Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines

Christina Sølund; Alexander P. Underwood; Carlota Fernandez-Antunez; Signe Bollerup; Lotte S. Mikkelsen; Signe Lysemose Villadsen; Ulrik Fahnøe; Anni Assing Winckelmann; Shan Feng; Caroline A. Nørløv Vinten; Magnus Illum Dalegaard; Greta Vizgirda; Anna Louise Sørensen; Santseharay Ramirez; Jens Bukh; Nina Weis

doi:10.3390/vaccines10010075

Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines

Christina Sølund, Alexander P. Underwood, Carlota Fernandez-Antunez, Signe Bollerup, Lotte S. Mikkelsen, Signe Lysemose Villadsen, Ulrik Fahnøe, Anni Assing Winckelmann, Shan Feng, Caroline A. Nørløv Vinten, Magnus Illum Dalegaard, Greta Vizgirda, Anna Louise Sørensen, Santseharay Ramirez, Jens Bukh, Nina Weis^*

^*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

13 Citationer (Scopus)

76 Downloads (Pure)

Abstract

With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty® or Spikevax®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID₅₀: 2525, IQR: 1667–4313) and vector–mRNA (ID₅₀: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID₅₀: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria® (p = 0.0072). Between mRNA–mRNA and vector– mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure.

Originalsprog	Engelsk
Artikelnummer	75
Tidsskrift	Vaccines
Vol/bind	10
Udgave nummer	1
ISSN	2076-393X
DOI	https://doi.org/10.3390/vaccines10010075
Status	Udgivet - 2022

Bibliografisk note

Funding Information:
This work was supported by grants from The Capital Region of Denmark?s Research Foundation (C.S., J.B.; 2020-A6936 and 2019-A6720), the Novo Nordisk Foundation (N.W., J.B.; NNF19OC0054518 and NNF19OC0055462), the Independent Research Fund Denmark (J.B.; 8020-00391B), the Candys Foundation (C.F-A., S.R., J.B.; 2018-269), The Danish Cancer Society (J.B.; R204-A12639), Manufacturer Vilhelm Pedersen and wife?s memorial scholarship (S.B), Master carpenter J?rgen Holm and wife Elisa. F. Hansen?s memorial scholarship (S.B.; 20006-1948) and the Danish Agency for Science and Higher Education (S.R., J.B.; 0237-00005B). J.B. is the 2015 recipient of the Novo Nordisk Prize and the 2019 recipient of a Distinguished Investigator grant from the Novo Nordisk Foundation.

Funding Information:
Funding: This work was supported by grants from The Capital Region of Denmark’s Research Foundation (C.S., J.B.; 2020-A6936 and 2019-A6720), the Novo Nordisk Foundation (N.W., J.B.; NNF19OC0054518 and NNF19OC0055462), the Independent Research Fund Denmark (J.B.; 8020-00391B), the Candys Foundation (C.F-A., S.R., J.B.; 2018-269), The Danish Cancer Society (J.B.; R204-A12639), Manufacturer Vilhelm Pedersen and wife’s memorial scholarship (S.B), Master carpenter Jørgen Holm and wife Elisa. F. Hansen’s memorial scholarship (S.B.; 20006-1948) and the Danish Agency for Science and Higher Education (S.R., J.B.; 0237-00005B). J.B. is the 2015 recipient of the Novo Nordisk Prize and the 2019 recipient of a Distinguished Investigator grant from the Novo Nordisk Foundation.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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Citationsformater

Sølund, C., Underwood, A. P., Fernandez-Antunez, C., Bollerup, S., Mikkelsen, L. S., Villadsen, S. L., Fahnøe, U., Winckelmann, A. A., Feng, S., Nørløv Vinten, C. A., Dalegaard, M. I., Vizgirda, G., Sørensen, A. L., Ramirez, S., Bukh, J., & Weis, N. (2022). Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines. Vaccines, 10(1), Artikel 75. https://doi.org/10.3390/vaccines10010075

Sølund, C, Underwood, AP, Fernandez-Antunez, C, Bollerup, S, Mikkelsen, LS, Villadsen, SL, Fahnøe, U , Winckelmann, AA, Feng, S, Nørløv Vinten, CA, Dalegaard, MI, Vizgirda, G, Sørensen, AL, Ramirez, S , Bukh, J & Weis, N 2022, 'Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines', Vaccines, bind 10, nr. 1, 75. https://doi.org/10.3390/vaccines10010075

