I3V Research impact

Infectious diseases remain major causes of preventable mortality and morbidity worldwide. New vaccines and mechanisms to ensure their appropriate and cost-effective use are required to meet these challenges. Chronic inflammatory diseases are a particular burden in aging populations. Rheumatoid arthritis, multiple sclerosis and Inflammatory Bowel Diseases are particularly prevalent in the Maritime Provinces for reasons which are poorly understood. New immune-based therapies for cancer are already having some impact, even in metastatic disease, and highlight the tremendous opportunities for harnessing manipulation of immune responses and viroceutical therapies to combat such disease. With Nova Scotia having the highest per capita cancer incidence in the country, with increased global concern for viral pandemics and emerging viral diseases, and with an interest in expanding research activity in the regional biotechnology sector, our objectives clearly align with Nova Scotia’s research and economic development priorities as described in the 2014 One Nova Scotia report.

The impact of I3V research can be measured in a variety of ways both locally and globally, which includes:

• New licenced treatments

• Clinical trials

• Patents and intellectual property

• Peer-reviewed publications and citations

• Training of the next generation of researchers and clinicians

• Informing and engaging community and stakeholders

2020

Ahmed MA, Naus M, Singer J, Valiquette L, Coleman BL, De Serres G, Vanderkooi OG, Top KA, Isenor JE, Kellner JD, McCarthy AE, Bettinger JA; Canadian Immunization Research Network (CIRN). (2020) Investigating the association of receipt of seasonal influenza vaccine with occurrence of anesthesia/paresthesia and severe headaches, Canada 2012/13-2016/17, the Canadian Vaccine Safety Network. Vaccine. Apr 23;38(19):3582-3590. doi: 10.1016/j.vaccine.2020.03.018.

Bermejo-Martin JF, Almansa R, Torres A, González-Rivera M, Kelvin DJ. (2020) COVID-19 as a cardiovascular disease: the potential role of chronic endothelial dysfunction. Cardiovascular Research May 18:cvaa140. doi: 10.1093/cvr/cvaa140.

Daboor SM, Rohde JR, Cheng Z (2020) Disruption of the extracellular polymeric network of Pseudomonas aeruginosa biofilms by alginate lyase enhances pathogen eradication by antibiotics. Journal of Cystic Fibrosis. May 30:S1569-1993(20)30119-3. doi: 10.1016/j.jcf.2020.04.006.

Daly R, Khaperskyy DA, Gaglia MM. (2020) Fine-tuning a blunt tool: Regulation of viral host shutoff RNases. PLoS Pathogens Apr 8;16(4):e1008385. doi: 10.1371/journal.ppat.1008385.

Davis IRC, McNeil SA, Allen W, MacKinnon-Cameron D, Lindsay LR, Bernat K, Dibernardo A, LeBlanc JJ, Hatchette TF. (2020) Performance of a Modified Two-Tiered Testing (MTTT) EIA Algorithm for Serologic Diagnosis of Lyme Disease in Nova Scotia. Journal of Clinical Microbiology Apr 22:JCM.01841-19. doi: 10.1128/JCM.01841-19.

Dawod B, Haidl ID, Azad MB, Marshall JS. (2020) Toll-like receptor 2 impacts the development of oral tolerance in mouse pups via a milk-dependent mechanism. Journal of Allergy and Clinical Immunology Feb 15:S0091-6749(20)30192-5. doi: 10.1016/j.jaci.2020.01.049.

Douglas GM, Bielawski JP, Langille MGI. (2020) Re-evaluating the relationship between missing heritability and the microbiome. Microbiome Jun 8;8(1):87. doi: 10.1186/s40168-020-00839-4.

Douglas GM, Maffei VJ, Zaneveld JR, Yurgel SN, Brown JR, Taylor CM, Huttenhower C, Langille MGI. (2020) PICRUSt2 for prediction of metagenome functions. Nature Biotechnology Jun;38(6):685-688. doi: 10.1038/s41587-020-0548-6.

