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Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. Age (>60 years) is a significant risk factor for developing severe COVID-19. To better understand the host response of the aged airway epithelium to SARS-CoV-2 infection, we performed an in vitro study using primary human bronchial epithelial cells from donors >67 years of age differentiated on an air–liquid interface culture. We demonstrate that SARS-CoV-2 infection leads to early induction of a proinflammatory response and a delayed interferon response. In addition, we observed changes in the genes and pathways associated with cell death and senescence throughout infection. In summary, our study provides new and important insights into the temporal kinetics of the airway epithelial innate immune response to SARS-CoV-2 in older individuals.
Bharathiraja Subramaniyan; Jason L. Larabee; Manish Bodas; Andrew R. Moore; Anthony W. G. Burgett; Dean A. Myers; Constantin Georgescu; Jonathan D. Wren; James F. Papin; Matthew S. Walters. Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals. Viruses 2021, 13, 1603 .
AMA StyleBharathiraja Subramaniyan, Jason L. Larabee, Manish Bodas, Andrew R. Moore, Anthony W. G. Burgett, Dean A. Myers, Constantin Georgescu, Jonathan D. Wren, James F. Papin, Matthew S. Walters. Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals. Viruses. 2021; 13 (8):1603.
Chicago/Turabian StyleBharathiraja Subramaniyan; Jason L. Larabee; Manish Bodas; Andrew R. Moore; Anthony W. G. Burgett; Dean A. Myers; Constantin Georgescu; Jonathan D. Wren; James F. Papin; Matthew S. Walters. 2021. "Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals." Viruses 13, no. 8: 1603.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains a pandemic. Severe disease is associated with dysfunction of multiple organs, but some infected cells do not express ACE2, the canonical entry receptor for SARS-CoV-2. Here, we report that the C-type lectin receptor L-SIGN interacted in a Ca2+-dependent manner with high-mannose–type N-glycans on the SARS-CoV-2 spike protein. We found that L-SIGN was highly expressed on human liver sinusoidal endothelial cells (LSECs) and lymph node lymphatic endothelial cells but not on blood endothelial cells. Using high-resolution confocal microscopy imaging, we detected SARS-CoV-2 viral proteins within the LSECs from liver autopsy samples from patients with COVID-19. We found that both pseudo-typed virus enveloped with SARS-CoV-2 spike protein and authentic SARS-CoV-2 virus infected L-SIGN–expressing cells relative to control cells. Moreover, blocking L-SIGN function reduced CoV-2–type infection. These results indicate that L-SIGN is a receptor for SARS-CoV-2 infection. LSECs are major sources of the clotting factors vWF and factor VIII (FVIII). LSECs from liver autopsy samples from patients with COVID-19 expressed substantially higher levels of vWF and FVIII than LSECs from uninfected liver samples. Our data demonstrate that L-SIGN is an endothelial cell receptor for SARS-CoV-2 that may contribute to COVID-19–associated coagulopathy.
Yuji Kondo; Jason L. Larabee; Liang Gao; Huiping Shi; Bojing Shao; Christopher M. Hoover; J. Michael McDaniel; Yen-Chun Ho; Robert Silasi-Mansat; Stephanie A. Archer-Hartmann; Parastoo Azadi; R. Sathish Srinivasan; Alireza R. Rezaie; Alain Borczuk; Jeffrey C. Laurence; Florea Lupu; Jasimuddin Ahamed; Rodger P. McEver; James F. Papin; Zhongxin Yu; Lijun Xia. L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus. JCI Insight 2021, 6, 1 .
AMA StyleYuji Kondo, Jason L. Larabee, Liang Gao, Huiping Shi, Bojing Shao, Christopher M. Hoover, J. Michael McDaniel, Yen-Chun Ho, Robert Silasi-Mansat, Stephanie A. Archer-Hartmann, Parastoo Azadi, R. Sathish Srinivasan, Alireza R. Rezaie, Alain Borczuk, Jeffrey C. Laurence, Florea Lupu, Jasimuddin Ahamed, Rodger P. McEver, James F. Papin, Zhongxin Yu, Lijun Xia. L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus. JCI Insight. 2021; 6 (14):1.
Chicago/Turabian StyleYuji Kondo; Jason L. Larabee; Liang Gao; Huiping Shi; Bojing Shao; Christopher M. Hoover; J. Michael McDaniel; Yen-Chun Ho; Robert Silasi-Mansat; Stephanie A. Archer-Hartmann; Parastoo Azadi; R. Sathish Srinivasan; Alireza R. Rezaie; Alain Borczuk; Jeffrey C. Laurence; Florea Lupu; Jasimuddin Ahamed; Rodger P. McEver; James F. Papin; Zhongxin Yu; Lijun Xia. 2021. "L-SIGN is a receptor on liver sinusoidal endothelial cells for SARS-CoV-2 virus." JCI Insight 6, no. 14: 1.
