Andrew H Karaba1, Xianming Zhu2, Sarah E Benner2, Olivia Akinde2, Yolanda Eby2, Kristy H Wang1, Sharada Saraf3, Jacqueline M Garonzik-Wang4, Sabra L Klein1,5, Justin R Bailey1, Andrea L Cox1,5,6, Joel N Blankson1, Christine M Durand1, Dorry L Segev4, William A Werbel1, Aaron A R Tobian2. 1. Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD. 2. Department of Pathology, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD. 3. Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Baltimore, MD. 4. Department of Surgery, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD. 5. W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD. 6. Bloomberg Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, MD.
Abstract
BACKGROUND: Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if prevaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination. METHODS: A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, and comparison to 16 healthy controls (HCs). Antispike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detection-based multiplexed sandwich immunoassays (Meso Scale Diagnostics) were used to quantify plasma cytokine and chemokine concentrations (n = 20 analytes) and compare concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine using Wilcoxon-rank-sum test with false discovery rates computed to correct for multiple comparisons. RESULTS: In the study population, 100% of HCs, 59% of SOTRs after 2 doses and 63% of SOTRs after 3 doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in baseline cytokine levels between SOTRs with high versus low-titer antibodies after 2 doses of vaccine. However, as compared with poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher prethird dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1α, and TNF-α (false discovery rates < 0.05). CONCLUSIONS: A specific inflammatory profile may be associated with developing higher antibodies in response to a third dose of SARS-CoV-2 vaccine in SOTRs.
BACKGROUND: Solid organ transplant recipients (SOTRs) are at increased risk for severe COVID-19 and exhibit lower antibody responses to SARS-CoV-2 vaccines. This study aimed to determine if prevaccination cytokine levels are associated with antibody response to SARS-CoV-2 vaccination. METHODS: A cross-sectional study was performed among 58 SOTRs before and after two-dose mRNA vaccine series, 35 additional SOTRs before and after a third vaccine dose, and comparison to 16 healthy controls (HCs). Antispike antibody was assessed using the IgG Euroimmun ELISA. Electrochemiluminescence detection-based multiplexed sandwich immunoassays (Meso Scale Diagnostics) were used to quantify plasma cytokine and chemokine concentrations (n = 20 analytes) and compare concentrations between SOTRs and HCs, stratified by ultimate antibody response to the vaccine using Wilcoxon-rank-sum test with false discovery rates computed to correct for multiple comparisons. RESULTS: In the study population, 100% of HCs, 59% of SOTRs after 2 doses and 63% of SOTRs after 3 doses had a detectable antibody response. Multiple baseline cytokines were elevated in SOTRs versus HCs. There was no significant difference in baseline cytokine levels between SOTRs with high versus low-titer antibodies after 2 doses of vaccine. However, as compared with poor antibody responders, SOTRs who went on to develop a high-titer antibody response to a third dose of vaccine had significantly higher prethird dose levels of several innate immune cytokines including IL-17, IL-2Ra, IL-6, IP-10, MIP-1α, and TNF-α (false discovery rates < 0.05). CONCLUSIONS: A specific inflammatory profile may be associated with developing higher antibodies in response to a third dose of SARS-CoV-2 vaccine in SOTRs.
