Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Wei Wang; Sabrina Lusvarghi; Rahul Subramanian; Nusrat J. Epsi; Richard Wang; Emilie Goguet; Anthony C. Fries; Fernando Echegaray; Russell Vassell; Si'Ana A. Coggins; Stephanie A. Richard; David A. Lindholm; Katrin Mende; Evan C. Ewers; Derek T. Larson; Rhonda E. Colombo; Christopher J. Colombo; Janet O. Joseph; Julia S. Rozman; Alfred Smith; Tahaniyat Lalani; Catherine M. Berjohn; Ryan C. Maves; Milissa U. Jones; Rupal Mody; Nikhil Huprikar; Jeffrey Livezey; David Saunders; Monique Hollis-Perry; Gregory Wang; Anuradha Ganesan; Mark P. Simons; Christopher C. Broder; David R. Tribble; Eric D. Laing; Brian K. Agan; Timothy H. Burgess; Edward Mitre; Simon D. Pollett; Leah C. Katzelnick; Carol D. Weiss

doi:10.1016/j.chom.2022.10.012

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

Wei Wang, Sabrina Lusvarghi, Rahul Subramanian, Nusrat J. Epsi, Richard Wang, Emilie Goguet, Anthony C. Fries, Fernando Echegaray, Russell Vassell, Si'Ana A. Coggins, Stephanie A. Richard, David A. Lindholm, Katrin Mende, Evan C. Ewers, Derek T. Larson, Rhonda E. Colombo, Christopher J. Colombo, Janet O. Joseph, Julia S. Rozman, Alfred SmithTahaniyat Lalani, Catherine M. Berjohn, Ryan C. Maves, Milissa U. Jones, Rupal Mody, Nikhil Huprikar, Jeffrey Livezey, David Saunders, Monique Hollis-Perry, Gregory Wang, Anuradha Ganesan, Mark P. Simons, Christopher C. Broder, David R. Tribble, Eric D. Laing, Brian K. Agan, Timothy H. Burgess, Edward Mitre, Simon D. Pollett^*, Leah C. Katzelnick^*, Carol D. Weiss^*

^*Corresponding author for this work

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

3 Scopus citations

Abstract

The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

Original language	English
Pages (from-to)	1745-1758.e7
Journal	Cell Host and Microbe
Volume	30
Issue number	12
DOIs	https://doi.org/10.1016/j.chom.2022.10.012
State	Published - 14 Dec 2022
Externally published	Yes

Keywords

COVID-19 vaccine
Omicron
SARS-CoV-2
SARS-CoV-2 variants
antigenic cartography
antigenic landscape
cartography
hybrid immunity
mRNA vaccine
spike

Access to Document

10.1016/j.chom.2022.10.012

Cite this

Wang, W., Lusvarghi, S., Subramanian, R., Epsi, N. J., Wang, R., Goguet, E., Fries, A. C., Echegaray, F., Vassell, R., Coggins, SA. A., Richard, S. A., Lindholm, D. A., Mende, K., Ewers, E. C., Larson, D. T., Colombo, R. E., Colombo, C. J., Joseph, J. O., Rozman, J. S., ... Weiss, C. D. (2022). Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history. Cell Host and Microbe, 30(12), 1745-1758.e7. https://doi.org/10.1016/j.chom.2022.10.012

@article{d41727d79e2c40db94465dbba5b82421,

title = "Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history",

abstract = "The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.",

keywords = "COVID-19 vaccine, Omicron, SARS-CoV-2, SARS-CoV-2 variants, antigenic cartography, antigenic landscape, cartography, hybrid immunity, mRNA vaccine, spike",

author = "Wei Wang and Sabrina Lusvarghi and Rahul Subramanian and Epsi, {Nusrat J.} and Richard Wang and Emilie Goguet and Fries, {Anthony C.} and Fernando Echegaray and Russell Vassell and Coggins, {Si'Ana A.} and Richard, {Stephanie A.} and Lindholm, {David A.} and Katrin Mende and Ewers, {Evan C.} and Larson, {Derek T.} and Colombo, {Rhonda E.} and Colombo, {Christopher J.} and Joseph, {Janet O.} and Rozman, {Julia S.} and Alfred Smith and Tahaniyat Lalani and Berjohn, {Catherine M.} and Maves, {Ryan C.} and Jones, {Milissa U.} and Rupal Mody and Nikhil Huprikar and Jeffrey Livezey and David Saunders and Monique Hollis-Perry and Gregory Wang and Anuradha Ganesan and Simons, {Mark P.} and Broder, {Christopher C.} and Tribble, {David R.} and Laing, {Eric D.} and Agan, {Brian K.} and Burgess, {Timothy H.} and Edward Mitre and Pollett, {Simon D.} and Katzelnick, {Leah C.} and Weiss, {Carol D.}",

