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The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.
Khalid Alluhaybi; Rahaf Alharbi; Rowa Alhabbab; Najwa Aljehani; Sawsan Alamri; Mohammad Basabrain; Rehaf Alharbi; Wesam Abdulaal; Mohamed Alfaleh; Levi Tamming; Wanyue Zhang; Mazen Hassanain; Abdullah Algaissi; Adel Abuzenadah; Xuguang Li; Anwar Hashem. Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1. Vaccines 2021, 9, 852 .
AMA StyleKhalid Alluhaybi, Rahaf Alharbi, Rowa Alhabbab, Najwa Aljehani, Sawsan Alamri, Mohammad Basabrain, Rehaf Alharbi, Wesam Abdulaal, Mohamed Alfaleh, Levi Tamming, Wanyue Zhang, Mazen Hassanain, Abdullah Algaissi, Adel Abuzenadah, Xuguang Li, Anwar Hashem. Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1. Vaccines. 2021; 9 (8):852.
Chicago/Turabian StyleKhalid Alluhaybi; Rahaf Alharbi; Rowa Alhabbab; Najwa Aljehani; Sawsan Alamri; Mohammad Basabrain; Rehaf Alharbi; Wesam Abdulaal; Mohamed Alfaleh; Levi Tamming; Wanyue Zhang; Mazen Hassanain; Abdullah Algaissi; Adel Abuzenadah; Xuguang Li; Anwar Hashem. 2021. "Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1." Vaccines 9, no. 8: 852.
The Coronavirus Disease 2019 (COVID-19), caused by SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Antigen-specific responses are of unquestionable value for clinical management of COVID-19 patients. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized COVID-19 patients with different disease presentations (i.e., mild, moderate or severe), need for intensive care units (ICU) admission or outcomes (i.e., survival vs death). We show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Interestingly, significantly higher levels of nAbs as well as anti-S1 and -N IgG and IgM antibodies were found in patients with more severe symptoms, patients requiring admission to ICU or those with fatal outcomes. More importantly, early after symptoms onset, we found that the levels of anti-N antibodies correlated strongly with disease severity. Collectively, these findings provide new insights into the kinetics of antibody responses in COVID-19 patients with different disease severity.
Anwar M. Hashem; Abdullah Algaissi; Sarah A. Almahboub; Mohamed A. Alfaleh; Turki S. Abujamel; Sawsan S. Alamri; Khalid A. Alluhaybi; Haya I. Hobani; Rahaf H. AlHarbi; Reem M. Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K. Alharbi; Rowa Y. Alhabbab; Ahdab A. AlSaieedi; Wesam H. Abdulaal; Abdullah Bukhari; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Arnab Pain; Almohanad A. Alkayyal; Naif A. M. Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. Viruses 2020, 12, 1390 .
AMA StyleAnwar M. Hashem, Abdullah Algaissi, Sarah A. Almahboub, Mohamed A. Alfaleh, Turki S. Abujamel, Sawsan S. Alamri, Khalid A. Alluhaybi, Haya I. Hobani, Rahaf H. AlHarbi, Reem M. Alsulaiman, M-Zaki ElAssouli, Sharif Hala, Naif K. Alharbi, Rowa Y. Alhabbab, Ahdab A. AlSaieedi, Wesam H. Abdulaal, Abdullah Bukhari, Afrah A. Al-Somali, Fadwa S. Alofi, Asim A. Khogeer, Arnab Pain, Almohanad A. Alkayyal, Naif A. M. Almontashiri, Ahmad Bakur Mahmoud, Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. Viruses. 2020; 12 (12):1390.
Chicago/Turabian StyleAnwar M. Hashem; Abdullah Algaissi; Sarah A. Almahboub; Mohamed A. Alfaleh; Turki S. Abujamel; Sawsan S. Alamri; Khalid A. Alluhaybi; Haya I. Hobani; Rahaf H. AlHarbi; Reem M. Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K. Alharbi; Rowa Y. Alhabbab; Ahdab A. AlSaieedi; Wesam H. Abdulaal; Abdullah Bukhari; Afrah A. Al-Somali; Fadwa S. Alofi; Asim A. Khogeer; Arnab Pain; Almohanad A. Alkayyal; Naif A. M. Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. 2020. "Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients." Viruses 12, no. 12: 1390.