Authors: Inna G Ovsyannikova; Karlene C Reid; Robert M Jacobson; Ann L Oberg; George G Klee; Gregory A Poland Journal: Vaccine Date: 2003-09-08 Impact factor: 3.641
Authors: Andrew H Karaba; Xianming Zhu; Tao Liang; Kristy H Wang; Alex G Rittenhouse; Olivia Akinde; Yolanda Eby; Jessica E Ruff; Joel N Blankson; Aura T Abedon; Jennifer L Alejo; Andrea L Cox; Justin R Bailey; Elizabeth A Thompson; Sabra L Klein; Daniel S Warren; Jacqueline M Garonzik-Wang; Brian J Boyarsky; Ioannis Sitaras; Andrew Pekosz; Dorry L Segev; Aaron A R Tobian; William A Werbel Journal: Am J Transplant Date: 2022-01-18 Impact factor: 8.086
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Authors: Kizzmekia S Corbett; Barbara Flynn; Kathryn E Foulds; Joseph R Francica; Seyhan Boyoglu-Barnum; Anne P Werner; Britta Flach; Sarah O'Connell; Kevin W Bock; Mahnaz Minai; Bianca M Nagata; Hanne Andersen; David R Martinez; Amy T Noe; Naomi Douek; Mitzi M Donaldson; Nadesh N Nji; Gabriela S Alvarado; Darin K Edwards; Dillon R Flebbe; Evan Lamb; Nicole A Doria-Rose; Bob C Lin; Mark K Louder; Sijy O'Dell; Stephen D Schmidt; Emily Phung; Lauren A Chang; Christina Yap; John-Paul M Todd; Laurent Pessaint; Alex Van Ry; Shanai Browne; Jack Greenhouse; Tammy Putman-Taylor; Amanda Strasbaugh; Tracey-Ann Campbell; Anthony Cook; Alan Dodson; Katelyn Steingrebe; Wei Shi; Yi Zhang; Olubukola M Abiona; Lingshu Wang; Amarendra Pegu; Eun Sung Yang; Kwanyee Leung; Tongqing Zhou; I-Ting Teng; Alicia Widge; Ingelise Gordon; Laura Novik; Rebecca A Gillespie; Rebecca J Loomis; Juan I Moliva; Guillaume Stewart-Jones; Sunny Himansu; Wing-Pui Kong; Martha C Nason; Kaitlyn M Morabito; Tracy J Ruckwardt; Julie E Ledgerwood; Martin R Gaudinski; Peter D Kwong; John R Mascola; Andrea Carfi; Mark G Lewis; Ralph S Baric; Adrian McDermott; Ian N Moore; Nancy J Sullivan; Mario Roederer; Robert A Seder; Barney S Graham Journal: N Engl J Med Date: 2020-07-28 Impact factor: 91.245
Authors: Victoria G Hall; Victor H Ferreira; Terrance Ku; Matthew Ierullo; Beata Majchrzak-Kita; Cecilia Chaparro; Nazia Selzner; Jeffrey Schiff; Michael McDonald; George Tomlinson; Vathany Kulasingam; Deepali Kumar; Atul Humar Journal: N Engl J Med Date: 2021-08-11 Impact factor: 91.245
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Authors: Jane C Figueiredo; Fred R Hirsch; Lawrence H Kushi; Wendy N Nembhard; James M Crawford; Nicholas Mantis; Laurel Finster; Noah M Merin; Akil Merchant; Karen L Reckamp; Gil Y Melmed; Jonathan Braun; Dermot McGovern; Samir Parekh; Douglas A Corley; Namvar Zohoori; Benjamin C Amick; Ruofei Du; Peter K Gregersen; Betty Diamond; Emanuela Taioli; Carlos Sariol; Ana Espino; Daniela Weiskopf; Alba Gifoni; James Brien; William Hanege; Marc Lipsitch; David A Zidar; Ann Scheck McAlearney; Ania Wajnberg; Joshua LaBaer; E Yvonne Lewis; Raquel A Binder; Ann M Moormann; Catherine Forconi; Sarah Forrester; Jennifer Batista; John Schieffelin; Dongjoo Kim; Giulia Biancon; Jennifer VanOudenhove; Stephanie Halene; Rong Fan; Dan H Barouch; Galit Alter; Swetha Pinninti; Suresh B Boppana; Sunil K Pati; Misty Latting; Andrew H Karaba; John Roback; Rafick Sekaly; Andrew Neish; Ahnalee M Brincks; Douglas A Granger; Amy B Karger; Bharat Thyagarajan; Stefani N Thomas; Sabra L Klein; Andrea L Cox; Todd Lucas; Debra Furr-Holden; Kent Key; Nicole Jones; Jens Wrammerr; Mehul Suthar; Serre Yu Wong; Natalie M Bowman; Viviana Simon; Lynne D Richardson; Russell McBride; Florian Krammer; Meenakshi Rana; Joshua Kennedy; Karl Boehme; Craig Forrest; Steve W Granger; Christopher D Heaney; Maria Knight Lapinski; Shannon Wallet; Ralph S Baric; Luca Schifanella; Marcos Lopez; Soledad Fernández; Eben Kenah; Ashish R Panchal; William J Britt; Iñaki Sanz; Madhav Dhodapkar; Rafi Ahmed; Luther A Bartelt; Alena J Markmann; Jessica T Lin; Robert S Hagan; Matthew C Wolfgang; Jacek Skarbinski Journal: Open Forum Infect Dis Date: 2022-04-27 Impact factor: 4.423