note = "Funding Information: We sincerely thank members of the EPICC COVID-19 Cohort Study Group for their contributions to conducting the study and ensuring effective protocol operations. The authors also acknowledge all who contributed to the EPICC COVID-19 study: The Brooke Army Medical Center: J. Cowden, M. Darling, S. DeLeon, D. Lindholm, A. Markelz, K. Mende, S. Merritt, T. Merritt, N. Turner, and T. Wellington; the Carl R. Darnall Army Medical Center: S. Bazan, D. Hrncir, and P.K Love; the Fort Belvoir Community Hospital: N. Dimascio-Johnson, E. Ewers, K. Gallagher, C. Glinn, U. Jarral, D Jennings, D. Larson, A. Mentzos, K Reterstoff, A. Rutt, A. Silva, and C. West; the Henry M. Jackson Foundation: P. Blair, J. Chenoweth, and D. Clark; the Madigan Army Medical Center: J. Bowman, S. Chambers, C. Colombo, R. Colombo, C. Conlon, K. Everson, P. Faestel, T. Ferguson, L. Gordon, S. Grogan, S. Lis; M. Martin, C. Mount, D. Musfeldt, D. Odineal, M. Perreault, W. Robb-McGrath, R. Sainato, C. Schofield, C. Skinner, M. Stein, M. Switzer, M. Timlin, and J S. Wood; the Naval Medical Center Portsmouth: S. Banks, R. Carpenter, L. Kim, K. Kronmann, T. Lalani, T. Lee, A. Smith, R. Smith, R. Tant, and T. Warkentien; the Naval Medical Center San Diego: C. Berjohn, S. Cammarata, N. Kirkland, D. Libraty, R. Maves, and G. Utz; the Tripler Army Medical Center: C. Bradley, S. Chi, R. Flanagan, A. Fuentes, M. Jones, N. Leslie, C. Lucas, C. Madar, K. Miyasato, and C. Uyehara; the Uniformed Services University of the Health Sciences: H. Adams, B. Agan, L. Andronescu, A. Austin, C. Broder, T. Burgess, C. Byrne, K Chung, J. Davies, C. English, N. Epsi, C. Fox, M. Fritschlanski, M. Grother, A. Hadley, P. Hickey, E. Laing, C. Lanteri, J. Livezey, A. Malloy, R. Mohammed, C. Morales, L. Nevo, P. Nwachukwu, C. Olsen, E. Parmelee, S. Pollett, S. Richard, J. Rozman, J. Rusiecki, E. Samuels, M. Sanchez, A. Scher, M. Simons, A. Snow, K. Telu, D. Tribble, M. Tso, L. Ulomi, and M. Wayman; the U.S. Air Force School of Aerospace Medicine: TSgt T. Chao, R. Chapleau, M. Christian, A. Fries, C. Harrington, V. Hogan, S. Huntsberger, K. Lanter, E. Macias, J. Meyer, S. Purves, K. Reynolds, J. Rodriguez, and C. Starr; the U.S. Army Medical Research Institute of Infectious Diseases: J Kugelman; U.S. Coast Guard: J. Iskander and I. Kamara; the Womack Army Medical Center: B. Barton, D. Hostler, J. Hostler, K. Lago, C. Maldonado, and J. Mehrer, the William Beaumont Army Medical Center: T. Hunter, J. Mejia, R. Mody, J. Montes, R. Resendez, and P. Sandoval; the Walter Reed National Military Medical Center: I. Barahona, A. Baya, A. Ganesan, N. Huprikar, and B. Johnson; and the Walter Reed Army Institute of Research: S. Peel. The authors wish to also acknowledge the following individuals for their contributions to the PASS (IDCRP-126) COVID-19 study. The Henry M. Jackson Foundation: Alyssa Lindrose, Matthew Moser, Emily C. Samuels, Belinda Jackson-Thompson, Julian Davies, Luca Illinik, Mimi Sanchez, Orlando Ortega, and Edward Parmelee. NMRC-CTC (Naval Medical Research Center-Clinical Trials Center): Santina E. Maiolatesi. Christopher A. Duplessis. NMRC-CTC/General Dynamics. Kathleen F. Ramsey, Anatalio E. Reyes, Yolanda Alcorta, and Mimi A. Wong. We also thank the HVTN and CoVPN for use of samples from the CoVPN trial. Financial support: This work was supported by institutional research funds from the U.S. Food and Drug Administration (FDA), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), and awards from NIAID/NIH through an interagency agreement (AAI21013-001-00000) with Center for Biologics Evaluation and Research, FDA, as part of the U.S. Government COVID-19 response efforts, and the Defense Health Program (HU00012020067, HU00012020094, HU00012120104) and the NIAID (HU00011920111). The protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USU) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded in part by NIAID under an interagency agreement (Y1-AI-5072). R.S. was supported by an appointment to the NIAID Emerging Leaders in Data Science Research Participation Program. This work also used samples funded in part with federal funds from the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness, and the Response, Biomedical Advanced Research & Development Authority. Disclaimers: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences (USU); the Department of Defense (DoD); the Departments of the Army, Navy, or Air Force; the Defense Health Agency, or the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. The mention of trade names, commercial products, or organizations does not imply an endorsement by the U.S. Government. The investigators have adhered to the policies for the protection of human subjects as prescribed in 45 CFR 46. The Emerging Leaders in Data Science Research Participation Program is administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and NIAID. ORISE is managed by Oak Ridge Associated Universities (ORAU) under DOE contract number DE-SC0014664. All opinions expressed in this paper are the author's and do not necessarily reflect the policies and views of the FDA, NIAID, DOE, or ORAU/ORISE. W.W. S.L. A.C.F. R.V. D.A.L. E.C.E, D.T.L. A.S. C.M.B. M.U.J. R.M. N.H. J.L. D.S. M.H.-P. M.P.S. C.C.B. D.R.T. E.D.L. E.M. L.C.K. and C.D.W. are service members or employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the U.S. Government.” Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties. W.W. S.L. L.C.K. C.D.W. and S.D.P. conceived and designed the study and experiments. W.W. S.L. C.D.W. A.C.F. R.W. E.D.L. E.G. R.V. S.A.C. M.P.S. D.R.T. T.H.B. B.K.A. E.M. and S.D.P. acquired the data and performed the experiments. W.W. L.C.K. C.D.W. S.L. R.S. N.J.E. A.C.F. F.E. J.O.J. and S.A.R. created the detailed analysis plan and/or analyzed the data. W.W. L.C.K. C.D.W. S.L. R.S. A.C.F. S.D.P. E.M. E.D.L. and C.M.B. interpreted the findings. E.G. J.S.R. D.A.L. K.M. E.C.E. D.T.L. R.E.C. C.J.C. A.S. T.L. C.M.B. R.C.M. M.U.J. R.M. N.H. J.L. D.S. M.H.