The Coronavirus Disease 2019 (COVID-19), caused by the novel SARS-CoV-2, continues to spread globally with significantly high morbidity and mortality rates. Immunological surrogate markers, in particular antigen-specific responses, are of unquestionable value for clinical management of patients with COVID-19. Here, we investigated the kinetics of IgM, IgG against the spike (S) and nucleoproteins (N) proteins and their neutralizing capabilities in hospitalized patients with RT-PCR confirmed COVID-19 infection. Our data show that SARS-CoV-2 specific IgG, IgM and neutralizing antibodies (nAbs) were readily detectable in almost all COVID-19 patients with various clinical presentations. Notably, anti-S and -N IgG, peaked 20-40 day after disease onset, and were still detectable for at least up to 70 days, with nAbs observed during the same time period. Moreover, nAbs titers were strongly correlated with IgG antibodies. Significantly higher levels of nAbs as well as anti-S1 and N IgG and IgM antibodies were found in patients with more severe clinical presentations, patients requiring admission to intensive care units (ICU) or those with fatal outcomes. Interestingly, lower levels of antibodies, particularly anti-N IgG and IgM in the first 15 days after symptoms onset, were found in survivors and those with mild clinical presentations. Collectively, these findings provide new insights into the characteristics and kinetics of antibody responses in COVID-19 patients with different disease severity.
Anwar M Hashem; Abdullah Algaissi; Sarah A Almahboub; Mohamed A Alfaleh; Turki S Abujamel; Sawsan S Alamri; Khalid A Alluhaybi; Haya I Hobani; Rahaf H AlHarbi; Reem M Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K Alharbi; Rowa Y Alhabbab; Ahdab A AlSaieedi; Wesam H Abdulaal; Abdullah Bukhari; Afrah A Al-Somali; Fadwa S Alofi; Asim A Khogeer; Arnab Pain; Almohanad A Alkayyal; Naif Am Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. 2020, 1 .
AMA StyleAnwar M Hashem, Abdullah Algaissi, Sarah A Almahboub, Mohamed A Alfaleh, Turki S Abujamel, Sawsan S Alamri, Khalid A Alluhaybi, Haya I Hobani, Rahaf H AlHarbi, Reem M Alsulaiman, M-Zaki ElAssouli, Sharif Hala, Naif K Alharbi, Rowa Y Alhabbab, Ahdab A AlSaieedi, Wesam H Abdulaal, Abdullah Bukhari, Afrah A Al-Somali, Fadwa S Alofi, Asim A Khogeer, Arnab Pain, Almohanad A Alkayyal, Naif Am Almontashiri, Ahmad Bakur Mahmoud, Xuguang Li. Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients. . 2020; ():1.
Chicago/Turabian StyleAnwar M Hashem; Abdullah Algaissi; Sarah A Almahboub; Mohamed A Alfaleh; Turki S Abujamel; Sawsan S Alamri; Khalid A Alluhaybi; Haya I Hobani; Rahaf H AlHarbi; Reem M Alsulaiman; M-Zaki ElAssouli; Sharif Hala; Naif K Alharbi; Rowa Y Alhabbab; Ahdab A AlSaieedi; Wesam H Abdulaal; Abdullah Bukhari; Afrah A Al-Somali; Fadwa S Alofi; Asim A Khogeer; Arnab Pain; Almohanad A Alkayyal; Naif Am Almontashiri; Ahmad Bakur Mahmoud; Xuguang Li. 2020. "Early Humoral Response Correlates with Disease Severity and Outcomes in COVID-19 Patients." , no. : 1.
Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that, in turn, promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report we analyzed clinical datasets of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We, thus, developed a new therapeutic approach to inhibit EGFR and hypoxia by combination treatment with metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24− and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic; this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.
Andrew Sulaiman; Sarah McGarry; Jason Chambers; Emil Al-Kadi; Alexandra Phan; Li Li; Karan Mediratta; Jim Dimitroulakos; Christina Addison; Xuguang Li; Lisheng Wang. Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells. International Journal of Molecular Sciences 2020, 21, 5788 .
AMA StyleAndrew Sulaiman, Sarah McGarry, Jason Chambers, Emil Al-Kadi, Alexandra Phan, Li Li, Karan Mediratta, Jim Dimitroulakos, Christina Addison, Xuguang Li, Lisheng Wang. Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells. International Journal of Molecular Sciences. 2020; 21 (16):5788.
