Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines
•vaccine induced higher Surrogate neutralizing antibody and RBD-targeted B cell responses were greater after mRNA compared to vector vaccine.•Although vector vaccine boosted antibodies against human Adenovirus, those titres did not correlate with anti-spike titres.•Further work is needed to improve...
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| Published in | Vaccine Vol. 41; no. 48; pp. 7192 - 7200 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
22.11.2023
Elsevier Limited |
| Subjects | |
| Online Access | Get full text |
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| Abstract | •vaccine induced higher Surrogate neutralizing antibody and RBD-targeted B cell responses were greater after mRNA compared to vector vaccine.•Although vector vaccine boosted antibodies against human Adenovirus, those titres did not correlate with anti-spike titres.•Further work is needed to improve the immunogenicity of vector vaccines as they remain an important option for pandemic and outbreak responses.
Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10–48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies.
ClinicalTrials.gov Identifier: NCT05110911. |
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| AbstractList | Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911.Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911. •mRNA SARS-CoV-2 vaccine induced higher surrogate neutralizing antibody titres and a more potent, RBD-targeted B cell response than adenoviral vaccine.•Although adenoviral vaccine boosted antibodies against human Adenovirus, those titres did not correlate with anti-spike titres.•Further work is needed to improve the immunogenicity of viral vector vaccines as they remain an important option for pandemic and outbreak responses. Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10–48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911. Highlights•vaccine induced higher Surrogate neutralizing antibody and RBD-targeted B cell responses were greater after mRNA compared to vector vaccine. •Although vector vaccine boosted antibodies against human Adenovirus, those titres did not correlate with anti-spike titres. •Further work is needed to improve the immunogenicity of vector vaccines as they remain an important option for pandemic and outbreak responses. •vaccine induced higher Surrogate neutralizing antibody and RBD-targeted B cell responses were greater after mRNA compared to vector vaccine.•Although vector vaccine boosted antibodies against human Adenovirus, those titres did not correlate with anti-spike titres.•Further work is needed to improve the immunogenicity of vector vaccines as they remain an important option for pandemic and outbreak responses. Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10–48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911. Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10–48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies.ClinicalTrials.gov Identifier: NCT05110911. Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of this study was to validate whether immunogenicity differs for adenoviral vectored (AdV) versus mRNA vaccines against SARS-CoV-2, and to investigate how anti-vector immunity and B cell dynamics modulate immunogenicity. We enrolled SARS-CoV-2 infection-naïve health care workers who had received two doses of either AdV AZD1222 (n = 184) or mRNA BNT162b2 vaccine (n = 274) between April and October 2021. Blood was collected at least once, 10-48 days after vaccine dose 2 for antibody and B cell analyses. Median ages were 42 and 39 years, for AdV and mRNA vaccinees, respectively. Surrogate virus neutralization test (sVNT) and spike binding antibody titres were a median of 4.2 and 2.2 times lower, respectively, for AdV compared to mRNA vaccinees (p < 0.001). Median percentages of memory B cells that recognized fluorescent-tagged spike and RBD were 2.9 and 8.3 times lower, respectively for AdV compared to mRNA vaccinees. Titres of IgG reactive with human adenovirus type 5 hexon protein rose a median of 2.2-fold after AdV vaccination but were not correlated with anti-spike antibody titres. Together the results show that mRNA induced substantially more sVNT antibody than AdV vaccine, which reflected greater B cell expansion and targeting of the RBD rather than an attenuating effect of anti-vector antibodies. ClinicalTrials.gov Identifier: NCT05110911. |