-P. G.W. A.G. M.P.S. and C.D.W. contributed resources, reagents, materials, and specimens. W.W. L.C.K. C.D.W. S.L. R.S. and S.D.P. composed the first draft of the manuscript. W.W. L.C.K. C.D.W. S.L. R.S. N.J.E. A.C.F. E.L. and E.M. provided critical revisions and edits (scientific content) to provisional drafts. All the authors reviewed and approved the final version for submission. S.D.P. T.H.B, D.R.T. J.S.R. and M.P.S. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the U.S. Government COVID-19 response. Neither is related to the work presented here. Funding Information: We sincerely thank members of the EPICC COVID-19 Cohort Study Group for their contributions to conducting the study and ensuring effective protocol operations. The authors also acknowledge all who contributed to the EPICC COVID-19 study: The Brooke Army Medical Center : J. Cowden, M. Darling, S. DeLeon, D. Lindholm, A. Markelz, K. Mende, S. Merritt, T. Merritt, N. Turner, and T. Wellington; the Carl R. Darnall Army Medical Center : S. Bazan, D. Hrncir, and P.K Love; the Fort Belvoir Community Hospital : N. Dimascio-Johnson, E. Ewers, K. Gallagher, C. Glinn, U. Jarral, D Jennings, D. Larson, A. Mentzos, K Reterstoff, A. Rutt, A. Silva, and C. West; the Henry M. Jackson Foundation : P. Blair, J. Chenoweth, and D. Clark; the Madigan Army Medical Center : J. Bowman, S. Chambers, C. Colombo, R. Colombo, C. Conlon, K. Everson, P. Faestel, T. Ferguson, L. Gordon, S. Grogan, S. Lis; M. Martin, C. Mount, D. Musfeldt, D. Odineal, M. Perreault, W. Robb-McGrath, R. Sainato, C. Schofield, C. Skinner, M. Stein, M. Switzer, M. Timlin, and J S. Wood; the Naval Medical Center Portsmouth: S. Banks, R. Carpenter, L. Kim, K. Kronmann, T. Lalani, T. Lee, A. Smith, R. Smith, R. Tant, and T. Warkentien; the Naval Medical Center San Diego : C. Berjohn, S. Cammarata, N. Kirkland, D. Libraty, R. Maves, and G. Utz; the Tripler Army Medical Center : C. Bradley, S. Chi, R. Flanagan, A. Fuentes, M. Jones, N. Leslie, C. Lucas, C. Madar, K. Miyasato, and C. Uyehara; the Uniformed Services University of the Health Sciences : H. Adams, B. Agan, L. Andronescu, A. Austin, C. Broder, T. Burgess, C. Byrne, K Chung, J. Davies, C. English, N. Epsi, C. Fox, M. Fritschlanski, M. Grother, A. Hadley, P. Hickey, E. Laing, C. Lanteri, J. Livezey, A. Malloy, R. Mohammed, C. Morales, L. Nevo, P. Nwachukwu, C. Olsen, E. Parmelee, S. Pollett, S. Richard, J. Rozman, J. Rusiecki, E. Samuels, M. Sanchez, A. Scher, M. Simons, A. Snow, K. Telu, D. Tribble, M. Tso, L. Ulomi, and M. Wayman; the U.S. Air Force School of Aerospace Medicine : TSgt T. Chao, R. Chapleau, M. Christian, A. Fries, C. Harrington, V. Hogan, S. Huntsberger, K. Lanter, E. Macias, J. Meyer, S. Purves, K. Reynolds, J. Rodriguez, and C. Starr; the U.S. Army Medical Research Institute of Infectious Diseases : J Kugelman; U.S. Coast Guard: J. Iskander and I. Kamara; the Womack Army Medical Center : B. Barton, D. Hostler, J. Hostler, K. Lago, C. Maldonado, and J. Mehrer, the William Beaumont Army Medical Center : T. Hunter, J. Mejia, R. Mody, J. Montes, R. Resendez, and P. Sandoval; the Walter Reed National Military Medical Center : I. Barahona, A. Baya, A. Ganesan, N. Huprikar, and B. Johnson; and the Walter Reed Army Institute of Research : S. Peel. The authors wish to also acknowledge the following individuals for their contributions to the PASS (IDCRP-126) COVID-19 study. The Henry M. Jackson Foundation : Alyssa Lindrose, Matthew Moser, Emily C. Samuels, Belinda Jackson-Thompson, Julian Davies, Luca Illinik, Mimi Sanchez, Orlando Ortega, and Edward Parmelee. NMRC-CTC (Naval Medical Research Center-Clinical Trials Center): Santina E. Maiolatesi. Christopher A. Duplessis. NMRC-CTC/General Dynamics. Kathleen F. Ramsey, Anatalio E. Reyes, Yolanda Alcorta, and Mimi A. Wong. We also thank the HVTN and CoVPN for use of samples from the CoVPN trial. Financial support: This work was supported by institutional research funds from the U.S. Food and Drug Administration (FDA), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), and awards from NIAID/NIH through an interagency agreement ( AAI21013-001-00000 ) with Center for Biologics Evaluation and Research , FDA , as part of the U.S. Government COVID-19 response efforts, and the Defense Health Program ( HU00012020067 , HU00012020094 , HU00012120104 ) and the NIAID ( HU00011920111 ). The protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USU) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded in part by NIAID under an interagency agreement (Y1-AI-5072). R.S. was supported by an appointment to the NIAID Emerging Leaders in Data Science Research Participation Program . This work also used samples funded in part with federal funds from the U.S. Department of Health and Human Services , Office of the Assistant Secretary for Preparedness , and the Response, Biomedical Advanced Research & Development Authority . Funding Information: Disclaimers: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences (USU); the Department of Defense (DoD); the Departments of the Army, Navy, or Air Force; the Defense Health Agency, or the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. The mention of trade names, commercial products, or organizations does not imply an endorsement by the U.S. Government. The investigators have adhered to the policies for the protection of human subjects as prescribed in 45 CFR 46. The Emerging Leaders in Data Science Research Participation Program is administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and NIAID. ORISE is managed by Oak Ridge Associated Universities (ORAU) under DOE contract number DE-SC0014664 . All opinions expressed in this paper are the author{\textquoteright}s and do not necessarily reflect the policies and views of the FDA, NIAID, DOE, or ORAU/ORISE. Funding Information: S.D.P., T.H.B, D.R.T., J.S.R., and M.P.S. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the U.S. Government COVID-19 response. Neither is related to the work presented here. Publisher Copyright: {\textcopyright} 2022",