Chicago/Turabian StyleAndrew Sulaiman; Sarah McGarry; Jason Chambers; Emil Al-Kadi; Alexandra Phan; Li Li; Karan Mediratta; Jim Dimitroulakos; Christina Addison; Xuguang Li; Lisheng Wang. 2020. "Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells." International Journal of Molecular Sciences 21, no. 16: 5788.
Development of targeted therapies for triple-negative breast cancer (TNBC) is an unmet medical need. Cisplatin has demonstrated its promising potential for the treatment of TNBC in clinical trials; however, cisplatin treatment is associated with hypoxia that in turn promotes cancer stem cell (CSC) enrichment and drug resistance. Therapeutic approaches to attenuate this may lead to increased cisplatin efficacy in the clinic for the treatment of TNBC. In this report, we analyzed clinical dataset of TNBC and found that TNBC patients possessed higher levels of EGFR and hypoxia gene expression. A similar expression pattern was also observed in cisplatin-resistant ovarian cancer cells. We thus developed a new therapeutic approach to inhibit EGFR and hypoxia by combination of metformin and gefitinib that sensitized TNBC cells to cisplatin and led to the inhibition of both CD44+/CD24- and ALDH+ CSCs. We demonstrated a similar inhibition efficacy on organotypic cultures of TNBC patient samples ex vivo. Since these drugs have already been used frequently in the clinic, this study illustrates a novel, clinically translatable therapeutic approach to treat patients with TNBC.
Andrew Sulaiman; Sarah McGarry; Jason Chambers; Emil Al-Kadi; Alexandra Phan; Li Li; Karan Mediratta; Jim Dimitroulakos; Christina Addison; Xuguang Li; Lisheng Wang. Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells. 2020, 1 .
AMA StyleAndrew Sulaiman, Sarah McGarry, Jason Chambers, Emil Al-Kadi, Alexandra Phan, Li Li, Karan Mediratta, Jim Dimitroulakos, Christina Addison, Xuguang Li, Lisheng Wang. Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells. . 2020; ():1.
Chicago/Turabian StyleAndrew Sulaiman; Sarah McGarry; Jason Chambers; Emil Al-Kadi; Alexandra Phan; Li Li; Karan Mediratta; Jim Dimitroulakos; Christina Addison; Xuguang Li; Lisheng Wang. 2020. "Targeting Hypoxia Sensitizes TNBC to Cisplatin and Promotes Inhibition of Both Bulk and Cancer Stem Cells." , no. : 1.
Zika virus (ZIKV) infection is a serious public threat with cases reported in about 70 countries and territories. One of the most serious consequences of ZIKV infection is congenital microcephaly in babies. Congenital microcephaly has been suggested to result from infection of neural progenitor cells (NPCs) in the developing fetal brain. However, the molecular and cellular mechanisms underlying microcephaly development remains to be fully elucidated. In this study, we employed quantitative proteomics to determine protein expression profile that occur during viral replication in NPCs. Bioinformatics analysis of the protein expression changes resulted in the identification of a wide range of cell signaling pathways. Specifically, pathways involved in neurogenesis and embryonic development were markedly altered, along with those associated with cell cycle, apoptosis, lipid metabolism and oxidative stress. Notably, the differential regulation of Ephrin Receptor and PPAR signaling pathways, as revealed by quantitative proteomics and validated by qPCR array, underscores the need to explore these pathways in disease development. Collectively, these results indicate that ZIKV-induced pathogenesis involves complex virus-host reactions; the findings reported here could help shed light on the mechanisms underlying ZIKV-induced microcephaly and ZIKV replication in NPCs.
Sathya N. Thulasi Raman; Elyse Latreille; Jun Gao; Wanyue Zhang; Jianguo Wu; Marsha S. Russell; Lisa Walrond; Terry Cyr; Jessie R. Lavoie; David Safronetz; Jingxin Cao; Simon Sauve; Aaron Farnsworth; Wangxue Chen; Pei-Yong Shi; Youchun Wang; Lisheng Wang; Michael Rosu-Myles; Xuguang Li. Dysregulation of Ephrin Receptor and PPAR signaling pathways in Neural Progenitor Cells Infected by Zika Virus. Emerging Microbes & Infections 2020, 9, 1 -50.