Respiratory syncytial virus (RSV) is the major viral respiratory pathogen for human infants and children. Despite a severe global burden incurred by annual RSV epidemics, there is no licensed RSV vaccine. We have developed an RSV vaccine from a human RSV strain from which the gene for the viral M protein has been deleted (“Mnull RSV”). RSV infects airway cells and produces each of its proteins. The M protein is responsible for reassembling the various other synthesized viral proteins into new, intact virus. In the absence of the M protein, therefore, reassembly does not occur, and the Mnull RSV does not replicate. We vaccinated 2-week old infant baboons with Mnull RSV either intranasally (IN) or directly into the lung (intratracheal, or IT), then infected these animals by inoculating human RSV directly into the lung. IN vaccination induced inconsistent serum RSV neutralizing antibody (NA) responses, but provided moderate reductions in respiratory rates, overall signs of illness and viral replication in bronchoalveolar lavage (BAL) fluid following infection. Intratracheal vaccination induced much stronger RSV NA responses, which persisted for at least 4–6 months. Following RSV infection, animals vaccinated by the IT route had much greater reductions in tachypnea and work of breathing than animals vaccinated IN, and had undetectable amounts of virus in BAL fluids. These results support the further development of IT Mnull RSV vaccination to reduce the impact of RSV infection in humans.
Vadim Ivanov; Antonius G.P. Oomens; James F. Papin; Rachel Staats; Darlene N. Reuter; Zhongxin Yu; Pedro A. Piedra; Robert C. Wellliver. Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection. Vaccine 2021, 39, 4063 -4071.
AMA StyleVadim Ivanov, Antonius G.P. Oomens, James F. Papin, Rachel Staats, Darlene N. Reuter, Zhongxin Yu, Pedro A. Piedra, Robert C. Wellliver. Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection. Vaccine. 2021; 39 (30):4063-4071.
Chicago/Turabian StyleVadim Ivanov; Antonius G.P. Oomens; James F. Papin; Rachel Staats; Darlene N. Reuter; Zhongxin Yu; Pedro A. Piedra; Robert C. Wellliver. 2021. "Intranasal and intrapulmonary vaccination with an M protein-deficient respiratory syncytial virus (RSV) vaccine improves clinical signs and reduces viral replication in infant baboons after an RSV challenge infection." Vaccine 39, no. 30: 4063-4071.
The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd protection and control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) from the full-length spike (S) protein that is stable in the prefusion conformation. NVX-CoV2373 S form 27.2-nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicit high titer anti-S IgG that blocks hACE2 receptor binding, neutralize virus, and protects against SARS-CoV-2 challenge with no evidence of vaccine-associated enhanced respiratory disease. NVX-CoV2373 also elicits multifunctional CD4+ and CD8+ T cells, CD4+ follicular helper T cells (Tfh), and antigen-specific germinal center (GC) B cells in the spleen. In baboons, low-dose levels of NVX-CoV2373 with Matrix-M was also highly immunogenic and elicited high titer anti-S antibodies and functional antibodies that block S-protein binding to hACE2 and neutralize virus infection and antigen-specific T cells. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2373 with Matrix-M (NCT04368988).
Jing-Hui Tian; Nita Patel; Robert Haupt; Haixia Zhou; Stuart Weston; Holly Hammond; James Logue; Alyse D. Portnoff; James Norton; Mimi Guebre-Xabier; Bin Zhou; Kelsey Jacobson; Sonia Maciejewski; Rafia Khatoon; Malgorzata Wisniewska; Will Moffitt; Stefanie Kluepfel-Stahl; Betty Ekechukwu; James Papin; Sarathi Boddapati; C. Jason Wong; Pedro A. Piedra; Matthew B. Frieman; Michael J. Massare; Louis Fries; Karin Lövgren Bengtsson; Linda Stertman; Larry Ellingsworth; Gregory Glenn; Gale Smith. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nature Communications 2021, 12, 1 -14.
AMA StyleJing-Hui Tian, Nita Patel, Robert Haupt, Haixia Zhou, Stuart Weston, Holly Hammond, James Logue, Alyse D. Portnoff, James Norton, Mimi Guebre-Xabier, Bin Zhou, Kelsey Jacobson, Sonia Maciejewski, Rafia Khatoon, Malgorzata Wisniewska, Will Moffitt, Stefanie Kluepfel-Stahl, Betty Ekechukwu, James Papin, Sarathi Boddapati, C. Jason Wong, Pedro A. Piedra, Matthew B. Frieman, Michael J. Massare, Louis Fries, Karin Lövgren Bengtsson, Linda Stertman, Larry Ellingsworth, Gregory Glenn, Gale Smith. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice. Nature Communications. 2021; 12 (1):1-14.