year = "2022",

month = dec,

day = "14",

doi = "10.1016/j.chom.2022.10.012",

language = "English",

volume = "30",

pages = "1745--1758.e7",

journal = "Cell Host and Microbe",

issn = "1931-3128",

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}

Wang, W, Lusvarghi, S, Subramanian, R, Epsi, NJ, Wang, R, Goguet, E, Fries, AC, Echegaray, F, Vassell, R, Coggins, SAA, Richard, SA , Lindholm, DA , Mende, K, Ewers, EC, Larson, DT, Colombo, RE , Colombo, CJ, Joseph, JO, Rozman, JS, Smith, A, Lalani, T , Berjohn, CM, Maves, RC, Jones, MU, Mody, R, Huprikar, N, Livezey, J, Saunders, D, Hollis-Perry, M, Wang, G, Ganesan, A , Simons, MP, Broder, CC, Tribble, DR, Laing, ED, Agan, BK, Burgess, TH, Mitre, E, Pollett, SD, Katzelnick, LC & Weiss, CD 2022, 'Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history', Cell Host and Microbe, vol. 30, no. 12, pp. 1745-1758.e7. https://doi.org/10.1016/j.chom.2022.10.012

TY - JOUR

T1 - Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

AU - Wang, Wei

AU - Lusvarghi, Sabrina

AU - Subramanian, Rahul

AU - Epsi, Nusrat J.

AU - Wang, Richard

AU - Goguet, Emilie

AU - Fries, Anthony C.

AU - Echegaray, Fernando

AU - Vassell, Russell

AU - Coggins, Si'Ana A.

AU - Richard, Stephanie A.

AU - Lindholm, David A.

AU - Mende, Katrin

AU - Ewers, Evan C.

AU - Larson, Derek T.

AU - Colombo, Rhonda E.

AU - Colombo, Christopher J.

AU - Joseph, Janet O.

AU - Rozman, Julia S.

AU - Smith, Alfred

AU - Lalani, Tahaniyat

AU - Berjohn, Catherine M.

AU - Maves, Ryan C.

AU - Jones, Milissa U.

AU - Mody, Rupal

AU - Huprikar, Nikhil

AU - Livezey, Jeffrey

AU - Saunders, David

AU - Hollis-Perry, Monique

AU - Wang, Gregory

AU - Ganesan, Anuradha

AU - Simons, Mark P.

AU - Broder, Christopher C.

AU - Tribble, David R.

AU - Laing, Eric D.

AU - Agan, Brian K.

AU - Burgess, Timothy H.

AU - Mitre, Edward

AU - Pollett, Simon D.

AU - Katzelnick, Leah C.

AU - Weiss, Carol D.