AMA StyleSathya N. Thulasi Raman, Elyse Latreille, Jun Gao, Wanyue Zhang, Jianguo Wu, Marsha S. Russell, Lisa Walrond, Terry Cyr, Jessie R. Lavoie, David Safronetz, Jingxin Cao, Simon Sauve, Aaron Farnsworth, Wangxue Chen, Pei-Yong Shi, Youchun Wang, Lisheng Wang, Michael Rosu-Myles, Xuguang Li. Dysregulation of Ephrin Receptor and PPAR signaling pathways in Neural Progenitor Cells Infected by Zika Virus. Emerging Microbes & Infections. 2020; 9 (1):1-50.
Chicago/Turabian StyleSathya N. Thulasi Raman; Elyse Latreille; Jun Gao; Wanyue Zhang; Jianguo Wu; Marsha S. Russell; Lisa Walrond; Terry Cyr; Jessie R. Lavoie; David Safronetz; Jingxin Cao; Simon Sauve; Aaron Farnsworth; Wangxue Chen; Pei-Yong Shi; Youchun Wang; Lisheng Wang; Michael Rosu-Myles; Xuguang Li. 2020. "Dysregulation of Ephrin Receptor and PPAR signaling pathways in Neural Progenitor Cells Infected by Zika Virus." Emerging Microbes & Infections 9, no. 1: 1-50.
Vaccine induced responses are often weaker in those individuals most susceptible to infection, namely the very young and the elderly, highlighting the need for safe and effective vaccine adjuvants. Herein we evaluated different archaeosome formulations as an adjuvant to the H1N1 influenza hemagglutinin protein and compared immune responses (anti-HA IgG and hemagglutination inhibition assay titers) as well as protection to an influenza A virus (strainA/PuertoRico/8/1934H1N1)homologous challenge to those generated using a squalene-based oil-in-water nano-emulsion, AddaVax™ in a murine model. The impact of age (young adult vs aged) on vaccine induced immune responses as well as the protection in pups due to the transfer of maternal antibodies was measured. Overall, we show that archaeal lipid based adjuvants can induce potent anti-HA responses in young and aged mice that can also be passed from vaccinated mothers to pups. Furthermore, young and aged mice immunized with archaeal lipid adjuvants as well as pups from immunized mothers were protected from challenge with influenza. In addition, we show that a simple admixed archaeosome formulation composed of a single sulfated glycolipid namely sulfated lactosylarchaeol (SLA; 6'-sulfate-β-D-Galp-(1,4)-β-D-Glcp-(1,1)-archaeol) can give equal or better protection compared to AddaVax™ or the traditional antigen-encapsulated archaeosome formulations.
Felicity C. Stark; Bassel Akache; Amalia Ponce; Renu Dudani; Lise Deschatelets; Yimei Jia; Janelle Sauvageau; Dean Williams; Mohammad P. Jamshidi; Gerard Agbayani; Kristina Wachholz; Blair A. Harrison; Xuguang Li; Lakshmi Krishnan; Wangxue Chen; Michael J. McCluskie. Archaeal glycolipid adjuvanted vaccines induce strong influenza-specific immune responses through direct immunization in young and aged mice or through passive maternal immunization. Vaccine 2019, 37, 7108 -7116.
AMA StyleFelicity C. Stark, Bassel Akache, Amalia Ponce, Renu Dudani, Lise Deschatelets, Yimei Jia, Janelle Sauvageau, Dean Williams, Mohammad P. Jamshidi, Gerard Agbayani, Kristina Wachholz, Blair A. Harrison, Xuguang Li, Lakshmi Krishnan, Wangxue Chen, Michael J. McCluskie. Archaeal glycolipid adjuvanted vaccines induce strong influenza-specific immune responses through direct immunization in young and aged mice or through passive maternal immunization. Vaccine. 2019; 37 (47):7108-7116.
Chicago/Turabian StyleFelicity C. Stark; Bassel Akache; Amalia Ponce; Renu Dudani; Lise Deschatelets; Yimei Jia; Janelle Sauvageau; Dean Williams; Mohammad P. Jamshidi; Gerard Agbayani; Kristina Wachholz; Blair A. Harrison; Xuguang Li; Lakshmi Krishnan; Wangxue Chen; Michael J. McCluskie. 2019. "Archaeal glycolipid adjuvanted vaccines induce strong influenza-specific immune responses through direct immunization in young and aged mice or through passive maternal immunization." Vaccine 37, no. 47: 7108-7116.
