scholarly journals DNA-Epitope Vaccine Provided Efficient Protection to Mice Against Lethal Dose of Influenza A Virus H1N1

2014 ◽  
Vol 27 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Huiling Wei ◽  
Stephen D. Lenz ◽  
David H. Thompson ◽  
Roman M. Pogranichniy
2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S410-S411
Author(s):  
Shinya Shano ◽  
Keita Fukao ◽  
Takeshi Noshi ◽  
Kenji Sato ◽  
Masashi Sakuramoto ◽  
...  

Abstract Background Baloxavir acid (BXA), an active form of orally available prodrug baloxavir marboxil (BXM, formerly S-033188), is a novel small molecule inhibitor of cap-dependent endonuclease (CEN) of influenza A and B virus, and was recently launched for the treatment of acute and uncomplicated influenza with single dosing of BXM (the trade name XOFLUZA™) in Japan in March 2018. Here, we evaluated the prophylactic efficacy of BXA in mice lethally infected with influenza A virus. Methods T1/2 of BXA in human is more than 10 times longer than that in mice. Therefore, suspension of BXA was subcutaneously administered at 0.8 or 1.6 mg/kg in mice to maintain the plasma concentration of BXA as seen in humans, and then mice were intranasally inoculated with a lethal dose of A/PR/8/34 strain at 48, 72, or 96 hours after the administration of BXA. Survival time and body weight change were then monitored through a 28-day period after virus infection. Mice were euthanized and regarded as dead if their body weights were lower than 70% of the initial body weights according to humane endpoints. Results Single dosing of BXA (1.6 mg/kg) completely eliminated mortality in mice, when the mice were administrated the drug at 48, 72, or 96 hours before virus infection (Figure 1). BXA treatment also significantly prevented body weight loss, consistent with the prolonged survival. Conclusion Prophylactic dosing of BXA exhibited significant protective efficacy against mortality and body weight loss in mice following a lethal infection with influenza A virus. The significant prophylactic efficacy observed in our mouse model suggests the potential utility of BXM for the prophylaxis of influenza in human. Disclosures S. Shano, Shionogi & Co., Ltd.: Employee, Salary. K. Fukao, Shionogi & Co., Ltd.: Employee, Salary. T. Noshi, Shionogi & Co., Ltd.: Employee, Salary. K. Sato, Shionogi & Co., Ltd.: Employee, Salary. M. Sakuramoto, Shionogi & Co., Ltd.: Employee, Salary. K. Baba, Shionogi TechnoAdvance Research & Co., Ltd.: Employee, Salary. T. Shishido, Shionogi & Co., Ltd.: Employee, Salary. A. Naito, Shionogi & Co., Ltd.: Employee, Salary.


ChemMedChem ◽  
2013 ◽  
Vol 9 (1) ◽  
pp. 129-150 ◽  
Author(s):  
Mafalda Pagano ◽  
Daniele Castagnolo ◽  
Martina Bernardini ◽  
Anna Lucia Fallacara ◽  
Ilaria Laurenzana ◽  
...  

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Seung-Taek Yu ◽  
Cuc Thi Bui ◽  
Do Thi Hoang Kim ◽  
Anh V. T. Nguyen ◽  
Thuy Tien Thi Trinh ◽  
...  

1941 ◽  
Vol 73 (1) ◽  
pp. 43-55 ◽  
Author(s):  
R. M. Taylor

Following intranasal inoculation of influenza A virus (strain PR8) there is a rapid increase of the virus in the lungs which with large doses reaches a maximum within 24 hours. With smaller doses, although the proportional increase is greater, the maximum concentration is not reached until 48 hours following inoculation. If a lethal dose is administered, the ultimate concentration of the virus in the lungs is the same, irrespective of the size of the dose. If a sublethal dose is given, the titer of the virus in the lungs does not achieve the titer reached in mice receiving a lethal dose. Within 48 hours following inoculation of a sublethal dose the lungs of a mouse may contain at least 76,000 M.L.D., yet the mouse survives. The intranasal instillation of sterile fluid (distilled water, varying concentrations of NaCl, broth, or 10 per cent normal serum) into a mouse sublethally infected produces a sharp rise in the virus content of the lung usually followed by death within 3 to 8 days. If, however, the instillate consists of 10 per cent immune serum, there is no rise in the virus titer, and no apparent harm results from the instillation. The implications of these phenomena are discussed and an hypothesis presented to explain their occurrence.


2011 ◽  
Vol 18 (9) ◽  
pp. 1401-1405 ◽  
Author(s):  
Elisabeth Huijskens ◽  
John Rossen ◽  
Paul Mulder ◽  
Ruud van Beek ◽  
Hennie van Vugt ◽  
...  

ABSTRACTThe emergence of a new influenza A virus (H1N1) variant in 2009 led to a worldwide vaccination program, which was prepared in a relatively short period of time. This study investigated the humoral immunity against this virus before and after vaccination with a 2009 influenza A virus (H1N1) monovalent MF59-adjuvanted vaccine, as well as the persistence of vaccine-induced antibodies. Our prospective longitudinal study included 498 health care workers (mean age, 43 years; median age, 44 years). Most (89%) had never or only occasionally received a seasonal influenza virus vaccine, and 11% were vaccinated annually (on average, for >10 years). Antibody titers were determined by a hemagglutination inhibition (HI) assay at baseline, 3 weeks after the first vaccination, and 5 weeks and 7 months after the second vaccination. Four hundred thirty-five persons received two doses of the 2009 vaccine. After the first dose, 79.5% developed a HI titer of ≥40. This percentage increased to 83.3% after the second dose. Persistent antibodies were found in 71.9% of the group that had not received annual vaccinations and in 43.8% of the group that had received annual vaccinations. The latter group tended to have lower HI titers (P=0.09). With increasing age, HI titers decreased significantly, by 2.4% per year. A single dose of the 2009 vaccine was immunogenic in almost 80% of the study population, whereas an additional dose resulted in significantly increased titers only in persons over 50. Finally, a reduced HI antibody response against the 2009 vaccine was found in adults who had previously received seasonal influenza virus vaccination. More studies on the effect of yearly seasonal influenza virus vaccination on the immune response are warranted.


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