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Anushka C Galasiti Kankanamalage, Yunjeong Kim, Vishnu C Damalanka, Athri D Rathnayake, Anthony R Fehr, Nurjahan Mehzabeen, Kevin P Battaile, Scott Lovell, Gerald H Lushington, Stanley Perlman, Kyeong-Ok Chang, William C Groutas
There are currently no approved vaccines or small molecule therapeutics available for the prophylaxis or treatment of Middle East Respiratory Syndrome coronavirus (MERS-CoV) infections. MERS-CoV 3CL protease is essential for viral replication; consequently, it is an attractive target that provides a potentially effective means of developing small molecule therapeutics for combatting MERS-CoV. We describe herein the structure-guided design and evaluation of a novel class of inhibitors of MERS-CoV 3CL protease that embody a piperidine moiety as a design element that is well-suited to exploiting favorable subsite binding interactions to attain optimal pharmacological activity and PK properties...
March 6, 2018: European Journal of Medicinal Chemistry
Angus Fayia Tengbeh, Luisa Enria, Elizabeth Smout, Thomas Mooney, Mike Callaghan, David Ishola, Bailah Leigh, Deborah Watson-Jones, Brian Greenwood, Heidi Larson, Shelley Lees
The 2014-2016 Ebola epidemic presented a challenging setting in which to carry out clinical trials. This paper reports findings from social science research carried out in Kambia, Northern Sierra Leone during first year of an Ebola vaccine trial (August 2015-July 2016). The social science team collected data through ethnographic observation, 42 in depth interviews; 4 life narratives; 200 exit interviews; 31 key informant interviews; and 8 focus group discussions with trial participants and community members not enrolled in the trial...
March 5, 2018: Social Science & Medicine
Teresa de Los Santos, Fayna Diaz-San Segundo, Luis L Rodriguez
Foot-and-mouth disease (FMD) continues to be the viral disease posing the greatest economic threat to agriculture. An unusually fast replication rate, extreme transmissibility, broad species tropism and antigenic diversity have made its etiologic agent, FMD virus, a difficult pathogen to defeat. Over the last 70 years, use of an inactivated virus vaccine has played a key role in disease control and eradication was possible in certain regions of the world. However, a rapidly changing environment, increased trade, population growth, international travel and migration, contribute to disease resurgence, challenging the capabilities of any available vaccine...
March 12, 2018: Current Opinion in Virology
Winnie Wing Yan Yuen, Albert Lee, Paul K S Chan, Lynn Tran, Erica Sayko
The present study is aimed at assessing the feasibility of delivering the HPV (human papillomavirus) vaccine to girls through a school-based program in Hong Kong, as well as to examine the facilitators and barriers associated with their participation. We approached 1,229 eligible girls aged 9 to 14 at eight schools in Hong Kong to join the program and then delivered the bivalent HPV vaccine at 0 and 6 months over the course of one school year. The students and their parents completed separate questionnaires to indicate their decision on whether or not to participate, and to assess their knowledge of cervical cancer and the HPV vaccine...
2018: PloS One
Andrea Cristine Koishi, Andréia Akemi Suzukawa, Camila Zanluca, Daria Elena Camacho, Guillermo Comach, Claudia Nunes Duarte Dos Santos
Zika virus (ZIKV) is an emerging arbovirus belonging to the genus flavivirus that comprises other important public health viruses, such as dengue (DENV) and yellow fever (YFV). In general, ZIKV infection is a self-limiting disease, however cases of Guillain-Barré syndrome and congenital brain abnormalities in newborn infants have been reported. Diagnosing ZIKV infection remains a challenge, as viral RNA detection is only applicable until a few days after the onset of symptoms. After that, serological tests must be applied, and, as expected, high cross-reactivity between ZIKV and other flavivirus serology is observed...