Fokam D, Dickson K, Kamali K, Holbein B, Colp P, Stueck A, Zhou J, Lehmann C (2020) Iron Chelation in Murine Models of Systemic Inflammation Induced by Gram-Positive and Gram-Negative Toxins. Antibiotics May 26;9(6):E283. doi: 10.3390/antibiotics9060283.

Giacomantonio MA, Sterea AM, Kim Y, Paulo JA, Clements DR, Kennedy BE, Bydoun MJ, Shi G, Waisman DM, Gygi SP, Giacomantonio CA, Murphy JP, Gujar S (2020) Quantitative Proteome Responses to Oncolytic Reovirus in GM-CSF- and M-CSF-Differentiated Bone Marrow-Derived Cells. Journal of Proteome Research 19(2):708-718.

Hanly JG, Urowitz MB, Gordon C, Bae SC, Romero-Diaz J, Sanchez-Guerrero J, Bernatsky S, Clarke AE, Wallace DJ, Isenberg DA, Rahman A, Merrill JT, Fortin PR, Gladman DD, Bruce IN, Petri M, Ginzler EM, Dooley MA, Ramsey-Goldman R, Manzi S, Jönsen A, Alarcón GS, van Vollenhoven RF, Aranow C, Mackay M, Ruiz-Irastorza G, Lim S, Inanc M, Kalunian KC, Jacobsen S, Peschken CA, Kamen DL, Askanase A, Farewell V. (2020) Neuropsychiatric events in systemic lupus erythematosus: a longitudinal analysis of outcomes in an international inception cohort using a multistate model approach. Ann Rheum Dis Mar;79(3):356-362. doi: 10.1136/annrheumdis-2019-216150.

Hargreaves BKV, Roberts SE, Derfalvi B, Boudreau JE (2020) Highly efficient serum-free manipulation of miRNA in human NK cells without loss of viability or phenotypic alterations is accomplished with TransIT-TKO. PLoS ONE Apr 17;15(4):e0231664. doi: 10.1371/journal.pone.0231664.

Herder M, Morten CJ, Doshi P. (2020) Integrated Drug Reviews at the US Food and Drug Administration-Legal Concerns and Knowledge Lost. JAMA Inter Med Mar 2. doi: 10.1001/jamainternmed.2020.0074.

Isenor JE, Helwig M, Weale MB, Bowles SK. (2020) Evaluation of the experiences and needs of users of a drug information resources website. J. Med. Libr. Assoc. Apr;108(2):270-277. doi: 10.5195/jmla.2020.446.

Isenor JE, Kervin MS, Halperin DM, Langley J, Bettinger JA, Top KA, Lalji F, Slayter K, Kaczorowski J, Bowles SK, Waite NM, Halperin SA. (2020) Pharmacists as immunizers to Improve coverage and provider/recipient satisfaction: A prospective, Controlled Community Embedded Study with vaccineS with low coverage rates (the Improve ACCESS Study): Study summary and anticipated significance. Can Pharm J (Ott). Feb 17;153(2):88-94. doi: 10.1177/1715163519900221. eCollection 2020 Mar-Apr.

Kelvin AA, Halperin S (2020) COVID-19 in children: the link in the transmission chain. Lancet Infectious Disease Jun;20(6):633-634. doi: 10.1016/S1473-3099(20)30236-X.

Kelvin DJ, Rubino S. (2020) Fear of the novel coronavirus. Journal of Infection in Developing Countries Jan 31;14(1):1-2. doi: 10.3855/jidc.12496.

Kennedy BE, Sadek M, Gujar SA (2020) Targeted Metabolic Reprogramming to Improve the Efficacy of Oncolytic Virus Therapy. Molecular Therapy 28(6):1417-1421.

Kennedy BE, Sadek M, Elnenaei MO, Reiman A, Gujar SA (2020) Targeting NAD+ Synthesis to Potentiate CD38-Based Immunotherapy of Multiple Myeloma. Trends Cancer 6(1):9-12.