Chicago/Turabian StyleJing-Hui Tian; Nita Patel; Robert Haupt; Haixia Zhou; Stuart Weston; Holly Hammond; James Logue; Alyse D. Portnoff; James Norton; Mimi Guebre-Xabier; Bin Zhou; Kelsey Jacobson; Sonia Maciejewski; Rafia Khatoon; Malgorzata Wisniewska; Will Moffitt; Stefanie Kluepfel-Stahl; Betty Ekechukwu; James Papin; Sarathi Boddapati; C. Jason Wong; Pedro A. Piedra; Matthew B. Frieman; Michael J. Massare; Louis Fries; Karin Lövgren Bengtsson; Linda Stertman; Larry Ellingsworth; Gregory Glenn; Gale Smith. 2021. "SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice." Nature Communications 12, no. 1: 1-14.
The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2 nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).
Jing-Hui Tian; Nita Patel; Robert Haupt; Haixia Zhou; Stuart Weston; Holly Hammond; James Logue; Alyse Pornoff; James Norton; Mimi Guebre-Xabier; Bin Zhou; Kelsey Jacobson; Sonia Maciejewski; Rafia Khatoon; Malgorzata Wisniewska; Will Moffitt; Stefanie Kluefel-Stahl; Betty Ekechukwu; James Papin; Sarathi Boddapati; C. Jason Wong; Pedro Piedra; Matthew Frieman; Michael Massare; Louis Fries; Karin Lovgren Bengtsson; Linda Stertman; Larry Ellingsworth; Gregory Glenn; Gale Smith. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. 2020, 1 .
AMA StyleJing-Hui Tian, Nita Patel, Robert Haupt, Haixia Zhou, Stuart Weston, Holly Hammond, James Logue, Alyse Pornoff, James Norton, Mimi Guebre-Xabier, Bin Zhou, Kelsey Jacobson, Sonia Maciejewski, Rafia Khatoon, Malgorzata Wisniewska, Will Moffitt, Stefanie Kluefel-Stahl, Betty Ekechukwu, James Papin, Sarathi Boddapati, C. Jason Wong, Pedro Piedra, Matthew Frieman, Michael Massare, Louis Fries, Karin Lovgren Bengtsson, Linda Stertman, Larry Ellingsworth, Gregory Glenn, Gale Smith. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice. . 2020; ():1.
Chicago/Turabian StyleJing-Hui Tian; Nita Patel; Robert Haupt; Haixia Zhou; Stuart Weston; Holly Hammond; James Logue; Alyse Pornoff; James Norton; Mimi Guebre-Xabier; Bin Zhou; Kelsey Jacobson; Sonia Maciejewski; Rafia Khatoon; Malgorzata Wisniewska; Will Moffitt; Stefanie Kluefel-Stahl; Betty Ekechukwu; James Papin; Sarathi Boddapati; C. Jason Wong; Pedro Piedra; Matthew Frieman; Michael Massare; Louis Fries; Karin Lovgren Bengtsson; Linda Stertman; Larry Ellingsworth; Gregory Glenn; Gale Smith. 2020. "SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice." , no. : 1.
Zika virus remains a worldwide health threat, with outbreaks still occurring in the Americas. While mosquitos are the primary vector for the spread of the virus, sexual transmission of Zika virus is also a significant means of infection, especially in terms of passage from an infected to an uninfected partner. While sexual transmission has been documented in humans, and male-to-female transmission has been reported in mice, ours is the first study in nonhuman primates to demonstrate infection via vaginal deposition of Zika virus-infected semen. The latter is important since a recent publication indicated that human semen inhibited, in a laboratory setting, Zika virus infection of reproductive tissues. We also found that compared to the French Polynesian isolate, the Puerto Rican Zika virus isolate led to greater spread throughout the body, particularly in reproductive tissues. The American isolates of Zika virus appear to have acquired mutations that increase their efficacy.
Sunam Gurung; Hugh Nadeau; Marta Maxted; Jamie Peregrine; Darlene Reuter; Abby Norris; Rodney Edwards; Kimberly Hyatt; Krista Singleton; James F. Papin; Dean A. Myers. Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons. Journal of Virology 2020, 94, 1 .
AMA StyleSunam Gurung, Hugh Nadeau, Marta Maxted, Jamie Peregrine, Darlene Reuter, Abby Norris, Rodney Edwards, Kimberly Hyatt, Krista Singleton, James F. Papin, Dean A. Myers. Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons. Journal of Virology. 2020; 94 (11):1.