March 15, 2018: PLoS Neglected Tropical Diseases
Mary M Alleman, Rohit Chitale, Cara C Burns, Jane Iber, Naomi Dybdahl-Sissoko, Qi Chen, Djo-Roy Van Koko, Raimi Ewetola, Yogolelo Riziki, Hugo Kavunga-Membo, Cheikh Dah, Rija Andriamihantanirina
The last confirmed wild poliovirus (WPV) case in Democratic Republic of the Congo (DRC) had paralysis onset in December 2011 (1). DRC has had cases of vaccine-derived polioviruses (VDPVs) documented since 2004 (Table 1) (1-6). After an outbreak of 30 circulating VDPV type 2 (cVDPV2) cases during 2011-2012, only five VDPV2 cases were reported during 2013-2016 (Table 1) (1-6). VDPVs can emerge from oral poliovirus vaccine (OPV types 1, 2, or 3; Sabin) polioviruses that have genetically mutated resulting in reversion to neurovirulence...
March 16, 2018: MMWR. Morbidity and Mortality Weekly Report
Yefu Zhang, Meimei Ji, Jiaojiao Zou, Tong Yuan, Jing Deng, Lina Yang, Mingzhi Li, Hong Qin, Jihua Chen, Qian Lin
Left-behind children (LBC) are a unique population in China, whose numbers have increased dramatically in recent years. Most caregivers of left-behind children (CLBC) are grandparents who lack knowledge about proper nutrition and food practice, putting LBC at greater risk for malnutrition. A cluster randomized controlled trial was carried to assess the effectiveness of the conditional cash transfer (CCT) program. Forty rural villages from Fenghuang County and Pingjiang County of Hunan province were selected...
March 15, 2018: International Journal of Environmental Research and Public Health
Karen L Wozniak
The fungal pathogens Cryptococcus neoformans and Cryptococcus gattii can cause life-threatening infections in immune compromised and immune competent hosts. These pathogens enter the host via inhalation, and respiratory tract innate immune cells such as dendritic cells (DCs) are one of the first host cells they encounter. The interactions between Cryptococcus and innate immune cells play a critical role in the progression of disease in the host. This review will focus specifically on the interactions between Cryptococcus and dendritic cells (DCs), including recognition/processing by DCs, effects of immune mediators on DC recruitment and activity, and the potential for DC vaccination against cryptococcosis...
March 15, 2018: Journal of Fungi (Basel, Switzerland)
Jennifer S Evans, Guanghui Wu, David Selden, Hubert Buczkowski, Leigh Thorne, Anthony R Fooks, Ashley C Banyard
Lyssaviruses constitute a diverse range of viruses with the ability to cause fatal encephalitis known as rabies. Existing human rabies vaccines and post exposure prophylaxes (PEP) are based on inactivated preparations of, and neutralising antibody preparations directed against, classical rabies viruses, respectively. Whilst these prophylaxes are highly efficient at neutralising and preventing a productive infection with rabies virus, their ability to neutralise other lyssaviruses is thought to be limited. The remaining 15 virus species within the lyssavirus genus have been divided into at least three phylogroups that generally predict vaccine protection...
March 15, 2018: Viruses
Larisa J Geskin, James J Damiano, Christina C Patrone, Lisa H Butterfield, John M Kirkwood, Louis D Falo
In the current era of checkpoint inhibitors, some patients with metastatic melanoma have shown a significant improvement in survival. However, optimization of immunotherapy is an ongoing effort. Monocyte-derived dendritic cell (MODC) vaccines have been shown in clinical trials to be safe and capable of inducing tumor-specific immunity as well as occasional objective clinical responses. Here, we conducted a three-arm pilot clinical study in 15 patients with metastatic melanoma to evaluate three types of MODC vaccines, differing only by strategies of tumor antigen delivery...