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title = "Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines",

abstract = "With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty{\textregistered}, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria{\textregistered}, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty{\textregistered} or Spikevax{\textregistered}, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID50: 2525, IQR: 1667–4313) and vector–mRNA (ID50: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID50: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria{\textregistered} (p = 0.0072). Between mRNA–mRNA and vector– mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure.",

keywords = "COVID-19, MRNA vaccine, Neutralization/neutralisation, Neutralizing/neutralising antibodies, SARS-CoV-2, Vector vaccine",

author = "Christina S{\o}lund and Underwood, {Alexander P.} and Carlota Fernandez-Antunez and Signe Bollerup and Mikkelsen, {Lotte S.} and Villadsen, {Signe Lysemose} and Ulrik Fahn{\o}e and Winckelmann, {Anni Assing} and Shan Feng and {N{\o}rl{\o}v Vinten}, {Caroline A.} and Dalegaard, {Magnus Illum} and Greta Vizgirda and S{\o}rensen, {Anna Louise} and Santseharay Ramirez and Jens Bukh and Nina Weis",

note = "Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

doi = "10.3390/vaccines10010075",

language = "English",

volume = "10",

journal = "Vaccines",

issn = "2076-393X",

publisher = "MDPI AG",

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T1 - Analysis of Neutralization Titers against SARS-CoV-2 in Health-Care Workers Vaccinated with Prime-Boost mRNA–mRNA or Vector–mRNA COVID-19 Vaccines

AU - Sølund, Christina

AU - Underwood, Alexander P.

AU - Fernandez-Antunez, Carlota

AU - Bollerup, Signe

AU - Mikkelsen, Lotte S.

AU - Villadsen, Signe Lysemose

AU - Fahnøe, Ulrik

AU - Winckelmann, Anni Assing

AU - Feng, Shan

AU - Nørløv Vinten, Caroline A.

AU - Dalegaard, Magnus Illum

AU - Vizgirda, Greta

AU - Sørensen, Anna Louise

AU - Ramirez, Santseharay

AU - Bukh, Jens

AU - Weis, Nina

PY - 2022

Y1 - 2022

N2 - With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty® or Spikevax®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID50: 2525, IQR: 1667–4313) and vector–mRNA (ID50: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID50: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria® (p = 0.0072). Between mRNA–mRNA and vector– mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure.

AB - With increasing numbers of vaccine-breakthrough infections worldwide, assessing the immunogenicity of vaccinated health-care workers that are frequently exposed to SARS-CoV-2-infected individuals is important. In this study, neutralization titers against SARS-CoV-2 were assessed one month after completed prime-boost vaccine regimens in health-care workers vaccinated with either mRNA–mRNA (Comirnaty®, BioNTech-Pfzier, Mainz, Germany/New York, NY, USA, n = 98) or vector-based (Vaxzevria®, Oxford-AstraZeneca, Cambridge, UK) followed by mRNA-based (Comirnaty® or Spikevax®, Moderna, Cambridge, MA, USA) vaccines (n = 16). Vaccine-induced neutralization titers were compared to time-matched, unvaccinated individuals that were infected with SARS-CoV-2 and presented with mild symptoms (n = 38). Significantly higher neutralizing titers were found in both the mRNA–mRNA (ID50: 2525, IQR: 1667–4313) and vector–mRNA (ID50: 4978, IQR: 3364–7508) prime-boost vaccine regimens when compared to SARS-CoV-2 infection (ID50: 401, IQR: 271–792) (p < 0.0001). However, infection with SARS-CoV-2 induced higher titers when compared to a single dose of Vaxzevria® (p = 0.0072). Between mRNA–mRNA and vector– mRNA prime-boost regimens, the vector–mRNA vaccine regimen induced higher neutralization titers (p = 0.0054). Demographically, both age and time between vaccination doses were associated with vaccine-induced neutralization titers (p = 0.02 and p = 0.03, respectively). This warrants further investigation into the optimal time to administer booster vaccination for optimized induction of neutralizing responses. Although anecdotal (n = 3), those with exposure to SARS-CoV-2, either before or after vaccination, demonstrated superior neutralizing titers, which is suggestive of further boosting through viral exposure.

KW - COVID-19

KW - MRNA vaccine

KW - Neutralization/neutralisation

KW - Neutralizing/neutralising antibodies

KW - SARS-CoV-2

KW - Vector vaccine

U2 - 10.3390/vaccines10010075

DO - 10.3390/vaccines10010075

M3 - Journal article

C2 - 35062736

AN - SCOPUS:85122722452

SN - 2076-393X

VL - 10

JO - Vaccines

JF - Vaccines

IS - 1

M1 - 75

ER -