Chicago/Turabian StyleSunam Gurung; Hugh Nadeau; Marta Maxted; Jamie Peregrine; Darlene Reuter; Abby Norris; Rodney Edwards; Kimberly Hyatt; Krista Singleton; James F. Papin; Dean A. Myers. 2020. "Maternal Zika Virus (ZIKV) Infection following Vaginal Inoculation with ZIKV-Infected Semen in Timed-Pregnant Olive Baboons." Journal of Virology 94, no. 11: 1.
Background Schistosomiasis continues to inflict significant morbidity and mortality in the tropical and subtropical regions of the world. The disease endemicity overlaps with the transmission of other parasitic diseases. Despite the ubiquity of polyparasitism in tropical regions, particularly in rural communities, little is known about the impact of multiple helminth infections on disease progression. In this pilot study, we describe the influence of chronic Trichuris trichiura infection on Schistosoma mansoni egg-induced hepatopathology in infected baboons. Methods Baboons with or without underlying whipworm infection were challenged with S. mansoni cercariae to establish schistosomiasis. Adult S. mansoni worms were recovered by perfusion and enumerated, hepatic granulomas were quantified via light microscopy, and transcriptional profiling of tissues were completed using RNA sequencing technologies. Results Co-infection with both S. mansoni and T. trichiura resulted in higher female schistosome worm burden and significantly larger liver granuloma sizes. Systems biology analyses of peripheral blood mononuclear cells (PBMC) revealed pathways associated with increased liver damage in co-infected baboons. Conclusions Underlying chronic whipworm infection intensified schistosome egg-induced liver pathology in infected baboons. RNA-Seq analysis provided insight into pathways associated with increased liver damage, corroborating histological findings.
Loc Le; Sabiha Khatoon; Paola Jiménez; Christopher Peterson; Rebecca Kernen; Weidong Zhang; Adebayo J. Molehin; Samra Lazarus; Justin Sudduth; Jordan May; Souvik Karmakar; Juan U. Rojo; Gul Ahmad; Workineh Torben; David Carey; Roman F. Wolf; James F. Papin; Afzal A. Siddiqui. Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates. Parasites & Vectors 2020, 13, 109 -7.
AMA StyleLoc Le, Sabiha Khatoon, Paola Jiménez, Christopher Peterson, Rebecca Kernen, Weidong Zhang, Adebayo J. Molehin, Samra Lazarus, Justin Sudduth, Jordan May, Souvik Karmakar, Juan U. Rojo, Gul Ahmad, Workineh Torben, David Carey, Roman F. Wolf, James F. Papin, Afzal A. Siddiqui. Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates. Parasites & Vectors. 2020; 13 (1):109-7.
Chicago/Turabian StyleLoc Le; Sabiha Khatoon; Paola Jiménez; Christopher Peterson; Rebecca Kernen; Weidong Zhang; Adebayo J. Molehin; Samra Lazarus; Justin Sudduth; Jordan May; Souvik Karmakar; Juan U. Rojo; Gul Ahmad; Workineh Torben; David Carey; Roman F. Wolf; James F. Papin; Afzal A. Siddiqui. 2020. "Chronic whipworm infection exacerbates Schistosoma mansoni egg-induced hepatopathology in non-human primates." Parasites & Vectors 13, no. 1: 109-7.
Pertussis continues to cause considerable infant mortality world-wide, which could be addressed in part by passive immunization strategies. Antibody hu1B7 is a candidate therapeutic that potently neutralizes pertussis toxin in vitro, prevents leukocytosis in mice and treats established disease in weanling baboons as part of an antibody cocktail. Here, we evaluated the potential for hu1B7 and an extended half-life hu1B7 variant to prevent death, leukocytosis and other clinical symptoms in a newborn baboon model that mimics many aspects of human disease. We administered a single antibody dose to newborn baboons five weeks prior to experimental infection. While all animals were heavily colonized with Bordetella pertussis, prophylaxed animals showed significantly greater survival (P < 0.005), delayed and suppressed leukocytosis (P < 0.01) and enhanced clinical outcomes, including coughing (P < 0.01), as compared to controls. Together, this work demonstrates that a single neutralizing anti-PTx antibody is sufficient to prevent clinical pertussis symptoms.
Annalee W. Nguyen; Andrea M. DiVenere; James F. Papin; Sheila Connelly; Michael Kaleko; Jennifer A. Maynard. Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons. Science Advances 2020, 6, eaay9258 .
