Project Description:

As we get older our risk of developing serious respiratory infections increases. Concurrently, the aging immune system is continually remodelled by environmental exposures, infections, medications, and chronic conditions such as frailty. We aim to understand how the aging immune system impacts responses to vaccination and infection.

Our ongoing investigations include;

1. Quantitating immune responses to vaccination (i.e., COVID-19, and others) in older adults including older adults living in long-term care
2. Discovering how immunomodulatory drugs impact vaccination responses.
3. Using pre-clinical models to understand how immune responses to bacterial pneumonia change with age.

Team Members:
Technical lead: Braeden Cowborough
Post-doctoral fellow: Dr Jessica Breznik
Graduate students: Jenna Benoit (PhD candidate)

Publications:

1.	Immunomodulatory drugs have divergent effects on humoral and cellular immune responses to SARS-CoV-2 vaccination in people living with rheumatoid arthritis. Benoit JM, Breznik JA, Ang JC, Bhakta H, Huynh A, Cowbrough B, Baker B, Heessels L, Lodhi S, Yan E, Ewusie J, Nazy I, Bramson J, Miller MS, Bernatsky S, Larché MJ, Bowdish DME; SUCCEED Investigator Group. Sci Rep. 2023 Dec 21;13(1):22846. doi: 10.1038/s41598-023-50263-5. PMID: 38129594 Free PMC article.
2.	Early humoral and cellular responses after bivalent SARS-CoV-2 mRNA-1273.214 vaccination in long-term care and retirement home residents in Ontario, Canada: An observational cohort study. Breznik JA, Rahim A, Bhakta H, Clare R, Zhang A, Ang J, Stacey HD, Liu LM, Kennedy A, Bilaver L, Hagerman M, Kajaks T, Bramson JL, Nazy I, Miller MS, Costa AP, Bowdish DME; COVID in LTC Investigator Group. J Med Virol. 2023 Oct;95(10):e29170. doi: 10.1002/jmv.29170. PMID: 37822054
3.	Early Omicron infection is associated with increased reinfection risk in older adults in long-term care and retirement facilities. Breznik JA, Rahim A, Zhang A, Ang J, Stacey HD, Bhakta H, Clare R, Liu LM, Kennedy A, Hagerman M, Kajaks T, Miller MS, Nazy I, Bramson JL, Costa AP, Bowdish DME. EClinicalMedicine. 2023 Aug 21;63:102148. doi: 10.1016/j.eclinm.2023.102148. eCollection 2023 Sep. PMID: 37753447 Free PMC article.
4.	Protocol for a living evidence synthesis on variants of concern and COVID-19 vaccine effectiveness. Shaver N, Katz M, Darko Asamoah G, Linkins LA, Abdelkader W, Beck A, Bennett A, Hughes SE, Smith M, Begin M, Coyle D, Piggott T, Kagina BM, Welch V, Colijn C, Earn DJD, El Emam K, Heffernan J, O’Brien SF, Wilson K, Collins E, Navarro T, Beyene J, Boutron I, Bowdish D, Cooper C, Costa A, Curran J, Griffith L, Hsu A, Grimshaw J, Langlois MA, Li X, Pham-Huy A, Raina P, Rubini M, Thabane L, Wang H, Xu L, Brouwers M, Horsley T, Lavis J, Iorio A, Little J. Vaccine. 2023 Oct 13;41(43):6411-6418. doi: 10.1016/j.vaccine.2023.09.012. Epub 2023 Sep 16. PMID: 37718186 Review.
5.	Protection from Omicron Infection in Residents of Nursing and Retirement Homes in Ontario, Canada. Breznik JA, Rahim A, Kajaks T, Hagerman M, Bilaver L, Colwill K, Dayam RM, Gingras AC, Verschoor CP, McElhaney JE, Bramson JL, Bowdish DME, Costa AP. J Am Med Dir Assoc. 2023 May;24(5):753-758. doi: 10.1016/j.jamda.2023.02.105. Epub 2023 Mar 28. PMID: 37001559 Free PMC article.
6.	Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study. MacFadden DR, Maxwell C, Bowdish D, Bronskill S, Brooks J, Brown K, Burrows LL, Clarke A, Langford B, Leung E, Leung V, Manuel D, McGeer A, Mishra S, Morris AM, Nott C, Raybardhan S, Sapin M, Schwartz KL, So M, Soucy JR, Daneman N. Clin Infect Dis. 2023 Aug 14;77(3):362-370. doi: 10.1093/cid/ciad190. PMID: 36999314 Free PMC article.
7.	Comparison of three dosing intervals for the primary vaccination of the SARS-CoV-2 mRNA Vaccine (BNT162b2) on magnitude, neutralization capacity and durability of the humoral immune response in health care workers: A prospective cohort study. Leong DP, Zhang A, Breznik JA, Clare R, Huynh A, Mushtaha M, Rangarajan S, Stacey H, Kim PY, Loeb M, Denburg JA, Mertz D, Chagla Z, Nazy I, Miller MS, Bowdish DME, Duong M. PLoS One. 2023 Feb 15;18(2):e0281673. doi: 10.1371/journal.pone.0281673. eCollection 2023. PMID: 36791069 Free PMC article.