March 14, 2018: Melanoma Research
Christine Juergens, James Trammel, Yasuko Shoji, Scott Patterson, Wendy Watson, Chris Webber, William C Gruber, Daniel A Scott, Beate Schmoele-Thoma
Injection site reactions (ISRs; redness, swelling and pain) commonly occur within 1-2 days after vaccination. After administration of toxoid vaccines including diphtheria toxoid, a later onset of ISRs has also been observed. As the serotype capsular polysaccharides in the 13-valent pneumococcal conjugate vaccine (PCV13) are conjugated to cross-reactive material 197 (CRM197 ), a nontoxic variant of diphtheria toxin, the onset of ISRs over 14 days was explored in 8 adult studies with 19 cohorts. Subjects received PCV13 with aluminum phosphate (AlPO4 , n = 5667) or without AlPO4 (n = 304); 109 subjects received 23-valent pneumococcal polysaccharide vaccine (PPSV23)...
March 15, 2018: Human Vaccines & Immunotherapeutics
A W Dretler, N G Rouphael, D S Stephens
The control of meningitis, meningococcemia and other infections caused by Neisseria meningitidis is a significant global health challenge. Substantial progress has occurred in the last twenty years in meningococcal vaccine development and global implementation. Meningococcal protein-polysaccharide conjugate vaccines to serogroups A, C, W, and Y (modeled after the Haemophilus influenzae b conjugate vaccines) provide better duration of protection and immunologic memory, and overcome weak immune responses in infants and young children and hypo-responsive to repeated vaccine doses seen with polysaccharide vaccines...
March 15, 2018: Human Vaccines & Immunotherapeutics
Sevim Meşe, Aysun Uyanik, Alev Özakay, Serdar Öztürk, Selim Badur
Human influenza is predominantly caused by influenza A virus (IAV) - A/H1N1 and/or A/H3N2 - and influenza B virus (IBV) - B/Victoria and/or B/Yamagata, which co-circulate each season. Influenza surveillance provides important information on seasonal disease burden and circulation, and vaccine content for the following season. To study the circulating influenza subtypes/lineages in western Turkey. Community-based sentinel surveillance results during 2003-2016 (weeks 40-20 each season; but week 21, 2009 through week 20, 2010 during the pandemic) were analyzed...
March 15, 2018: Human Vaccines & Immunotherapeutics
Raches Ella, Radhika Bobba, Sanjay Muralidhar, Sudhir Babji, Krishna Mohan Vadrevu, Maharaj Kishan Bhan
BACKGROUND: The World Health Organization recommends that rotavirus vaccines should be included in all national immunization programs. Some currently licensed oral rotavirus vaccines contain a buffering agent (either as part of a ready-to-use liquid formulation or added during reconstitution) to reduce possible degradation of the vaccine virus in the infant gut, which poses several programmatic challenges (the large dose volume or the reconstitution requirement) during vaccine administration...
March 15, 2018: Human Vaccines & Immunotherapeutics
Scott Vuocolo, Paul Balmer, William C Gruber, Kathrin U Jansen, Annaliesa S Anderson, John L Perez, Laura J York
Routine prophylactic vaccination and mass vaccination strategies have been used to control both endemic and epidemic disease caused by Neisseria meningitidis globally. This review discusses real-world examples of these vaccination strategies, their implementation, and outcomes of these efforts, with the overall goal of providing insights on how to achieve optimal control of meningococcal disease through vaccination in varied settings. Tailoring immunization programs to fit the needs of the target population has the potential to optimally reduce disease incidence...
March 15, 2018: Human Vaccines & Immunotherapeutics
Martina Gobec, Tihomir Tomašič, Adela Štimac, Ruža Frkanec, Jurij Trontelj, Marko Anderluh, Irena Mlinaric-Rascan, Žiga Jakopin
Muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan, has long been known as the smallest fragment possessing adjuvant activity, on the basis of its agonistic action on the nucleotide-binding oligomerization domain-containing protein 2 (NOD2). There is a pressing need for novel adjuvants and NOD2 agonists provide an untapped source of potential candidates. Here, we report the design, synthesis and characterization of a series of novel acyl tripeptides. A pivotal structural element for molecular recognition by NOD2 has been identified, culminating in the discovery of compound 9, the most potent desmuramylpeptide NOD2 agonist to date...