AMA StyleAnnalee W. Nguyen, Andrea M. DiVenere, James F. Papin, Sheila Connelly, Michael Kaleko, Jennifer A. Maynard. Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons. Science Advances. 2020; 6 (6):eaay9258.
Chicago/Turabian StyleAnnalee W. Nguyen; Andrea M. DiVenere; James F. Papin; Sheila Connelly; Michael Kaleko; Jennifer A. Maynard. 2020. "Neutralization of pertussis toxin by a single antibody prevents clinical pertussis in neonatal baboons." Science Advances 6, no. 6: eaay9258.
ZIKV infection is associated with fetal microcephaly and other malformations. While Aedes sp. of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. It is critical to establish NHP models of vertical transfer of ZIKV that recapitulate human ZIKV pathogenesis. We hypothesized that vaginal deposition of ZIKV infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Timed pregnant baboons (n=6) were inoculated via vaginal deposition of baboon semen containing 106ffu ZIKV (n=3, French Polynesian isolate:H/PF/2013, n=3 Puerto Rican isolate:PRVABC59) at mid-gestation (86-95 days gestation [dG]; term 183dG) on day (d) 0 (all dams), then at 7 day intervals through three weeks. Maternal blood, saliva and cervico-vaginal washes (CVW) were obtained at select days post-inoculation. Animals were euthanized at 28 days post initial inoculation (dpi; n=5) or 39 dpi (n=1) and tissues collected. Viremia was achieved in 3/3 FP ZIKV and 2/3 PR ZIKV dams. ZIKV RNA was detected in CVW (5/6 dams;). ZIKV RNA was detected in lymph nodes, but not ovary, uterus, cervix or vagina in the FP ZIKV dams; ZIKV RNA was detected in uterus, vagina and lymph nodes of PR infected dams. Placenta were ZIKV RNA negative in the FP infected dams while were positive in 2/3 PR infected dam. We conclude that ZIKV infected semen is an effective means of transmission during pregnancy in primates. The PR isolate lead to a broader dissemination to tissues, vs the FP strain.
Sunam Gurung; Hugh Nadeau; Marta Maxted; Jamie Peregrine; Darlene N. Reuter; Abby Norris; Rodney K Edwards; Kimberly Hyatt; Krista Singleton; James Frederick Papin; Dean A. Myers. MATERNAL ZIKA VIRUS (ZIKV) INFECTION FOLLOWING VAGINAL INOCULATION WITH ZIKV-INFECTED SEMEN IN THE TIMED-PREGNANT OLIVE BABOON. 2020, 1 .
AMA StyleSunam Gurung, Hugh Nadeau, Marta Maxted, Jamie Peregrine, Darlene N. Reuter, Abby Norris, Rodney K Edwards, Kimberly Hyatt, Krista Singleton, James Frederick Papin, Dean A. Myers. MATERNAL ZIKA VIRUS (ZIKV) INFECTION FOLLOWING VAGINAL INOCULATION WITH ZIKV-INFECTED SEMEN IN THE TIMED-PREGNANT OLIVE BABOON. . 2020; ():1.
Chicago/Turabian StyleSunam Gurung; Hugh Nadeau; Marta Maxted; Jamie Peregrine; Darlene N. Reuter; Abby Norris; Rodney K Edwards; Kimberly Hyatt; Krista Singleton; James Frederick Papin; Dean A. Myers. 2020. "MATERNAL ZIKA VIRUS (ZIKV) INFECTION FOLLOWING VAGINAL INOCULATION WITH ZIKV-INFECTED SEMEN IN THE TIMED-PREGNANT OLIVE BABOON." , no. : 1.
Zika virus (ZIKV) is an emerging flavivirus spread through mosquitoes and sexual contact. ZIKV infection during pregnancy can lead to severe fetal outcomes, including miscarriage, fetal death, preterm birth, intrauterine growth restriction, and fetal microcephaly, collectively known as congenital Zika syndrome. Therefore, it is important to understand how this virus spreads, as well as the resulting pathogenesis in translational animal models that faithfully mimic ZIKV infection in humans. Such models will contribute to the future development of efficient therapeutics and prevention mechanisms. Through our previous work in olive baboons, we developed a nonhuman primate model that is permissive to ZIKV infection and transfers the virus vertically from mother to fetus, modeling human observations. The present study contributes to understanding of ZIKV infection in male baboon reproductive tissues and begins to elucidate how this may affect fertility, reproductive capacity, and sexual transmission of the virus.
Jamie Peregrine; Sunam Gurung; Mark C. Lindgren; Sanam Husain; Michael T. Zavy; Dean A. Myers; James F. Papin. Zika Virus Infection, Reproductive Organ Targeting, and Semen Transmission in the Male Olive Baboon. Journal of Virology 2019, 94, 1 .