Sigmodon hispidus or cotton rat is an excellent animal model for studying human infections of respiratory viruses including respiratory syncytial virus (RSV), which is the leading cause of hospitalization in infants and causes high rates of infection in the elderly and immunocompromised patient populations. Despite several decades of research, no vaccine has been licensed whereas inactivated vaccines have been shown to induce severe adverse reaction in a clinical trial, with other forms of RSV vaccine also found to induce enhanced disease in preclinical animal studies. While arguably the cotton rat is the best small animal model for evaluation of RSV vaccines and antivirals, many important genes of the immune system remain to be isolated. Programmed cell death-1 (PD-1) plays an integral role in regulating many aspects of immunity by inducing suppressive signals. In this study, we report the isolation of mRNA encoding the cotton rat PD-1 (crPD-1) and characterization of the PD-1 protein. crPD-1 bound to its cognate ligand on dendritic cells and effectively suppressed cytokine secretion. Moreover, using the newly acquired gene sequence, we observed a decreased level of crPD-1 levels in cotton rats with enhanced respiratory disease induced by inactivated RSV vaccine, unraveling a new facet of vaccine-induced disease.
Abenaya Muralidharan; Louise Larocque; Marsha Russell; Marybeth Creskey; Changgui Li; Wangxue Chen; Gary Van Domselaar; Jingxin Cao; Terry Cyr; Michael Rosu-Myles; Lisheng Wang; Xuguang Li. PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease. Scientific Reports 2019, 9, 1 -12.
AMA StyleAbenaya Muralidharan, Louise Larocque, Marsha Russell, Marybeth Creskey, Changgui Li, Wangxue Chen, Gary Van Domselaar, Jingxin Cao, Terry Cyr, Michael Rosu-Myles, Lisheng Wang, Xuguang Li. PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease. Scientific Reports. 2019; 9 (1):1-12.
Chicago/Turabian StyleAbenaya Muralidharan; Louise Larocque; Marsha Russell; Marybeth Creskey; Changgui Li; Wangxue Chen; Gary Van Domselaar; Jingxin Cao; Terry Cyr; Michael Rosu-Myles; Lisheng Wang; Xuguang Li. 2019. "PD-1 of Sigmodon hispidus: Gene identification, characterization and preliminary evaluation of expression in inactivated RSV vaccine-induced enhanced respiratory disease." Scientific Reports 9, no. 1: 1-12.
Neuraminidase is the second major surface antigen on influenza virus. We investigated the immunogenicity and cross protective efficacy of virus-like particle containing neuraminidase derived from 2009 pandemic H1N1 influenza virus (N1 VLP) in comparison with inactivated split influenza vaccine. Immunization of mice with N1 VLP induced antibody responses specific for virus and cross-reactive neuraminidase inhibition activity whereas an inactivated split vaccine induced strain-specific hemagglutination inhibition activity. N1 VLP-immunized mice developed cross protective immunity against antigenically different influenza viruses, as determined by body weight changes, lung viral titers, infiltrating innate immune cells, and cytokines, and antibody secreting cells, and germinal center B cells. Also, N1 VLP-immune sera provided cross-protection in naïve mice. Immunity by N1 VLP vaccination was not compromised in Fc receptor γ-chain deficient mice. These results suggest that neuraminidase-presenting VLP can be developed as an effective cross-protective vaccine candidate along with current influenza vaccination.
Ki-Hye Kim; Young-Tae Lee; Soojin Park; Yu-Jin Jung; Youri Lee; Eun-Ju Ko; Yu-Jin Kim; Xuguang Li; Sang-Moo Kang. Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus. Virology 2019, 535, 179 -188.
AMA StyleKi-Hye Kim, Young-Tae Lee, Soojin Park, Yu-Jin Jung, Youri Lee, Eun-Ju Ko, Yu-Jin Kim, Xuguang Li, Sang-Moo Kang. Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus. Virology. 2019; 535 ():179-188.
