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Anti-PEG Antibodies Boosted in Humans by SARS-CoV-2 Lipid Nanoparticle mRNA Vaccine.
Ju, Yi; Lee, Wen Shi; Pilkington, Emily H; Kelly, Hannah G; Li, Shiyao; Selva, Kevin J; Wragg, Kathleen M; Subbarao, Kanta; Nguyen, Thi H O; Rowntree, Louise C; Allen, Lilith F; Bond, Katherine; Williamson, Deborah A; Truong, Nghia P; Plebanski, Magdalena; Kedzierska, Katherine; Mahanty, Siddhartha; Chung, Amy W; Caruso, Frank; Wheatley, Adam K; Juno, Jennifer A; Kent, Stephen J.
  • Ju Y; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Lee WS; School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
  • Pilkington EH; Department of Chemical Engineering, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Kelly HG; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Li S; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Selva KJ; Department of Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3000, Australia.
  • Wragg KM; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Subbarao K; Department of Chemical Engineering, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Nguyen THO; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Rowntree LC; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Allen LF; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Bond K; WHO Collaborating Centre for Reference and Research on Influenza, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC 3000, Australia.
  • Williamson DA; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Truong NP; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Plebanski M; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Kedzierska K; Department of Microbiology, Royal Melbourne Hospital, Melbourne, VIC 3000, Australia.
  • Mahanty S; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Chung AW; Department of Microbiology, Royal Melbourne Hospital, Melbourne, VIC 3000, Australia.
  • Caruso F; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
  • Wheatley AK; Department of Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3000, Australia.
  • Juno JA; School of Health and Biomedical Sciences, RMIT University, Bundoora, VIC 3083, Australia.
  • Kent SJ; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3000, Australia.
ACS Nano ; 16(8): 11769-11780, 2022 Aug 23.
Article in English | MEDLINE | ID: covidwho-1908087
ABSTRACT
Humans commonly have low level antibodies to poly(ethylene) glycol (PEG) due to environmental exposure. Lipid nanoparticle (LNP) mRNA vaccines for SARS-CoV-2 contain small amounts of PEG, but it is not known whether PEG antibodies are enhanced by vaccination and what their impact is on particle-immune cell interactions in human blood. We studied plasma from 130 adults receiving either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) mRNA vaccines or no SARS-CoV-2 vaccine for PEG-specific antibodies. Anti-PEG IgG was commonly detected prior to vaccination and was significantly boosted a mean of 13.1-fold (range 1.0-70.9) following mRNA-1273 vaccination and a mean of 1.78-fold (range 0.68-16.6) following BNT162b2 vaccination. Anti-PEG IgM increased 68.5-fold (range 0.9-377.1) and 2.64-fold (0.76-12.84) following mRNA-1273 and BNT162b2 vaccination, respectively. The rise in PEG-specific antibodies following mRNA-1273 vaccination was associated with a significant increase in the association of clinically relevant PEGylated LNPs with blood phagocytes ex vivo. PEG antibodies did not impact the SARS-CoV-2 specific neutralizing antibody response to vaccination. However, the elevated levels of vaccine-induced anti-PEG antibodies correlated with increased systemic reactogenicity following two doses of vaccination. We conclude that PEG-specific antibodies can be boosted by LNP mRNA vaccination and that the rise in PEG-specific antibodies is associated with systemic reactogenicity and an increase of PEG particle-leukocyte association in human blood. The longer-term clinical impact of the increase in PEG-specific antibodies induced by lipid nanoparticle mRNA vaccines should be monitored. It may be useful to identify suitable alternatives to PEG for developing next-generation LNP vaccines to overcome PEG immunogenicity in the future.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Vaccines / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Adult / Humans Language: English Journal: ACS Nano Year: 2022 Document Type: Article Affiliation country: Acsnano.2c04543

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Vaccines / COVID-19 Type of study: Prognostic study Topics: Vaccines Limits: Adult / Humans Language: English Journal: ACS Nano Year: 2022 Document Type: Article Affiliation country: Acsnano.2c04543