N1 - Funding Information: We sincerely thank members of the EPICC COVID-19 Cohort Study Group for their contributions to conducting the study and ensuring effective protocol operations. The authors also acknowledge all who contributed to the EPICC COVID-19 study: The Brooke Army Medical Center: J. Cowden, M. Darling, S. DeLeon, D. Lindholm, A. Markelz, K. Mende, S. Merritt, T. Merritt, N. Turner, and T. Wellington; the Carl R. Darnall Army Medical Center: S. Bazan, D. Hrncir, and P.K Love; the Fort Belvoir Community Hospital: N. Dimascio-Johnson, E. Ewers, K. Gallagher, C. Glinn, U. Jarral, D Jennings, D. Larson, A. Mentzos, K Reterstoff, A. Rutt, A. Silva, and C. West; the Henry M. Jackson Foundation: P. Blair, J. Chenoweth, and D. Clark; the Madigan Army Medical Center: J. Bowman, S. Chambers, C. Colombo, R. Colombo, C. Conlon, K. Everson, P. Faestel, T. Ferguson, L. Gordon, S. Grogan, S. Lis; M. Martin, C. Mount, D. Musfeldt, D. Odineal, M. Perreault, W. Robb-McGrath, R. Sainato, C. Schofield, C. Skinner, M. Stein, M. Switzer, M. Timlin, and J S. Wood; the Naval Medical Center Portsmouth: S. Banks, R. Carpenter, L. Kim, K. Kronmann, T. Lalani, T. Lee, A. Smith, R. Smith, R. Tant, and T. Warkentien; the Naval Medical Center San Diego: C. Berjohn, S. Cammarata, N. Kirkland, D. Libraty, R. Maves, and G. Utz; the Tripler Army Medical Center: C. Bradley, S. Chi, R. Flanagan, A. Fuentes, M. Jones, N. Leslie, C. Lucas, C. Madar, K. Miyasato, and C. Uyehara; the Uniformed Services University of the Health Sciences: H. Adams, B. Agan, L. Andronescu, A. Austin, C. Broder, T. Burgess, C. Byrne, K Chung, J. Davies, C. English, N. Epsi, C. Fox, M. Fritschlanski, M. Grother, A. Hadley, P. Hickey, E. Laing, C. Lanteri, J. Livezey, A. Malloy, R. Mohammed, C. Morales, L. Nevo, P. Nwachukwu, C. Olsen, E. Parmelee, S. Pollett, S. Richard, J. Rozman, J. Rusiecki, E. Samuels, M. Sanchez, A. Scher, M. Simons, A. Snow, K. Telu, D. Tribble, M. Tso, L. Ulomi, and M. Wayman; the U.S. Air Force School of Aerospace Medicine: TSgt T. Chao, R. Chapleau, M. Christian, A. Fries, C. Harrington, V. Hogan, S. Huntsberger, K. Lanter, E. Macias, J. Meyer, S. Purves, K. Reynolds, J. Rodriguez, and C. Starr; the U.S. Army Medical Research Institute of Infectious Diseases: J Kugelman; U.S. Coast Guard: J. Iskander and I. Kamara; the Womack Army Medical Center: B. Barton, D. Hostler, J. Hostler, K. Lago, C. Maldonado, and J. Mehrer, the William Beaumont Army Medical Center: T. Hunter, J. Mejia, R. Mody, J. Montes, R. Resendez, and P. Sandoval; the Walter Reed National Military Medical Center: I. Barahona, A. Baya, A. Ganesan, N. Huprikar, and B. Johnson; and the Walter Reed Army Institute of Research: S. Peel. The authors wish to also acknowledge the following individuals for their contributions to the PASS (IDCRP-126) COVID-19 study. The Henry M. Jackson Foundation: Alyssa Lindrose, Matthew Moser, Emily C. Samuels, Belinda Jackson-Thompson, Julian Davies, Luca Illinik, Mimi Sanchez, Orlando Ortega, and Edward Parmelee. NMRC-CTC (Naval Medical Research Center-Clinical Trials Center): Santina E. Maiolatesi. Christopher A. Duplessis. NMRC-CTC/General Dynamics. Kathleen F. Ramsey, Anatalio E. Reyes, Yolanda Alcorta, and Mimi A. Wong. We also thank the HVTN and CoVPN for use of samples from the CoVPN trial. Financial support: This work was supported by institutional research funds from the U.S. Food and Drug Administration (FDA), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), and awards from NIAID/NIH through an interagency agreement (AAI21013-001-00000) with Center for Biologics Evaluation and Research, FDA, as part of the U.S. Government COVID-19 response efforts, and the Defense Health Program (HU00012020067, HU00012020094, HU00012120104) and the NIAID (HU00011920111). The protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USU) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded in part by NIAID under an interagency agreement (Y1-AI-5072). R.S. was supported by an appointment to the NIAID Emerging Leaders in Data Science Research Participation Program. This work also used samples funded in part with federal funds from the U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness, and the Response, Biomedical Advanced Research & Development Authority. Disclaimers: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences (USU); the Department of Defense (DoD); the Departments of the Army, Navy, or Air Force; the Defense Health Agency, or the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. The mention of trade names, commercial products, or organizations does not imply an endorsement by the U.S. Government. The investigators have adhered to the policies for the protection of human subjects as prescribed in 45 CFR 46. The Emerging Leaders in Data Science Research Participation Program is administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and NIAID. ORISE is managed by Oak Ridge Associated Universities (ORAU) under DOE contract number DE-SC0014664. All opinions expressed in this paper are the author's and do not necessarily reflect the policies and views of the FDA, NIAID, DOE, or ORAU/ORISE. W.W. S.L. A.C.F. R.V. D.A.L. E.C.E, D.T.L. A.S. C.M.B. M.U.J. R.M. N.H. J.L. D.S. M.H.-P. M.P.S. C.C.B. D.R.T. E.D.L. E.M. L.C.K. and C.D.W. are service members or employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that “Copyright protection under this title is not available for any work of the U.S. Government.” Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties. W.W. S.L. L.C.K. C.D.W. and S.D.P. conceived and designed the study and experiments. W.W. S.L. C.D.W. A.C.F. R.W. E.D.L. E.G. R.V. S.A.C. M.P.S. D.R.T. T.H.B. B.K.A. E.M. and S.D.P. acquired the data and performed the experiments. W.W. L.C.K. C.D.W. S.L. R.S. N.J.E. A.C.F. F.E. J.O.J. and S.A.R. created the detailed analysis plan and/or analyzed the data. W.W. L.C.K. C.D.W. S.L. R.S. A.C.F. S.D.P. E.M. E.D.L. and C.M.B. interpreted the findings. E.G. J.S.R. D.A.L. K.M. E.C.E. D.T.L. R.E.C. C.J.C. A.S. T.L. C.M.B. R.C.M. M.U.J. R.M. N.H. J.L. D.S. M.H.-P. G.W. A.G. M.P.S. and C.D.W. contributed resources, reagents, materials, and specimens. W.W. L.C.K. C.D.W. S.L. R.S. and S.D.P. composed the first draft of the manuscript. W.W. L.C.K. C.D.W. S.L. R.S. N.J.E. A.C.F. E.L. and E.M. provided critical revisions and edits (scientific content) to provisional drafts. All the authors reviewed and approved the final version for submission. S.D.P. T.H.B, D.R.T. J.S.R. and M.P.S. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the U.S. Government COVID-19 response. Neither is related to the work presented here. Funding Information: We sincerely thank members of the EPICC COVID-19 Cohort Study Group for their contributions to conducting the study and ensuring effective protocol operations. The authors also acknowledge all who contributed to the EPICC COVID-19 study: The Brooke Army Medical Center : J. Cowden, M. Darling, S. DeLeon, D. Lindholm, A. Markelz, K. Mende, S. Merritt, T. Merritt, N. Turner, and T. Wellington; the Carl R. Darnall Army Medical Center : S. Bazan, D. Hrncir, and P.K Love; the Fort Belvoir Community Hospital : N. Dimascio-Johnson, E. Ewers, K. Gallagher, C. Glinn, U. Jarral, D Jennings, D. Larson, A. Mentzos, K Reterstoff, A. Rutt, A. Silva, and C. West; the Henry M. Jackson Foundation : P. Blair, J. Chenoweth, and D. Clark; the Madigan Army Medical Center : J. Bowman, S. Chambers, C. Colombo, R. Colombo, C. Conlon, K. Everson, P. Faestel, T. Ferguson, L. Gordon, S. Grogan, S. Lis; M. Martin, C. Mount, D. Musfeldt, D. Odineal, M. Perreault, W. Robb-McGrath, R. Sainato, C. Schofield, C. Skinner, M. Stein, M. Switzer, M. Timlin, and J S. Wood; the Naval Medical Center Portsmouth: S. Banks, R. Carpenter, L. Kim, K. Kronmann, T. Lalani, T. Lee, A. Smith, R. Smith, R. Tant, and T. Warkentien; the Naval Medical Center San Diego : C. Berjohn, S. Cammarata, N. Kirkland, D. Libraty, R. Maves, and G. Utz; the Tripler Army Medical Center : C. Bradley, S. Chi, R. Flanagan, A. Fuentes, M. Jones, N. Leslie, C. Lucas, C. Madar, K. Miyasato, and C. Uyehara; the Uniformed Services University of the Health Sciences : H. Adams, B. Agan, L. Andronescu, A. Austin, C. Broder, T. Burgess, C. Byrne, K Chung, J. Davies, C. English, N. Epsi, C. Fox, M. Fritschlanski, M. Grother, A. Hadley, P. Hickey, E. Laing, C. Lanteri, J. Livezey, A. Malloy, R. Mohammed, C. Morales, L. Nevo, P. Nwachukwu, C. Olsen, E. Parmelee, S. Pollett, S. Richard, J. Rozman, J. Rusiecki, E. Samuels, M. Sanchez, A. Scher, M. Simons, A. Snow, K. Telu, D. Tribble, M. Tso, L. Ulomi, and