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human influenza challenge

Raffael Nachbagauer, David Shore, Hua Yang, Scott K Johnson, Jon D Gabbard, S Mark Tompkins, Jens Wrammert, Patrick C Wilson, James Stevens, Rafi Ahmed, Florian Krammer, Ali H Ellebedy
Broadly cross-reactive antibodies that recognize conserved epitopes within the influenza virus hemagglutinin (HA) stalk domain are of particular interest for their potential use as therapeutic and prophylactic agents against multiple influenza virus subtypes including zoonotic virus strains. Here, we characterized four human HA stalk-reactive monoclonal antibodies (mAbs) for their binding breadth and affinity, in vitro neutralization capacity, and in vivo protective potential against an highly pathogenic avian influenza virus...
June 13, 2018: Journal of Virology
Erika Bongen, Francesco Vallania, Paul J Utz, Purvesh Khatri
BACKGROUND: Influenza infects tens of millions of people every year in the USA. Other than notable risk groups, such as children and the elderly, it is difficult to predict what subpopulations are at higher risk of infection. Viral challenge studies, where healthy human volunteers are inoculated with live influenza virus, provide a unique opportunity to study infection susceptibility. Biomarkers predicting influenza susceptibility would be useful for identifying risk groups and designing vaccines...
June 14, 2018: Genome Medicine
Meta Roestenberg, Marie-Astrid Hoogerwerf, Daniela M Ferreira, Benjamin Mordmüller, Maria Yazdanbakhsh
Controlled human infection (CHI) trials, in which healthy volunteers are experimentally infected, can accelerate the development of novel drugs and vaccines for infectious diseases of global importance. The use of CHI models is expanding from around 60 studies in the 1970s to more than 120 publications in this decade, primarily for influenza, rhinovirus, and malaria. CHI trials have provided landmark data for several registered drugs and vaccines, and have generated unprecedented scientific insights. Because of their invasive nature, CHI studies demand critical ethical review according to established frameworks...
June 8, 2018: Lancet Infectious Diseases
Kateri Bertran, Andrew Clark, David E Swayne
Airborne transmission of H5N1 highly pathogenic avian influenza (HPAI) viruses has occurred among poultry and from poultry to humans during home or live-poultry market slaughter of infected poultry, and such transmission has been experimentally reproduced. In this study, we investigated simple, practical changes in the processing of H5N1 virus-infected chickens to reduce infectious airborne particles and their transmission. Our findings suggest that containing the birds during the killing and bleeding first step by using a disposable plastic bag, a commonly available cooking pot widely used in Egypt (halla), or a bucket significantly reduces generation of infectious airborne particles and transmission to ferrets...
June 8, 2018: International Journal of Hygiene and Environmental Health
Sarah L Krein, Jeanmarie Mayer, Molly Harrod, Lauren E Weston, Lynn Gregory, Laura Petersen, Matthew H Samore, Frank A Drews
Importance: Using personal protective equipment (PPE) and transmission-based precautions are primary strategies for reducing the transmission of infectious agents. Objective: To identify and characterize failures in transmission-based precautions, including PPE use, by health care personnel that could result in self-contamination or transmission during routine, everyday hospital care. Design, Setting, and Participants: This qualitative study involved direct observation inside and outside patient rooms on clinical units from March 1, 2016, to November 30, 2016...
June 11, 2018: JAMA Internal Medicine
Sophie A Valkenburg, Olive T W Li, Athena Li, Maireid Bull, Thomas A Waldmann, Liyanage P Perera, Malik Peiris, Leo L M Poon
There is a diverse array of influenza viruses which circulate between different species, reassort and drift over time. Current seasonal influenza vaccines are ineffective in controlling these viruses. We have developed a novel universal vaccine which elicits robust T cell responses and protection against diverse influenza viruses in mouse and human models. Vaccine mediated protection was dependent on influenza-specific CD4+ T cells, whereby depletion of CD4+ T cells at either vaccination or challenge time points significantly reduced survival in mice...
June 7, 2018: Vaccine
Khrisdiana Putri, Nadeeka Wawegama, Jagoda Ignjatovic, Amir H Noormohammadi
Monitoring avian influenza (AI) infection and detecting silent infection in vaccinated chickens has been challenging due to the lack of effective serological diagnostic assays to differentiate between vaccinated and infected animals. Very few studies have identified suitable proteins in AI virus that can be used in successfully differentiating infected from vaccinated animals (DIVA). An HA2 peptide: HA2 position 197-201 (HA position 488-516) described by Khurana et al. (J Virol 85(23):12455-12463, 2011), was shown to have DIVA ability by differentiating H5N1-infected human sera in ELISA...
June 4, 2018: Archives of Virology
Xu Yang, Yijie Wang, Shengtao Zhao, Ran Wang, Changzheng Wang
Growing evidences indicate that bacteria are associated with pathogenesis of neutrophilic asthma. However, the long-term effect of airway bacterial colonization remains unclear. We sought to establish a murine model to simulate the airway inflammation of long-term bacterial colonization, and to assess the effects of bacteria on allergic airway disease (AAD). BALB/c mice were sensitized twice and subsequently challenged with ovalbumin (OVA) and exposed to low-dose Haemophilus influenzae for approximately 2 months...