AMA StyleJamie Peregrine, Sunam Gurung, Mark C. Lindgren, Sanam Husain, Michael T. Zavy, Dean A. Myers, James F. Papin. Zika Virus Infection, Reproductive Organ Targeting, and Semen Transmission in the Male Olive Baboon. Journal of Virology. 2019; 94 (1):1.
Chicago/Turabian StyleJamie Peregrine; Sunam Gurung; Mark C. Lindgren; Sanam Husain; Michael T. Zavy; Dean A. Myers; James F. Papin. 2019. "Zika Virus Infection, Reproductive Organ Targeting, and Semen Transmission in the Male Olive Baboon." Journal of Virology 94, no. 1: 1.
Globally, human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory infection in infants and young children. There are no licensed vaccines despite the high worldwide disease burden. RSV fusion (F) glycoprotein vaccine is the most advanced candidate for maternal immunization. In this report, a baboon maternal immunization model was used to assess the immunogenicity and protection of infants against pulmonary challenge with human RSV/A. Vaccination in the third trimester produced high anti-RSV F IgG titers and virus-neutralizing antibodies. Infants born to immunized females had high levels of serum RSV antibodies that were comparable to maternal levels at birth and persisted for over 50 days with a half-life of 14–24 days. Furthermore, infants from immunized females and challenged with RSV/A were healthy, developed less severe disease, and had only mild pulmonary inflammatory changes whereas infants born to non-vaccinated females developed more severe disease with marked to moderate interstitial pneumonia, pulmonary edema, and bronchiolar obstruction. These results support the further development of the RSV F vaccine for maternal immunization.
Robert C. Welliver; James F. Papin; Alisha Preno; Vadim Ivanov; Jing-Hui Tian; Hanxin Lu; Mimi Guebre-Xabier; David Flyer; Michael J. Massare; Greg Glenn; Larry Ellingsworth; Gale Smith. Maternal immunization with RSV fusion glycoprotein vaccine and substantial protection of neonatal baboons against respiratory syncytial virus pulmonary challenge. Vaccine 2019, 38, 1258 -1270.
AMA StyleRobert C. Welliver, James F. Papin, Alisha Preno, Vadim Ivanov, Jing-Hui Tian, Hanxin Lu, Mimi Guebre-Xabier, David Flyer, Michael J. Massare, Greg Glenn, Larry Ellingsworth, Gale Smith. Maternal immunization with RSV fusion glycoprotein vaccine and substantial protection of neonatal baboons against respiratory syncytial virus pulmonary challenge. Vaccine. 2019; 38 (5):1258-1270.
Chicago/Turabian StyleRobert C. Welliver; James F. Papin; Alisha Preno; Vadim Ivanov; Jing-Hui Tian; Hanxin Lu; Mimi Guebre-Xabier; David Flyer; Michael J. Massare; Greg Glenn; Larry Ellingsworth; Gale Smith. 2019. "Maternal immunization with RSV fusion glycoprotein vaccine and substantial protection of neonatal baboons against respiratory syncytial virus pulmonary challenge." Vaccine 38, no. 5: 1258-1270.
Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to as Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and non-human primates (NHPs). In macaques, fetal CZS outcomes from maternal ZIKV infection range from none to significant. In the present study we develop the olive baboon (Papio anubis), as a model for vertical transfer of ZIKV during pregnancy. Four mid-gestation, timed-pregnant baboons were inoculated with the French Polynesian ZIKV isolate (104 ffu). This study specifically focused on the acute phase of vertical transfer. Dams were terminated at 7 days post infection (dpi; n = 1), 14 dpi (n = 2) and 21 dpi (n = 1). All dams exhibited mild to moderate rash and conjunctivitis. Viremia peaked at 5–7 dpi with only one of three dams remaining mildly viremic at 14 dpi. An anti-ZIKV IgM response was observed by 14 dpi in all three dams studied to this stage, and two dams developed a neutralizing IgG response by either 14 dpi or 21 dpi, the latter included transfer of the IgG to the fetus (cord blood). A systemic inflammatory response (increased IL2, IL6, IL7, IL15, IL16) was observed in three of four dams. Vertical transfer of ZIKV to the placenta was observed in three pregnancies (n = 2 at 14 dpi and n = 1 at 21 dpi) and ZIKV was detected in fetal tissues in two pregnancies: one associated with fetal death at ~14 dpi, and the other in a viable fetus at 21 dpi. ZIKV RNA was detected in the fetal cerebral cortex and other tissues of both of these fetuses. In the fetus studied at 21 dpi with vertical transfer of virus to the CNS, the frontal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, disorganized migration of immature neurons to the cortical layers, and signs of pathology in immature oligodendrocytes. In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL6 