M. Wayman; the U.S. Air Force School of Aerospace Medicine : TSgt T. Chao, R. Chapleau, M. Christian, A. Fries, C. Harrington, V. Hogan, S. Huntsberger, K. Lanter, E. Macias, J. Meyer, S. Purves, K. Reynolds, J. Rodriguez, and C. Starr; the U.S. Army Medical Research Institute of Infectious Diseases : J Kugelman; U.S. Coast Guard: J. Iskander and I. Kamara; the Womack Army Medical Center : B. Barton, D. Hostler, J. Hostler, K. Lago, C. Maldonado, and J. Mehrer, the William Beaumont Army Medical Center : T. Hunter, J. Mejia, R. Mody, J. Montes, R. Resendez, and P. Sandoval; the Walter Reed National Military Medical Center : I. Barahona, A. Baya, A. Ganesan, N. Huprikar, and B. Johnson; and the Walter Reed Army Institute of Research : S. Peel. The authors wish to also acknowledge the following individuals for their contributions to the PASS (IDCRP-126) COVID-19 study. The Henry M. Jackson Foundation : Alyssa Lindrose, Matthew Moser, Emily C. Samuels, Belinda Jackson-Thompson, Julian Davies, Luca Illinik, Mimi Sanchez, Orlando Ortega, and Edward Parmelee. NMRC-CTC (Naval Medical Research Center-Clinical Trials Center): Santina E. Maiolatesi. Christopher A. Duplessis. NMRC-CTC/General Dynamics. Kathleen F. Ramsey, Anatalio E. Reyes, Yolanda Alcorta, and Mimi A. Wong. We also thank the HVTN and CoVPN for use of samples from the CoVPN trial. Financial support: This work was supported by institutional research funds from the U.S. Food and Drug Administration (FDA), the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH), and awards from NIAID/NIH through an interagency agreement ( AAI21013-001-00000 ) with Center for Biologics Evaluation and Research , FDA , as part of the U.S. Government COVID-19 response efforts, and the Defense Health Program ( HU00012020067 , HU00012020094 , HU00012120104 ) and the NIAID ( HU00011920111 ). The protocol was executed by the Infectious Disease Clinical Research Program (IDCRP), a Department of Defense (DoD) program executed by the Uniformed Services University of the Health Sciences (USU) through a cooperative agreement by the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc. (HJF). This project has been funded in part by NIAID under an interagency agreement (Y1-AI-5072). R.S. was supported by an appointment to the NIAID Emerging Leaders in Data Science Research Participation Program . This work also used samples funded in part with federal funds from the U.S. Department of Health and Human Services , Office of the Assistant Secretary for Preparedness , and the Response, Biomedical Advanced Research & Development Authority . Funding Information: Disclaimers: The contents of this publication are the sole responsibility of the author(s) and do not necessarily reflect the views, opinions, or policies of Uniformed Services University of the Health Sciences (USU); the Department of Defense (DoD); the Departments of the Army, Navy, or Air Force; the Defense Health Agency, or the Henry M. Jackson Foundation for the Advancement of Military Medicine Inc. The mention of trade names, commercial products, or organizations does not imply an endorsement by the U.S. Government. The investigators have adhered to the policies for the protection of human subjects as prescribed in 45 CFR 46. The Emerging Leaders in Data Science Research Participation Program is administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy (DOE) and NIAID. ORISE is managed by Oak Ridge Associated Universities (ORAU) under DOE contract number DE-SC0014664 . All opinions expressed in this paper are the author’s and do not necessarily reflect the policies and views of the FDA, NIAID, DOE, or ORAU/ORISE. Funding Information: S.D.P., T.H.B, D.R.T., J.S.R., and M.P.S. report that the Uniformed Services University (USU) Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and the Henry M. Jackson Foundation (HJF) were funded under a Cooperative Research and Development Agreement to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase III vaccine trial sponsored by AstraZeneca. Both trials were part of the U.S. Government COVID-19 response. Neither is related to the work presented here. Publisher Copyright: © 2022