May 18, 2018: Oncotarget
Jie Luo, Gang Lu, Shaotang Ye, Jiajun Ou, Cheng Fu, Xin Zhang, Xiangbin Wang, Ji Huang, Peixin Wu, Haibin Xu, Liyan Wu, Shoujun Li
As important companion animals, dogs may serve as intermediate hosts for transmitting influenza virus to humans. However, knowledge regarding H3N2 canine influenza virus (CIV) pathogenicity is not comprehensive, which directly affects the animal models of pathogenicity in H3N2 CIV vaccine research. Here, to assess H3N2 CIV pathogenicity, we utilized 30 ten-week-old purpose-bred beagles intratracheally or intranasally inoculated with 106 50 % egg-infectious dose. Intratracheal inoculation was more virulent to dogs than intranasal inoculation as shown by lung pathology score, histopathological changes, clinical symptoms, and body temperature...
May 31, 2018: Virus Research
Fengwei Zhang, Shanshan Wang, Yanan Wang, Xuechai Shang, Hongjuan Zhou, Long Cai
The reassortment of two highly pathogenic avian influenza (HPAI) H5N1 and H7N9 viruses presents a potential challenge to human health. The hemagglutinins (HAs) and neuraminidases (NAs) of these simultaneously circulating avian influenza viruses were evaluated using the pseudoparticle (pp) system. Native and mismatched virus pps were generated to investigate their biological characteristics. The HAs and NAs of the two viruses reassorted successfully to generate infectious viral particles. H7 was demonstrated to have the ability to reassort with NA from the H5N1 viruses, resulting in the generation of virions that were highly infectious to bronchial epithelial cells...
May 30, 2018: Virus Research
Joon-Yong Bae, Jin Il Kim, Sehee Park, Kirim Yoo, In-Ho Kim, Wooha Joo, Byng Hee Ryu, Mee Sook Park, Ilseob Lee, Man-Seong Park
Influenza virus that causes recurrent seasonal epidemics to humans can be controlled with vaccine and antiviral therapy. However, the medical treatments often exhibit limited efficacy in the elderly or immunosuppressed individuals. In these cases, daily uptake of probiotic microbes may be an option to bring in health benefits against influenza. Here we demonstrate the effects of probiotic Lactobacilli plantarum (Lp) and Leuconostoc mesenteroides (Lm) against seasonal and avian influenza viruses. As assessed by the plaque size reduction of human H1N1 and avian influenza H7N9 viruses including green fluorescent protein-tagged H1N1 strain in cells, the selected Lp and Lm strains restrained viral replication in mouse lungs with statistical significance...
April 23, 2018: Journal of Microbiology and Biotechnology
Abenaya Muralidharan, Caroline Gravel, Amparo Duran, Louise Larocque, Changgui Li, Adrian Zetner, Gary Van Domselaar, Lisheng Wang, Xuguang Li
Human infections by type B influenza virus constitute about 25% of all influenza cases. The viral hemagglutinin is comprised of two subunits, HA1 and HA2. While HA1 is constantly evolving in an unpredictable fashion, the HA2 subunit is highly conserved, making it a potential candidate for a universal vaccine. However, immunodominant epitopes in the HA2 subunit remain largely unknown. To delineate MHC Class I epitopes, we first identified 9-mer H-2Kd -restricted CD8 T cell epitopes in the HA2 domain by in silico analyses, followed by evaluating the immunodominance of these peptides in mice challenged with the virus...
May 21, 2018: Biochemical and Biophysical Research Communications
Santosh Dhakal, Sankar Renu, Shristi Ghimire, Yashavanth Shaan Lakshmanappa, Bradley T Hogshead, Ninoshkaly Feliciano-Ruiz, Fangjia Lu, Harm HogenEsch, Steven Krakowka, Chang Won Lee, Gourapura J Renukaradhya
Annually, swine influenza A virus (SwIAV) causes severe economic loss to swine industry. Currently used inactivated SwIAV vaccines administered by intramuscular injection provide homologous protection, but limited heterologous protection against constantly evolving field viruses, attributable to the induction of inadequate levels of mucosal IgA and cellular immune responses in the respiratory tract. A novel vaccine delivery platform using mucoadhesive chitosan nanoparticles (CNPs) administered through intranasal (IN) route has the potential to elicit strong mucosal and systemic immune responses in pigs...
2018: Frontiers in Immunology
Brian E Dawes, Birte Kalveram, Tetsuro Ikegami, Terry Juelich, Jennifer K Smith, Lihong Zhang, Arnold Park, Benhur Lee, Takashi Komeno, Yousuke Furuta, Alexander N Freiberg
Nipah and Hendra viruses are recently emerged bat-borne paramyxoviruses (genus Henipavirus) causing severe encephalitis and respiratory disease in humans with fatality rates ranging from 40-75%. Despite the severe pathogenicity of these viruses and their pandemic potential, no therapeutics or vaccines are currently approved for use in humans. Favipiravir (T-705) is a purine analogue antiviral approved for use in Japan against emerging influenza strains; and several phase 2 and 3 clinical trials are ongoing in the United States and Europe...