Chicago/Turabian StyleKi-Hye Kim; Young-Tae Lee; Soojin Park; Yu-Jin Jung; Youri Lee; Eun-Ju Ko; Yu-Jin Kim; Xuguang Li; Sang-Moo Kang. 2019. "Neuraminidase expressing virus-like particle vaccine provides effective cross protection against influenza virus." Virology 535, no. : 179-188.
The high global burden of tuberculosis (TB) underscores the urgent need for an effective TB vaccine since the only licensed Bacillus Calmette-Guérin (BCG) vaccine is ineffective in preventing adult pulmonary TB and affords no protection against latent TB infection (LTBI). Herein we investigated the potential of Mycobacterium tuberculosis (Mtb) antigen proteins AEC comprised of Ag85b and ESAT6-CFP10 proteins in conjunction with aluminum (Al) and polyriboinosinic-polyribocytidylic acid (poly-IC) as a novel subunit vaccine against TB. The immunogenicity and protection induced by the adjuvanted vaccine were evaluated in two animal models. Mice vaccinated with AEC/Al/poly-IC exhibited significant antigen-specific humoral immune responses and cell-mediated immunity as determined by immunoassay and multicolor flow cytometric assay, and the protective effect of the vaccine was demonstrated in a guinea pig model of latent Mtb infection. Compared to the control group, the mean pathological scores and bacterial loads in lungs and spleens of AEC/Al/poly-IC-immunized guinea pigs were significantly reduced. These data indicate that the AEC/Al/poly-IC is highly immunogenic in mice and can effectively protect guinea pigs against latent Mtb infection; it may represent a promising candidate vaccine for the control of latent TB.
Chunhua Wang; Jinbiao Lu; Weixin Du; Guozhi Wang; Xuguang Li; Xiaobin Shen; Cheng Su; Lei Yang; Baowen Chen; Junzhi Wang; Miao Xu. Ag85b/ESAT6-CFP10 adjuvanted with aluminum/poly-IC effectively protects guinea pigs from latent mycobacterium tuberculosis infection. Vaccine 2019, 37, 4477 -4484.
AMA StyleChunhua Wang, Jinbiao Lu, Weixin Du, Guozhi Wang, Xuguang Li, Xiaobin Shen, Cheng Su, Lei Yang, Baowen Chen, Junzhi Wang, Miao Xu. Ag85b/ESAT6-CFP10 adjuvanted with aluminum/poly-IC effectively protects guinea pigs from latent mycobacterium tuberculosis infection. Vaccine. 2019; 37 (32):4477-4484.
Chicago/Turabian StyleChunhua Wang; Jinbiao Lu; Weixin Du; Guozhi Wang; Xuguang Li; Xiaobin Shen; Cheng Su; Lei Yang; Baowen Chen; Junzhi Wang; Miao Xu. 2019. "Ag85b/ESAT6-CFP10 adjuvanted with aluminum/poly-IC effectively protects guinea pigs from latent mycobacterium tuberculosis infection." Vaccine 37, no. 32: 4477-4484.
Chitosan is a polysaccharide capable of augmenting immune responses with a proven safety record in animals and humans. These properties make it a potentially attractive agent for the prevention and treatment of infectious disease. Infection by respiratory syncytial virus (RSV) is the leading cause of serious lower respiratory disease in young children throughout the world. There is no licensed vaccine available against RSV whereas inactivated vaccine is known to cause enhanced respiratory disease instead of protection. Here, we investigated whether chitosan administered one or three days post-infection could protect animals against RSV infection and whether it could alter immune responses or immunopathology induced by inactivated RSV vaccine when administered twice before RSV infection. We found chitosan could modestly protect animals against RSV infection when given post-infection, while, in conjunction with inactivated RSV vaccine when given pre-infection, it could significantly reduce RSV infection in mice. Further mechanistic investigation revealed that chitosan enhanced antigen-specific immune responses through augmenting the induction of regulatory T cells, lung resident T cells and neutralizing antibodies while reversing Th2-skewed immune responses induced by inactivated RSV vaccine but, surprisingly, failing to reverse lung histopathology. Overall, this study sheds more light on the molecular mechanisms underlying inactivated RSV vaccine-induced disease.