Konda P, Murphy JP, Gujar S (2020) Improving MHC-I Ligand Identification by Incorporating Targeted Searches of Mass Spectrometry Data. Methods in Molecular Biology 2120:161-171.

Lafreniere JD, Lehmann C. (2020) The curative effect of a cannabinoid 2 receptor agonist on functional failure and disruptive inflammation caused by intestinal ischemia and reperfusion. Fundam Clin Pharmacol. Feb;34(1):77-79. doi: 10.1111/fcp.12524.

Legge A, Blanchard C, Hanly JG (2020) Physical activity, sedentary behaviour and their associations with cardiovascular risk in systemic lupus erythematosus. Rheumatology May 1;59(5):1128-1136. doi: 10.1093/rheumatology/kez429.

Legge A, Kirkland S, Rockwood K, Andreou P, Bae SC, Gordon C, Romero-Diaz J, Sanchez-Guerrero J, Wallace DJ, Bernatsky S, Clarke AE, Merrill JT, Ginzler EM, Fortin PR, Gladman DD, Urowitz MB, Bruce IN, Isenberg DA, Rahman A, Alarcón GS, Petri M, Khamashta MA, Dooley MA, Ramsey-Goldman R, Manzi S, Zoma AA, Aranow C, Mackay M, Ruiz-Irastorza G, Lim SS, Inanc M, van Vollenhoven RF, Jonsen A, Nived O, Ramos-Casals M, Kamen DL, Kalunian KC, Jacobsen S, Peschken CA, Askanase A, Hanly JG. (2020) Prediction of Damage Accrual in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index. Arthritis and Rheumatology Apr;72(4):658-666. doi: 10.1002/art.41144.

Loh LC, Top KA. (2020) Of National Immunization Technical Advisory Groups (NITAGs), Evidence, and Decisions on Public Vaccination Programs: Lessons from Canada. Acta Med Port. Feb 3;33(2):90-92. doi: 10.20344/amp.12155.

McGuire C, Samargandi OA, Boudreau C, Whelan A, Bezuhly M. (2020) Prevention of Autologous Costal Cartilage Graft Warping in Secondary Rhinoplasty. Journal of Craniofacial Surgery Apr 7. doi: 10.1097/SCS.0000000000006429.

O'Brien MS, McDougall JJ. (2020) Neurophysiological assessment of joint nociceptors in the rat medial meniscus transection model of post-traumatic osteoarthritis. Osteoarthritis Cartilage. May 13:S1063-4584(20)31005-0. doi: 10.1016/j.joca.2020.05.004.

Omar T, Ziltener P, Chamberlain E, Cheng Z, Johnston B (2020) Mice Lacking γδ T Cells Exhibit Impaired Clearance of Pseudomonas aeruginosa Lung Infection and Excessive Production of Inflammatory Cytokines. Infection and Immunity 88(6):e00171-20.

Palau M, Piqué N, Comeau AM, Douglas GM, Ramírez-Lázaro MJ, Lario S, Calvet X, Langille MGI, Miñana-Galbis D. (2020) Detection of Helicobacter pylori Microevolution and Multiple Infection from Gastric Biopsies by Housekeeping Gene Amplicon Sequencing. Pathogens Feb 5;9(2):97. doi: 10.3390/pathogens9020097.

Philpott HT, McDougall JJ. (2020) Combatting joint pain and inflammation by dual inhibition of monoacylglycerol lipase and cyclooxygenase-2 in a rat model of osteoarthritis. Arthritis Research and Therapy Jan 14;22(1):9. doi: 10.1186/s13075-020-2096-3.

Rahim MMA, Parsons BD, Price EL, Slaine PD, Chilvers BL, Seaton GS, Wight A, Medina-Luna D, Dey S, Grandy SL, Anderson LE, Zamorano Cuervo N, Grandvaux N, Gaglia MM, Kelvin AA, Khaperskyy DA, McCormick C, Makrigiannis AP (2020) Defective influenza A virus RNA products mediate MAVS-dependent upregulation of human leukocyte antigen class I proteins. Journal of Virology Apr 22:JVI.00165-20. doi: 10.1128/JVI.00165-20.