| Author | Mathew, Suja Jessica Hadiprodjo, A. Khatami, Ameneh Kaiser, Marti Blyth, Christopher C. Hagenauer, Michelle Riley, Kathryn E. Dougherty, Sonia Leung, Vivian Macartney, Kristine Dowson, Leslie Liu, Yi Khvorov, Arseniy Koirala, Archana Wark, Peter Tseng, Yeu Yang Jadhav, Ajay Subbarao, Kanta Fox, Annette Hodgson, David Sánchez-Ovando, Stephany Harvey, Joanne Marshall, Helen Delahunty, Catherine Kucharski, Adam J. Sullivan, Sheena G. Clark, Julia Carolan, Louise Macnish, Marion Cheng, Allen C. |
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Melbourne, Australia – sequence: 5 givenname: Arseniy orcidid: 0000-0002-2423-2848 surname: Khvorov fullname: Khvorov, Arseniy organization: Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia – sequence: 6 givenname: A. surname: Jessica Hadiprodjo fullname: Jessica Hadiprodjo, A. organization: Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia – sequence: 7 givenname: Yeu Yang surname: Tseng fullname: Tseng, Yeu Yang organization: Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia – sequence: 8 givenname: Catherine surname: Delahunty fullname: Delahunty, Catherine organization: Immune Health Program, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, Australia – 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givenname: Archana orcidid: 0000-0002-2567-8825 surname: Koirala fullname: Koirala, Archana organization: The Children’s Hospital at Westmead, Sydney Children’s Hospital Network, National Centre for Immunisation Research and Surveillance, Sydney, Australia – sequence: 24 givenname: Helen orcidid: 0000-0003-2521-5166 surname: Marshall fullname: Marshall, Helen organization: Adelaide Medical School and Robinson Research Institute, The University of Adelaide, Adelaide, Australia – sequence: 25 givenname: Julia orcidid: 0000-0001-7746-0599 surname: Clark fullname: Clark, Julia organization: Queensland Children’s Hospital, Children’s Health Queensland Hospital and Health Service, and University of Queensland, Brisbane, Australia – sequence: 26 givenname: Christopher C. surname: Blyth fullname: Blyth, Christopher C. organization: Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, Perth, Australia – sequence: 27 givenname: Peter surname: Wark fullname: Wark, Peter organization: Immune Health Program, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, Australia – sequence: 28 givenname: Adam J. surname: Kucharski fullname: Kucharski, Adam J. organization: Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK – sequence: 29 givenname: Sheena G. orcidid: 0000-0002-0856-0294 surname: Sullivan fullname: Sullivan, Sheena G. organization: Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia – sequence: 30 givenname: Annette orcidid: 0000-0002-0565-7146 surname: Fox fullname: Fox, Annette email: annette.fox@unimelb.edu.au, annette.fox@influenzacentre.org organization: Department of Infectious Diseases, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/37903679$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_3390_vaccines12091051 crossref_primary_10_3389_fimmu_2025_1487066 crossref_primary_10_1111_bjh_19874 crossref_primary_10_3390_v17010078 crossref_primary_10_3390_vaccines12050493 |
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| ContentType | Journal Article |
| Copyright | 2023 The Author(s) The Author(s) Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved. 2023. The Author(s) |
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| DOI | 10.1016/j.vaccine.2023.10.034 |
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| Keywords | COVID-19 SARS-CoV-2 Antibody Vaccine mRNA B cells Vector |
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| Snippet | •vaccine induced higher Surrogate neutralizing antibody and RBD-targeted B cell responses were greater after mRNA compared to vector vaccine.•Although vector... Highlights•vaccine induced higher Surrogate neutralizing antibody and RBD-targeted B cell responses were greater after mRNA compared to vector vaccine.... •mRNA SARS-CoV-2 vaccine induced higher surrogate neutralizing antibody titres and a more potent, RBD-targeted B cell response than adenoviral... Both vector and mRNA vaccines were an important part of the response to the COVID-19 pandemic and may be required in future outbreaks and pandemics. The aim of... |
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| Title | Superior immunogenicity of mRNA over adenoviral vectored COVID-19 vaccines reflects B cell dynamics independent of anti-vector immunity: Implications for future pandemic vaccines |
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