expression. Of interest, in one fetus examined at 14 dpi without detection of ZIKV RNA in brain and other fetal tissues, increased neuroinflammation (IL6 and microglia) was observed in the cortex. Although the placenta of the 14 dpi dam with fetal death showed considerable pathology, only minor pathology was noted in the other three placentas. ZIKV was detected immunohistochemically in two placentas (14 dpi) and one placenta at 21 dpi but not at 7 dpi. This is the first study to examine the early events of vertical transfer of ZIKV in a NHP infected at mid-gestation. The baboon thus represents an additional NHP as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs. Zika virus is endemic in the Americas, primarily spread through mosquitos and sexual contact. Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome (CZS), with the most severe pathology being fetal microcephaly. Developing model organisms that faithfully recreate Zika infection in humans is critical for future development of treatments and preventions. In our present study, we infected Olive baboons at mid-gestation with Zika virus and studied the acute period of viremia and transfer of Zika virus to the fetus during the first three weeks after infection to better understand the timing and mechanisms of transfer of ZIKV across the placenta, leading to CZS. We observed Zika virus transfer to fetuses resulting in fetal death in one pregnancy and in a second pregnancy, significant damage to the frontal cortex of the fetal brain at a critical period of neurodevelopment in primates. Thus, the baboon provides a promising new non-human primate model to further compare and contrast the consequences of Zika virus infection in pregnancy to humans and other non-human primates.
Sunam Gurung; Nicole Reuter; Alisha Preno; Jamie Dubaut; Hugh Nadeau; Kimberly Hyatt; Krista Singleton; Ashley Martin; W. Tony Parks; James F. Papin; Dean A. Myers. Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. PLOS Pathogens 2019, 15, e1007507 .
AMA StyleSunam Gurung, Nicole Reuter, Alisha Preno, Jamie Dubaut, Hugh Nadeau, Kimberly Hyatt, Krista Singleton, Ashley Martin, W. Tony Parks, James F. Papin, Dean A. Myers. Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. PLOS Pathogens. 2019; 15 (1):e1007507.
Chicago/Turabian StyleSunam Gurung; Nicole Reuter; Alisha Preno; Jamie Dubaut; Hugh Nadeau; Kimberly Hyatt; Krista Singleton; Ashley Martin; W. Tony Parks; James F. Papin; Dean A. Myers. 2019. "Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon." PLOS Pathogens 15, no. 1: e1007507.
Pertussis is a severe respiratory disease caused by Bordetella pertussis . The classic symptoms of pertussis include paroxysmal coughing with an inspiratory whoop, posttussive vomiting, cyanosis, and persistent coryzal symptoms.
Lindsey I. Zimmerman; James F. Papin; Jason Warfel; Roman F. Wolf; Stanley D. Kosanke; Tod J. Merkel. Histopathology of Bordetella pertussis in the Baboon Model. Infection and Immunity 2018, 86, 1 .
AMA StyleLindsey I. Zimmerman, James F. Papin, Jason Warfel, Roman F. Wolf, Stanley D. Kosanke, Tod J. Merkel. Histopathology of Bordetella pertussis in the Baboon Model. Infection and Immunity. 2018; 86 (11):1.
Chicago/Turabian StyleLindsey I. Zimmerman; James F. Papin; Jason Warfel; Roman F. Wolf; Stanley D. Kosanke; Tod J. Merkel. 2018. "Histopathology of Bordetella pertussis in the Baboon Model." Infection and Immunity 86, no. 11: 1.
ZIKV was first identified in 1947 in a sentinel rhesus monkey in Uganda and subsequently spread to Southeast Asia. Until 2007, only a small number of cases were reported, and ZIKV infection was relatively minor until the South Pacific and Brazilian outbreaks, where more severe outcomes were reported. Here, we present the baboon as a nonhuman primate model for contrast and comparison with other published animal models of ZIKV, such as the mouse and macaque species. Baboons breed year round and are not currently a primary nonhuman primate species used in biomedical research, making them more readily available for studies other than human immunodeficiency virus studies, which many macaque species are designated for. This, taken together with the similarities baboons have with humans, such as immunology, reproduction, genetics, and size, makes the baboon an attractive NHP model for ZIKV studies in comparison to other nonhuman primates.
Sunam Gurung; Alisha N. Preno; Jamie P. Dubaut; Hugh Nadeau; Kimberly Hyatt; Nicole Reuter; Bharti Nehete; Roman F. Wolf; Pramod Nehete; Dirk P. Dittmer; Dean A. Myers; James F. Papin. Translational Model of Zika Virus Disease in Baboons. Journal of Virology 2018, 92, 1 .
