Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine

Yi Ju; Wen Shi Lee; Emily H Pilkington; Hannah G Kelly; Shiyao Li; Kevin J Selva; Kathleen M Wragg; Kanta Subbarao; Thi H O Nguyen; Louise C Rowntree; Lilith F Allen; Katherine Bond; Deborah A Williamson; Nghia P Truong; Magdalena Plebanski; Katherine Kedzierska; Siddhartha Mahanty; Amy W Chung; Frank Caruso; Adam K Wheatley; Jennifer A Juno; Stephen J Kent

doi:10.1021/acsnano.2c04543

Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine

Yi Ju^*, Wen Shi Lee, Emily H Pilkington, Hannah G Kelly, Shiyao Li, Kevin J Selva, Kathleen M Wragg, Kanta Subbarao, Thi H O Nguyen, Louise C Rowntree, Lilith F Allen, Katherine Bond, Deborah A Williamson, Nghia P Truong, Magdalena Plebanski, Katherine Kedzierska, Siddhartha Mahanty, Amy W Chung, Frank Caruso, Adam K WheatleyJennifer A Juno, Stephen J Kent

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	11769-11780
Number of pages	12
Journal	ACS Nano
Volume	16
Issue number	8
Early online date	27 Jun 2022
DOIs	https://doi.org/10.1021/acsnano.2c04543
Publication status	Published - 23 Aug 2022

Keywords

Adult
Humans
COVID-19 vaccines
BNT162 vaccine
SARS-CoV-2
COVID-19/prevention & control
Polyethylene glycols
Antibodies
Vaccination
Antibodies, Viral
Antibodies, Neutralizing
mRNA vaccines

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsnano.2c04543

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Ju, Y., Lee, W. S., Pilkington, E. H., Kelly, H. G., Li, S., Selva, K. J., Wragg, K. M., Subbarao, K., Nguyen, T. H. O., Rowntree, L. C., Allen, L. F., Bond, K., Williamson, D. A., Truong, N. P., Plebanski, M., Kedzierska, K., Mahanty, S., Chung, A. W., Caruso, F., ... Kent, S. J. (2022). Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine. ACS Nano, 16(8), 11769-11780. https://doi.org/10.1021/acsnano.2c04543

@article{b200e71e99cf4decbd8ab31a83895c40,

title = "Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine",

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.",

keywords = "Adult, Humans, COVID-19 vaccines, BNT162 vaccine, SARS-CoV-2, COVID-19/prevention & control, Polyethylene glycols, Antibodies, Vaccination, Antibodies, Viral, Antibodies, Neutralizing, mRNA vaccines",

author = "Yi Ju and Lee, {Wen Shi} and Pilkington, {Emily H} and Kelly, {Hannah G} and Shiyao Li and Selva, {Kevin J} and Wragg, {Kathleen M} and Kanta Subbarao and Nguyen, {Thi H O} and Rowntree, {Louise C} and Allen, {Lilith F} and Katherine Bond and Williamson, {Deborah A} and Truong, {Nghia P} and Magdalena Plebanski and Katherine Kedzierska and Siddhartha Mahanty and Chung, {Amy W} and Frank Caruso and Wheatley, {Adam K} and Juno, {Jennifer A} and Kent, {Stephen J}",

note = "Funding: This work was supported by the Australian National Health and Medical Research Council (NHMRC) fellowship or leadership awards to S.J.K., K.K., J.A.J., A.K.W., F.C., A.W.C.,D.A.W., K.S. and T.H.O.N.; RMIT Vice Chancellor{\textquoteright}s Postdoctoral Fellowship to Y.J.; the Australian Medical Research Future Fund award #2005544 to K.K., S.J.K., J.A.J.,A.K.W., A.W.C. and D.A.W.; Australian Research Council awards DP210103114 and DP200100231 to F.C., N.P.T.,S.J.K., Y.J., and A.K.W., and NHMRC award 1149990 to S.J.K.and F.C.",

year = "2022",

month = aug,

day = "23",

doi = "10.1021/acsnano.2c04543",

language = "English",

volume = "16",

pages = "11769--11780",

journal = "ACS Nano",

issn = "1936-0851",

publisher = "American Chemical Society (ACS)",

number = "8",

}

Ju, Y, Lee, WS, Pilkington, EH, Kelly, HG, Li, S, Selva, KJ, Wragg, KM, Subbarao, K, Nguyen, THO, Rowntree, LC, Allen, LF, Bond, K, Williamson, DA, Truong, NP, Plebanski, M, Kedzierska, K, Mahanty, S, Chung, AW, Caruso, F, Wheatley, AK, Juno, JA & Kent, SJ 2022, 'Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine', ACS Nano, vol. 16, no. 8, pp. 11769-11780. https://doi.org/10.1021/acsnano.2c04543

TY - JOUR

T1 - Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine

AU - Ju, Yi

AU - Lee, Wen Shi

AU - Pilkington, Emily H

AU - Kelly, Hannah G

AU - Li, Shiyao

AU - Selva, Kevin J

AU - Wragg, Kathleen M

AU - Subbarao, Kanta

AU - Nguyen, Thi H O

AU - Rowntree, Louise C

AU - Allen, Lilith F

AU - Bond, Katherine

AU - Williamson, Deborah A

AU - Truong, Nghia P

AU - Plebanski, Magdalena

AU - Kedzierska, Katherine

AU - Mahanty, Siddhartha

AU - Chung, Amy W

AU - Caruso, Frank

AU - Wheatley, Adam K

AU - Juno, Jennifer A

AU - Kent, Stephen J

N1 - Funding: This work was supported by the Australian National Health and Medical Research Council (NHMRC) fellowship or leadership awards to S.J.K., K.K., J.A.J., A.K.W., F.C., A.W.C.,D.A.W., K.S. and T.H.O.N.; RMIT Vice Chancellor’s Postdoctoral Fellowship to Y.J.; the Australian Medical Research Future Fund award #2005544 to K.K., S.J.K., J.A.J.,A.K.W., A.W.C. and D.A.W.; Australian Research Council awards DP210103114 and DP200100231 to F.C., N.P.T.,S.J.K., Y.J., and A.K.W., and NHMRC award 1149990 to S.J.K.and F.C.

PY - 2022/8/23

Y1 - 2022/8/23

N2 - 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.

AB - 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.

KW - Adult

KW - Humans

KW - COVID-19 vaccines

KW - BNT162 vaccine

KW - SARS-CoV-2

KW - COVID-19/prevention & control

KW - Polyethylene glycols

KW - Antibodies

KW - Vaccination

KW - Antibodies, Viral

KW - Antibodies, Neutralizing

KW - mRNA vaccines

U2 - 10.1021/acsnano.2c04543

DO - 10.1021/acsnano.2c04543

M3 - Article

C2 - 35758934

SN - 1936-0851

VL - 16

SP - 11769

EP - 11780

JO - ACS Nano

JF - ACS Nano

IS - 8

ER -

Anti-PEG antibodies boosted in humans by SARS-CoV-2 lipid nanoparticle mRNA vaccine

Abstract

Keywords

UN SDGs

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