Abenaya Muralidharan; Marsha S. Russell; Louise Larocque; Caroline Gravel; Simon Sauvé; Ze Chen; Changgui Li; Wangxue Chen; Terry Cyr; Michael Rosu-Myles; Lisheng Wang; Xuguang Li. Chitosan alters inactivated respiratory syncytial virus vaccine elicited immune responses without affecting lung histopathology in mice. Vaccine 2019, 37, 4031 -4039.
AMA StyleAbenaya Muralidharan, Marsha S. Russell, Louise Larocque, Caroline Gravel, Simon Sauvé, Ze Chen, Changgui Li, Wangxue Chen, Terry Cyr, Michael Rosu-Myles, Lisheng Wang, Xuguang Li. Chitosan alters inactivated respiratory syncytial virus vaccine elicited immune responses without affecting lung histopathology in mice. Vaccine. 2019; 37 (30):4031-4039.
Chicago/Turabian StyleAbenaya Muralidharan; Marsha S. Russell; Louise Larocque; Caroline Gravel; Simon Sauvé; Ze Chen; Changgui Li; Wangxue Chen; Terry Cyr; Michael Rosu-Myles; Lisheng Wang; Xuguang Li. 2019. "Chitosan alters inactivated respiratory syncytial virus vaccine elicited immune responses without affecting lung histopathology in mice." Vaccine 37, no. 30: 4031-4039.
Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses. The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein. The recombinant cotton rat CD40L protein was recognized by an antibody against mouse CD40L. Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression. The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.
Marsha S. Russell; Abenaya Muralidharan; Louise Larocque; Jingxin Cao; Yvon Deschambault; Jessie Varga; Sathya N. Thulasi Raman; Xuguang Li. Identification and characterisation of the CD40-ligand of Sigmodon hispidus. PLOS ONE 2018, 13, e0199067 .
AMA StyleMarsha S. Russell, Abenaya Muralidharan, Louise Larocque, Jingxin Cao, Yvon Deschambault, Jessie Varga, Sathya N. Thulasi Raman, Xuguang Li. Identification and characterisation of the CD40-ligand of Sigmodon hispidus. PLOS ONE. 2018; 13 (7):e0199067.
Chicago/Turabian StyleMarsha S. Russell; Abenaya Muralidharan; Louise Larocque; Jingxin Cao; Yvon Deschambault; Jessie Varga; Sathya N. Thulasi Raman; Xuguang Li. 2018. "Identification and characterisation of the CD40-ligand of Sigmodon hispidus." PLOS ONE 13, no. 7: e0199067.
Cotton rats are an important animal model to study infectious diseases. They have demonstrated higher susceptibility to a wider variety of human pathogens than other rodents and are also the animal model of choice for pre-clinical evaluations of some vaccine candidates. However, the genome of cotton rats remains to be fully sequenced, with much fewer genes cloned and characterised compared to other rodent species. Here we report the cloning and characterization of CD40 ligand, whose human and murine counterparts are known to be expressed on a range of cell types including activated T cells and B cells, dendritic cells, granulocytes, macrophages and platelets and exerts a broad array of immune responses. The cDNA for cotton rat CD40L we isolated is comprised of 1104 nucleotides with an open reading frame (ORF) of 783bp coding for a 260 amino acid protein. The recombinant cotton rat CD40L protein was recognized by an antibody against mouse CD40L. Moreover, it demonstrated functional activities on immature bone marrow dendritic cells by upregulating surface maturation markers (CD40, CD54, CD80, and CD86), and increasing IL-6 gene and protein expression. The availability of CD40L gene identity could greatly facilitate mechanistic research on pathogen-induced-immunopathogenesis and vaccine-elicited immune responses.
Marsha S. Russell; Abenaya Muralidharan; Louise Larocque; Jingxin Cao; Yvon Deschambault; Jessie Varga; Sathya N. Thulasi Raman; Xuguang Li. Identification and Characterisation of the CD40-Ligand ofSigmodon hispidus. 2018, 337089 .
AMA StyleMarsha S. Russell, Abenaya Muralidharan, Louise Larocque, Jingxin Cao, Yvon Deschambault, Jessie Varga, Sathya N. Thulasi Raman, Xuguang Li. Identification and Characterisation of the CD40-Ligand ofSigmodon hispidus. . 2018; ():337089.
Chicago/Turabian StyleMarsha S. Russell; Abenaya Muralidharan; Louise Larocque; Jingxin Cao; Yvon Deschambault; Jessie Varga; Sathya N. Thulasi Raman; Xuguang Li. 2018. "Identification and Characterisation of the CD40-Ligand ofSigmodon hispidus." , no. : 337089.