AMA StyleSunam Gurung, Alisha N. Preno, Jamie P. Dubaut, Hugh Nadeau, Kimberly Hyatt, Nicole Reuter, Bharti Nehete, Roman F. Wolf, Pramod Nehete, Dirk P. Dittmer, Dean A. Myers, James F. Papin. Translational Model of Zika Virus Disease in Baboons. Journal of Virology. 2018; 92 (16):1.
Chicago/Turabian StyleSunam Gurung; Alisha N. Preno; Jamie P. Dubaut; Hugh Nadeau; Kimberly Hyatt; Nicole Reuter; Bharti Nehete; Roman F. Wolf; Pramod Nehete; Dirk P. Dittmer; Dean A. Myers; James F. Papin. 2018. "Translational Model of Zika Virus Disease in Baboons." Journal of Virology 92, no. 16: 1.
Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to a Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and macaques. While microcephaly has been achieved in mice via direct injection of ZIKV into the fetal brain or via interference with interferon signaling, in macaques the primary fetal CZS outcome are ocular defects. In the present study we develope the olive baboon (Papio anubis), as a model for the vertical transfer of ZIKV during pregnancy. We infected four mid-gestation, timed-pregnant baboons with the French Polynesian ZIKV isolate (104ffu) and examined the acute phase of vertical transfer by stopping the study of one dam at 7 days post infection (dpi), two at 14 dpi and one at 21 dpi. All dams exhibited mild to moderate rash and conjunctivitis; three of four dams exhibited viremia at 7 dpi. Of the three dams studied to 14 to 21 days, only one still exhibited viremia on day 14. Vertical transfer of ZIKV to the fetus was found in two pregnancies; in one, vertical transfer was associated with fetal death at ∼14 dpi. In the other, vertical transfer was observed at 21 dpi. Both fetuses had ZIKV RNA in the fetal cerebral cortex as well as other tissues. The 21 dpi fetal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, loss and or damage of immature oligodendrocytes and a loss in neuroprogenitor cells (NPCs). In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL-6 expression. The dams studied to 14 dpi (n=2) and 21 dpi (n=1) exhibited a anti-ZIKV IgM response and IgG response (21 dpi) that included transfer of the IgG to the fetal compartment (cord blood). The severity of systemic inflammatory response (cytokines and chemokines) reflected the vertical transfer of ZIKV in the two pregnancies. As such, these events likely represent the early mechanisms that lead to microcephaly and/or other CNS pathologies in a primate infected with ZIKV and are the first to be described in a non-human primate during the acute phase of ZIKV infection with a contemporaneous ZIKV strain. The baboon thus represents a major NHP for advancing as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs such as macaques.AUTHOR SUMMARYZika virus is endemic in the Americas, primarily spread through mosquitos and sexual contact. Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome (CZS), with the most severe pathology being fetal microcephaly. Developing model organisms that faithfully recreate Zika infection in humans is critical for future development of treatments and preventions. In our present study, we infected Olive baboons at mid-gestation with Zika virus and studied the acute period of viremia and transfer of Zika virus to the fetus during the first three weeks after infection to better understand the timing and mechanisms leading to CZS. We observed Zika virus transfer to fetuses resulting in fetal death in one pregnancy and in a second pregnancy, significant damage to the frontal cortex of the fetal brain consistent with development of microcephaly, closely resembling infection in pregnant women. Our baboon model differs from macaque non-human primate models where the primary fetal outcome during pregnancy following infection with contemporary strains of Zika virus is ocular pathology. Thus, the baboon provides a promising new non-human primate model to further compare and contrast the consequences of Zika virus infection in pregnancy to humans and macaques to better understand the disease.
Sunam Gurung; Nicole Reuter; Alisha Preno; Jamie Dubaut; Hugh Nadeau; Kimberly Hyatt; Krista Singleton; Ashley Martin; W. Tony Parks; James F. Papin; Dean A. Myers. Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. 2018, 331108 .
AMA StyleSunam Gurung, Nicole Reuter, Alisha Preno, Jamie Dubaut, Hugh Nadeau, Kimberly Hyatt, Krista Singleton, Ashley Martin, W. Tony Parks, James F. Papin, Dean A. Myers. Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon. . 2018; ():331108.
Chicago/Turabian StyleSunam Gurung; Nicole Reuter; Alisha Preno; Jamie Dubaut; Hugh Nadeau; Kimberly Hyatt; Krista Singleton; Ashley Martin; W. Tony Parks; James F. Papin; Dean A. Myers. 2018. "Zika virus infection at mid-gestation results in fetal cerebral cortical injury and fetal death in the olive baboon." , no. : 331108.