May 15, 2018: Scientific Reports
Nisha Singh, Zeeshan Ahmad, Navin Baid, Ashwani Kumar
Infectious diseases are a major challenge in management of human health worldwide. Recent literature suggests that host immune system could be modulated to ameliorate the pathogenesis of infectious disease. Heme oxygenase (HMOX1) is a key regulator of cellular signaling and it could be modulated using pharmacological reagents. HMOX1 is a cytoprotective enzyme that degrades heme to generate carbon monoxide (CO), biliverdin, and molecular iron. CO and biliverdin (or bilirubin derived from it) can restrict the growth of a few pathogens...
May 14, 2018: IUBMB Life
Charlotte L C J de Bree, Renoud J Marijnissen, Junda M Kel, Sietske K Rosendahl Huber, Peter Aaby, Christine Stabell Benn, Marcel V W Wijnands, Dimitri A Diavatopoulos, Reinout van Crevel, Leo A B Joosten, Mihai G Netea, John Dulos
Avian influenza A of the subtype H7N9 has been responsible for almost 1,600 confirmed human infections and more than 600 deaths since its first outbreak in 2013. Although sustained human-to-human transmission has not been reported yet, further adaptations to humans in the viral genome could potentially lead to an influenza pandemic, which may have severe consequences due to the absence of pre-existent immunity to this strain at population level. Currently there is no influenza A (H7N9) vaccine available. Therefore, in case of a pandemic outbreak, alternative preventive approaches are needed, ideally even independent of the type of influenza virus outbreak...
2018: Frontiers in Immunology
Louise C Rowntree, Thi H O Nguyen, Hanim Halim, Anthony W Purcell, Jamie Rossjohn, Stephanie Gras, Tom C Kotsimbos, Nicole A Mifsud
Human memory T cells that cross-react with epitopes from unrelated viruses can potentially modulate immune responses to subsequent infections by a phenomenon termed heterologous immunity. However, it is unclear whether similarities in structure rather than sequence underpin heterologous T cell cross-reactivity. In this study, we aimed to explore the mechanism of heterologous immunity involving immunodominant epitopes derived from common viruses restricted to high-frequency HLA allotypes (HLA-A*02:01, -B*07:02, and -B*08:01)...
May 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Byoung-Shik Shim, In Su Cheon, Eugene Lee, Sung-Moo Park, Youngjoo Choi, Dae-Im Jung, Eunji Yang, Jung-Ah Choi, June Young Chun, Jae-Ouk Kim, Cheol-Heui Yun, Cecil Czerkinsky, Man Ki Song
Potential use of cholera toxin (CT) as a mucosal vaccine adjuvant has been documented in a variety of animal models. However, native CT is highly toxic to be used as a mucosal adjuvant in humans. Here, we demonstrate a new approach to generate a mucosal adjuvant by replacing the B subunit of CT with HIV-1 Tat protein transduction domain (PTD), which efficiently delivers fusion proteins into the cell cytoplasm by unspecific binding to cell surface. We compared the adjuvanticity and toxicity of Tat PTD-CTA1-Tat PTD (TCTA1T) with those of CT...
2018: Journal of Immunology Research
S Steve Zhou, Salimatu Lukula, Cory Chiossone, Raymond W Nims, Donna B Suchmann, M Khalid Ijaz
Background: Prevention of infection with airborne pathogens and exposure to airborne particulates and aerosols (environmental pollutants and allergens) can be facilitated through use of disposable face masks. The effectiveness of such masks for excluding pathogens and pollutants is dependent on the intrinsic ability of the masks to resist penetration by airborne contaminants. This study evaluated the relative contributions of a mask, valve, and Micro Ventilator on aerosol filtration efficiency of a new N95 respiratory face mask...
March 2018: Journal of Thoracic Disease
Arwen F Altenburg, Stella E van Trierum, Erwin de Bruin, Dennis de Meulder, Carolien E van de Sandt, Fiona R M van der Klis, Ron A M Fouchier, Marion P G Koopmans, Guus F Rimmelzwaan, Rory D de Vries
The replication-deficient orthopoxvirus modified vaccinia virus Ankara (MVA) is a promising vaccine vector against various pathogens and has an excellent safety record. However, pre-existing vector-specific immunity is frequently suggested to be a drawback of MVA-based vaccines. To address this issue, mice were vaccinated with MVA-based influenza vaccines in the presence or absence of orthopoxvirus-specific immunity. Importantly, protective efficacy of an MVA-based influenza vaccine against a homologous challenge was not impaired in the presence of orthopoxvirus-specific pre-existing immunity...
April 24, 2018: Scientific Reports
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