March 15, 2018: Journal of Medicinal Chemistry
Cinta Moraleda, Rachid Benmessaoud, Jessica Esteban, Yuly López, Hassan Alami, Amina Barkat, Tligui Houssain, Meryem Kabiri, Rachid Bezad, Saad Chaacho, Lola Madrid, Jordi Vila, Carmen Muñoz-Almagro, Jordi Bosch, Sara M Soto, Quique Bassat
PURPOSE: Group B streptococcus (GBS) is an important cause of neonatal sepsis worldwide. Data on the prevalence of maternal GBS colonization, risk factors for carriage, antibiotic susceptibility and circulating serotypes are necessary to tailor adequate locally relevant public health policies. METHODOLOGY: A prospective study including pregnant women and their newborns was conducted between March and July 2013 in Morocco. We collected clinical data and vagino-rectal and urine samples from the recruited pregnant women, together with the clinical characteristics of, and body surface samples from, their newborns...
March 15, 2018: Journal of Medical Microbiology
S K Abdrakhmanov, S B Tyulegenov, F I Korennoy, A A Sultanov, I I Sytnik, K K Beisembaev, A A Bainiyazov, A E Munsey, A M Perez, K VanderWaal
Foot-and-mouth disease (FMD) poses a significant obstacle to international trade and economic development, and for that reason, FMD prevention, control and eradication are major goals guiding animal health policy in most countries. The purpose of this study was to conduct a retrospective spatiotemporal analysis of FMD outbreaks among livestock in the Republic of Kazakhstan (RK) from 1955 to 2013. During that time, several FMD control strategies were implemented in RK, which culminated with the World Organization for Animal Health (OIE) recognition of RK as a country that is FMD-free with partial vaccination (2015)...
March 15, 2018: Transboundary and Emerging Diseases
Nongluk Sriwilaijaroen, Shin-Ichi Nakakita, Sachiko Kondo, Hirokazu Yagi, Koichi Kato, Takeomi Murata, Hiroaki Hiramatsu, Toshio Kawahara, Yohei Watanabe, Yasushi Kanai, Takao Ono, Jun Hirabayashi, Kazuhiko Matsumoto, Yasuo Suzuki
The rapidly evolvable influenza A virus has caused pandemics linked to millions of deaths in the past century. Influenza A viruses are categorized by H (hemagglutinin; HA) and N (neuraminidase; NA) proteins expressed on the viral envelope surface. Analyses of past pandemics suggest that the HA gene segment comes from a nonhuman virus, which is then introduced into an immunologically naïve human population with potentially devastating consequences. As a prerequisite for infection, the nonhuman HA molecules of H1-H16 viruses must be able to bind to specific sialyl receptors on the host cell surface along the human respiratory tract...
March 15, 2018: FEBS Journal
Patrick A Ott, Zhuting Hu, Derin B Keskin, Sachet A Shukla, Jing Sun, David J Bozym, Wandi Zhang, Adrienne Luoma, Anita Giobbie-Hurder, Lauren Peter, Christina Chen, Oriol Olive, Todd A Carter, Shuqiang Li, David J Lieb, Thomas Eisenhaure, Evisa Gjini, Jonathan Stevens, William J Lane, Indu Javeri, Kaliappanadar Nellaiappan, Andres M Salazar, Heather Daley, Michael Seaman, Elizabeth I Buchbinder, Charles H Yoon, Maegan Harden, Niall Lennon, Stacey Gabriel, Scott J Rodig, Dan H Barouch, Jon C Aster, Gad Getz, Kai Wucherpfennig, Donna Neuberg, Jerome Ritz, Eric S Lander, Edward F Fritsch, Nir Hacohen, Catherine J Wu
This corrects the article DOI: 10.1038/nature22991.
March 14, 2018: Nature
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