PY - 2022/12/14

Y1 - 2022/12/14

N2 - The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

AB - The rapid emergence of SARS-CoV-2 variants challenges vaccination strategies. Here, we collected 201 serum samples from persons with a single infection or multiple vaccine exposures, or both. We measured their neutralization titers against 15 natural variants and 7 variants with engineered spike mutations and analyzed antigenic diversity. Antigenic maps of primary infection sera showed that Omicron sublineages BA.2, BA.4/BA.5, and BA.2.12.1 are distinct from BA.1 and more similar to Beta/Gamma/Mu variants. Three mRNA COVID-19 vaccinations increased neutralization of BA.1 more than BA.4/BA.5 or BA.2.12.1. BA.1 post-vaccination infection elicited higher neutralization titers to all variants than three vaccinations alone, although with less neutralization to BA.2.12.1 and BA.4/BA.5. Those with BA.1 infection after two or three vaccinations had similar neutralization titer magnitude and antigenic recognition. Accounting for antigenic differences among variants when interpreting neutralization titers can aid the understanding of complex patterns in humoral immunity that informs the selection of future COVID-19 vaccine strains.

KW - COVID-19 vaccine

KW - Omicron

KW - SARS-CoV-2

KW - SARS-CoV-2 variants

KW - antigenic cartography

KW - antigenic landscape

KW - cartography

KW - hybrid immunity

KW - mRNA vaccine

KW - spike

UR - http://www.scopus.com/inward/record.url?scp=85141496873&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2022.10.012

DO - 10.1016/j.chom.2022.10.012

M3 - Article

C2 - 36356586

AN - SCOPUS:85141496873

SN - 1931-3128

VL - 30

SP - 1745-1758.e7

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 12

ER -

Antigenic cartography of well-characterized human sera shows SARS-CoV-2 neutralization differences based on infection and vaccination history

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