8.	Cytomegalovirus Seropositivity in Older Adults Changes the T Cell Repertoire but Does Not Prevent Antibody or Cellular Responses to SARS-CoV-2 Vaccination. Breznik JA, Huynh A, Zhang A, Bilaver L, Bhakta H, Stacey HD, Ang JC, Bramson JL, Nazy I, Miller MS, Denburg J, Costa AP, Bowdish DME; other members of the COVID-in-LTC Investigator Group. J Immunol. 2022 Nov 15;209(10):1892-1905. doi: 10.4049/jimmunol.2200369. PMID: 36426948 Free PMC article.
9.	Seropositivity and risk factors for SARS-CoV-2 infection in a South Asian community in Ontario: a cross-sectional analysis of a prospective cohort study. Anand SS, Arnold C, Bangdiwala SI, Bolotin S, Bowdish D, Chanchlani R, de Souza RJ, Desai D, Kandasamy S, Khan F, Khan Z, Langlois MA, Limbachia J, Lear SA, Loeb M, Loh L, Manoharan B, Nakka K, Pelchat M, Punthakee Z, Schulze KM, Williams N, Wahi G. CMAJ Open. 2022 Jul 5;10(3):E599-E609. doi: 10.9778/cmajo.20220031. Print 2022 Jul-Sep. PMID: 35790229 Free PMC article.
10.	Erythro-VLPs: Anchoring SARS-CoV-2 spike proteins in erythrocyte liposomes. Himbert S, Gastaldo IP, Ahmed R, Pomier KM, Cowbrough B, Jahagirdar D, Ros S, Juhasz J, Stöver HDH, Ortega J, Melacini G, Bowdish DME, Rheinstädter MC. PLoS One. 2022 Mar 11;17(3):e0263671. doi: 10.1371/journal.pone.0263671. eCollection 2022. PMID: 35275926 Free PMC article.
11.	Antibody Responses to Third-Dose mRNA Vaccines in Nursing Home and Assisted Living Residents. Zhang A, Breznik JA, Clare R, Nazy I, Miller MS, Bowdish DME, Costa AP. J Am Med Dir Assoc. 2022 Mar;23(3):444-446. doi: 10.1016/j.jamda.2021.12.035. Epub 2022 Jan 15. PMID: 35041829 Free PMC article. No abstract available.
12.	Antibody Responses 3-5 Months Post-Vaccination with mRNA-1273 or BNT163b2 in Nursing Home Residents. Breznik JA, Zhang A, Huynh A, Miller MS, Nazy I, Bowdish DME, Costa AP. J Am Med Dir Assoc. 2021 Dec;22(12):2512-2514. doi: 10.1016/j.jamda.2021.10.001. Epub 2021 Nov 1. PMID: 34736891 Free PMC article. No abstract available.
13.	DNA methylation patterns are related to co-morbidity status and circulating C-reactive protein levels in the nursing home elderly. Verschoor CP, McEwen LM, Kobor MS, Loeb MB, Bowdish DME. Exp Gerontol. 2018 May;105:47-52. doi: 10.1016/j.exger.2017.10.010. Epub 2017 Oct 12. PMID: 29032243
14.	Serum C-Reactive Protein and Congestive Heart Failure as Significant Predictors of Herpes Zoster Vaccine Response in Elderly Nursing Home Residents. Verschoor CP, Lelic A, Parsons R, Evelegh C, Bramson JL, Johnstone J, Loeb MB, Bowdish DME. J Infect Dis. 2017 Jul 15;216(2):191-197. doi: 10.1093/infdis/jix257. PMID: 28838148 Free PMC article.
15.	Immunogenicity of Varicella Vaccine and Immunologic Predictors of Response in a Cohort of Elderly Nursing Home Residents. Lelic A, Verschoor CP, Lau VW, Parsons R, Evelegh C, Bowdish DM, Bramson JL, Loeb MB. J Infect Dis. 2016 Dec 15;214(12):1905-1910. doi: 10.1093/infdis/jiw462. Epub 2016 Oct 5. PMID: 27707807
16.	Broadly Neutralizing Hemagglutinin Stalk-Specific Antibodies Induce Potent Phagocytosis of Immune Complexes by Neutrophils in an Fc-Dependent Manner. Mullarkey CE, Bailey MJ, Golubeva DA, Tan GS, Nachbagauer R, He W, Novakowski KE, Bowdish DM, Miller MS, Palese P. mBio. 2016 Oct 4;7(5):e01624-16. doi: 10.1128/mBio.01624-16. PMID: 27703076 Free PMC article.
17.	Privileged Antigen Presentation in Splenic B Cell Follicles Maximizes T Cell Responses in Prime-Boost Vaccination. Bridle BW, Nguyen A, Salem O, Zhang L, Koshy S, Clouthier D, Chen L, Pol J, Swift SL, Bowdish DM, Lichty BD, Bramson JL, Wan Y. J Immunol. 2016 Jun 1;196(11):4587-95. doi: 10.4049/jimmunol.1600106. Epub 2016 Apr 27. PMID: 27183620
18.	Microneutralization assay titres correlate with protection against seasonal influenza H1N1 and H3N2 in children. Verschoor CP, Singh P, Russell ML, Bowdish DM, Brewer A, Cyr L, Ward BJ, Loeb M. PLoS One. 2015 Jun 24;10(6):e0131531. doi: 10.1371/journal.pone.0131531. eCollection 2015. PMID: 26107625 Free PMC article. Clinical Trial.
19.	Immunosenescence and novel vaccination strategies for the elderly. Dorrington MG, Bowdish DM. Front Immunol. 2013 Jun 28;4:171. doi: 10.3389/fimmu.2013.00171. Print 2013. PMID: 23825474 Free PMC article.
20.	The polyfunctionality of human memory CD8+ T cells elicited by acute and chronic virus infections is not influenced by age. Lelic A, Verschoor CP, Ventresca M, Parsons R, Evelegh C, Bowdish D, Betts MR, Loeb MB, Bramson JL. PLoS Pathog. 2012;8(12):e1003076. doi: 10.1371/journal.ppat.1003076. Epub 2012 Dec 13. PMID: 23271970 Free PMC article. Clinical Trial.