Ralph R, Lew J, Zeng T, Francis M, Xue B, Roux M, Toloue Ostadgavahi A, Rubino S, Dawe NJ, Al-Ahdal MN, Kelvin DJ, Richardson CD, Kindrachuk J, Falzarano D, Kelvin AA. (2020) 2019-nCoV (Wuhan virus), a novel Coronavirus: human-to-human transmission, travel-related cases, and vaccine readiness. Journal of Infection in Developing Countries Jan 31;14(1):3-17. doi: 10.3855/jidc.12425.

Sharawy N, Lehmann C. (2020) Molecular mechanisms by which iNOS uncoupling can induce cardiovascular dysfunction during sepsis: Role of posttranslational modifications (PTMs). Life Sciences May 20;255:117821. doi: 10.1016/j.lfs.2020.117821. .

Slauenwhite D, McAlpine SM, Hanly JG, Malik A, Haidl ID, Marshall JS, Issekutz TB (2020) Association of a Type 2-Polarized T Cell Phenotype With Methotrexate Nonresponse in Patients With Rheumatoid Arthritis. Arthritis and Rheumatology Feb 10. doi: 10.1002/art.41223.

Tam J, Tran D, Bettinger JA, Moore D, Sauvé L, Jadavji T, Tan B, Vaudry W, Halperin SA, Top KA; Canadian Immunization Monitoring Program Active Investigators. (2020) Review of pediatric encephalitis and encephalopathy cases following immunization reported to the Canadian Immunization Monitoring Program Active (IMPACT) from 1992 to 2012. Vaccine Jun 9;38(28):4457-4463. doi: 10.1016/j.vaccine.2020.04.035.

Top KA, Esteghamati A, Kervin M, Henaff L, Graham JE, MacDonald NE (2020) Governing off-label vaccine use: An environmental scan of the Global National Immunization Technical Advisory Group Network. Vaccine Jan 29;38(5):1089-1095. doi: 10.1016/j.vaccine.2019.11.033.

Top KA, Righolt CH, Hawken S, Donelle J, Pabla G, Brna P, Deeks SL, Smith B, Wilson K, Mahmud SM (2020) Adverse Events Following Immunization Among Children With Epilepsy: A Self-Controlled Case Series. Pediatric Infectious Disease May;39(5):454-459. doi: 10.1097/INF.0000000000002553.

Top KA, Vaudry W, Morris SK, Pham-Huy A, Pernica JM, Tapiéro B, Gantt S, Price VE, Rassekh SR, Sung L, McConnell A, Rubin E, Chawla R, Halperin SA. (2020) Waning vaccine immunity and vaccination responses in children treated for acute lymphoblastic leukemia: A Canadian Immunization Research Network Study. Clinical Infectious Disease Feb 18:ciaa163. doi: 10.1093/cid/ciaa163.

Wight A, Parsons BD, Rahim MMA, Makrigiannis AP (2020) A Central Role for Ly49 Receptors in NK Cell Memory. Journal of Immunology Jun 1;204(11):2867-2875. doi: 10.4049/jimmunol.2000196.

Wu L, Zeng T, Deligios M, Milanesi L, Langille MGI, Zinellu A, Rubino S, Carru C, Kelvin DJ. (2020) Age-Related Variation of Bacterial and Fungal Communities in Different Body Habitats across the Young, Elderly, and Centenarians in Sardinia. mSphere Feb 26;5(1):e00558-19. doi: 10.1128/mSphere.00558-19.

Xue B, Zeng T, Jia L, Yang D, Lin SL, Sechi LA, Kelvin DJ. (2020) Identification of the distribution of human endogenous retroviruses K (HML-2) by PCR-based target enrichment sequencing. Retrovirology May 6;17(1):10. doi: 10.1186/s12977-020-00519-z.