The only universally conserved sequence amongst all influenza A viral neuraminidase (NA) is located between amino acids 222-230 and plays crucial roles in viral replication. However, it remained unclear as to whether this universal epitope is exposed during the course of infection to allow binding and inhibition by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope, we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb. Moreover, the antibody also provided heterosubtypic protection in mice challenged with lethal doses of mouse-adapted H1N1 and H3N2, which represent group I and II viruses, respectively. Furthermore, we report amino acid residues I222 and E227, located in close proximity to the active site, are indispensable for inhibition by this antibody. This unique, highly-conserved linear sequence in viral NA could be an attractive immunological target for protection against diverse strains of influenza viruses.
Tracey M. Doyle; Anwar M. Hashem; Changgui Li; Gary Van Domselaar; Louise Larocque; Junzhi Wang; Daryl Smith; Terry Cyr; Aaron Farnsworth; Runtao He; Aeron C. Hurt; Earl G. Brown; Xuguang Li. Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antiviral Research 2013, 100, 567 -574.
AMA StyleTracey M. Doyle, Anwar M. Hashem, Changgui Li, Gary Van Domselaar, Louise Larocque, Junzhi Wang, Daryl Smith, Terry Cyr, Aaron Farnsworth, Runtao He, Aeron C. Hurt, Earl G. Brown, Xuguang Li. Universal anti-neuraminidase antibody inhibiting all influenza A subtypes. Antiviral Research. 2013; 100 (2):567-574.
Chicago/Turabian StyleTracey M. Doyle; Anwar M. Hashem; Changgui Li; Gary Van Domselaar; Louise Larocque; Junzhi Wang; Daryl Smith; Terry Cyr; Aaron Farnsworth; Runtao He; Aeron C. Hurt; Earl G. Brown; Xuguang Li. 2013. "Universal anti-neuraminidase antibody inhibiting all influenza A subtypes." Antiviral Research 100, no. 2: 567-574.
All influenza viral neuraminidases (NA) of both type A and B viruses have only one universally conserved sequence located between amino acids 222-230. A monoclonal antibody against this region has been previously reported to provide broad inhibition against all nine subtypes of influenza A NA; yet its inhibitory effect against influenza B viral NA remained unknown. Here, we report that the monoclonal antibody provides a broad inhibition against various strains of influenza B viruses of both Victoria and Yamagata genetic lineage. Moreover, the growth and NA enzymatic activity of two drug resistant influenza B strains (E117D and D197E) are also inhibited by the antibody even though these two mutations are conformationally proximal to the universal epitope. Collectively, these data suggest that this unique, highly-conserved linear sequence in viral NA is exposed sufficiently to allow access by inhibitory antibody during the course of infection; it could represent a potential target for antiviral agents and vaccine-induced immune responses against diverse strains of type B influenza virus.
Tracey M. Doyle; Changgui Li; Doris J. Bucher; Anwar M. Hashem; Gary Van Domselaar; Junzhi Wang; Aaron Farnsworth; Yi-Min She; Terry Cyr; Runtao He; Earl G. Brown; Aeron C. Hurt; Xuguang Li. A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains. Biochemical and Biophysical Research Communications 2013, 441, 226 -229.
AMA StyleTracey M. Doyle, Changgui Li, Doris J. Bucher, Anwar M. Hashem, Gary Van Domselaar, Junzhi Wang, Aaron Farnsworth, Yi-Min She, Terry Cyr, Runtao He, Earl G. Brown, Aeron C. Hurt, Xuguang Li. A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains. Biochemical and Biophysical Research Communications. 2013; 441 (1):226-229.
Chicago/Turabian StyleTracey M. Doyle; Changgui Li; Doris J. Bucher; Anwar M. Hashem; Gary Van Domselaar; Junzhi Wang; Aaron Farnsworth; Yi-Min She; Terry Cyr; Runtao He; Earl G. Brown; Aeron C. Hurt; Xuguang Li. 2013. "A monoclonal antibody targeting a highly conserved epitope in influenza B neuraminidase provides protection against drug resistant strains." Biochemical and Biophysical Research Communications 441, no. 1: 226-229.