels that were significantly lower than those with infection with live influenza viruses. RSV and HRVs showed profiles of serum HMGB1 induction that were consistent with their replication and degree of lung pathology in cotton rats. We further showed that therapeutic treatment with Eritoran of cotton rats infected with influenza B virus significantly blunted serum HMGB1 levels and improved lung pathology, without inhibiting virus replication. These findings support the use of drugs that block HMGB1 to combat influenza virus-induced ALI. IMPORTANCE Influenza virus is a common infectious agent causing serious seasonal epidemics, and there is urgent need to develop an alternative treatment modality for influenza virus infection. Recently, host-derived DAMPs, such as oxidized phospholipids and HMGB1, were shown to be generated during influenza virus infection and cause ALI. To establish a clear link between influenza virus infection and HMGB1 as a biomarker, we have systematically analyzed temporal patterns of serum HMGB1 release in cotton rats infected with nonadapted strains of influenza A and B viruses and compared these patterns with a live attenuated influenza vaccine and infection by other respiratory viruses. Towards development of a new therapeutic modality, we show herein that blocking serum HMGB1 levels by Eritoran improves lung pathology in influenza B virus-infected cotton rats. Our study is the first report of systemic HMGB1 as a potential biomarker of severity in respiratory virus infections and confirms that drugs that block virus-induced HMGB1 ameliorate ALI.

scholarly journals Caffeoylquinic Acids Are Major Constituents with Potent Anti-Influenza Effects in Brazilian Green Propolis Water Extract

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Tomohiko Urushisaki ◽  
Tomoaki Takemura ◽  
Shigemi Tazawa ◽  
Mayuko Fukuoka ◽  
Junji Hosokawa-Muto ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Influenza A ◽  
Viral Infections ◽  
Influenza Virus Infection ◽  
Water Extract ◽  
H1n1 Influenza ◽  
Caffeoylquinic Acids ◽  
Cytoprotective Activity ◽  
Infected Cells ◽  
Brazilian Green Propolis

Influenza A viral infections reached pandemic levels in 1918, 1957, 1968, and, most recently, in 2009 with the emergence of the swine-origin H1N1 influenza virus. The development of novel therapeutics or prophylactics for influenza virus infection is urgently needed. We examined the evaluation of the anti-influenza virus (A/WSN/33 (H1N1)) activity of Brazilian green propolis water extract (PWE) and its constituents by cell viability and real-time PCR assays. Our findings showed strong evidence that PWE has an anti-influenza effect and demonstrate that caffeoylquinic acids are the active anti-influenza components of PWE. Furthermore, we have found that the amount of viral RNA per cell remained unchanged even in the presence of PWE, suggesting that PWE has no direct impact on the influenza virus but may have a cytoprotective activity by affecting internal cellular process. These findings indicate that caffeoylquinic acids are the active anti-influenza components of PWE. Above findings might facilitate the prophylactic application of natural products and the realization of novel anti-influenza drugs based on caffeoylquinic acids, as well as further the understanding of cytoprotective intracellular mechanisms in influenza virus-infected cells.

scholarly journals Humans and Ferrets with Prior H1N1 Influenza Virus Infections Do Not Exhibit Evidence of Original Antigenic Sin after Infection or Vaccination with the 2009 Pandemic H1N1 Influenza Virus

2014 ◽  
Vol 21 (5) ◽  
pp. 737-746 ◽  
Author(s):  
Christopher D. O'Donnell ◽  
Amber Wright ◽  
Leatrice Vogel ◽  
Kobporn Boonnak ◽  
John J. Treanor ◽  
...  
Keyword(s):  
Immune Response ◽  
Influenza Virus ◽  
Virus Infection ◽  
Antibody Response ◽  
Influenza Virus Infection ◽  
H1n1 Influenza ◽  
T Cell Response ◽  
Pandemic H1n1 ◽  
H1n1 Influenza Virus ◽  
Original Antigenic Sin

ABSTRACTThe hypothesis of original antigenic sin (OAS) states that the imprint established by an individual's first influenza virus infection governs the antibody response thereafter. Subsequent influenza virus infection results in an antibody response against the original infecting virus and an impaired immune response against the newer influenza virus. The purpose of our study was to seek evidence of OAS after infection or vaccination with the 2009 pandemic H1N1 (2009 pH1N1) virus in ferrets and humans previously infected with H1N1 viruses with various antigenic distances from the 2009 pH1N1 virus, including viruses from 1935 through 1999. In ferrets, seasonal H1N1 priming did not diminish the antibody response to infection or vaccination with the 2009 pH1N1 virus, nor did it diminish the T-cell response, indicating the absence of OAS in seasonal H1N1 virus-primed ferrets. Analysis of paired samples of human serum taken before and after vaccination with a monovalent inactivated 2009 pH1N1 vaccine showed a significantly greater-fold rise in the titer of antibody against the 2009 pH1N1 virus than against H1N1 viruses that circulated during the childhood of each subject. Thus, prior experience with H1N1 viruses did not result in an impairment of the antibody response against the 2009 pH1N1 vaccine. Our data from ferrets and humans suggest that prior exposure to H1N1 viruses did not impair the immune response against the 2009 pH1N1 virus.

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