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Vaccine breakthrough infection leads to distinct profiles of neutralizing antibody responses by SARS-CoV-2 variant
Michael S. Seaman, Mark J. Siedner, Julie Boucau, Christy L. Lavine, Fadi Ghantous, May Y. Liew, Josh I. Mathews, Arshdeep Singh, Caitlin Marino, James Regan, Rockib Uddin, Manish C. Choudhary, James P. Flynn, Geoffrey Chen, Ashley M. Stuckwisch, Taryn Lipiner, Autumn Kittilson, Meghan Melberg, Rebecca F. Gilbert, Zahra Reynolds, Surabhi L. Iyer, Grace C. Chamberlin, Tammy D. Vyas, Jatin M. Vyas, Marcia B. Goldberg, Jeremy Luban, Jonathan Z. Li, Amy K. Barczak, Jacob E. Lemieux
Michael S. Seaman, Mark J. Siedner, Julie Boucau, Christy L. Lavine, Fadi Ghantous, May Y. Liew, Josh I. Mathews, Arshdeep Singh, Caitlin Marino, James Regan, Rockib Uddin, Manish C. Choudhary, James P. Flynn, Geoffrey Chen, Ashley M. Stuckwisch, Taryn Lipiner, Autumn Kittilson, Meghan Melberg, Rebecca F. Gilbert, Zahra Reynolds, Surabhi L. Iyer, Grace C. Chamberlin, Tammy D. Vyas, Jatin M. Vyas, Marcia B. Goldberg, Jeremy Luban, Jonathan Z. Li, Amy K. Barczak, Jacob E. Lemieux
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Research Article COVID-19

Vaccine breakthrough infection leads to distinct profiles of neutralizing antibody responses by SARS-CoV-2 variant

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Abstract

Protective immunity against SARS-CoV-2 infection after COVID-19 vaccination may differ by variant. We enrolled vaccinated (n = 39) and unvaccinated (n = 11) individuals with acute, symptomatic SARS-CoV-2 Delta or Omicron infection and performed SARS-CoV-2 viral load quantification, whole-genome sequencing, and variant-specific antibody characterization at the time of acute illness and convalescence. Viral load at the time of infection was inversely correlated with antibody binding and neutralizing antibody responses. Across all variants tested, convalescent neutralization titers in unvaccinated individuals were markedly lower than in vaccinated individuals. Increases in antibody titers and neutralizing activity occurred at convalescence in a variant-specific manner. For example, among individuals infected with the Delta variant, neutralizing antibody responses were weakest against BA.2, whereas infection with Omicron BA.1 variant generated a broader response against all tested variants, including BA.2.

Authors

Michael S. Seaman, Mark J. Siedner, Julie Boucau, Christy L. Lavine, Fadi Ghantous, May Y. Liew, Josh I. Mathews, Arshdeep Singh, Caitlin Marino, James Regan, Rockib Uddin, Manish C. Choudhary, James P. Flynn, Geoffrey Chen, Ashley M. Stuckwisch, Taryn Lipiner, Autumn Kittilson, Meghan Melberg, Rebecca F. Gilbert, Zahra Reynolds, Surabhi L. Iyer, Grace C. Chamberlin, Tammy D. Vyas, Jatin M. Vyas, Marcia B. Goldberg, Jeremy Luban, Jonathan Z. Li, Amy K. Barczak, Jacob E. Lemieux

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Figure 2

Neutralizing antibody responses, as measured by NT50, against a panel of pseudoviruses.

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Neutralizing antibody responses, as measured by NT50, against a panel of...
The geometric mean is shown with a bar. Patients infected with Delta variants are shown in the top panel. Patients infected with the Omicron (BA.1) variant are shown in the bottom panel. Significance test of medians (Kruskal-Wallis) is shown. **P < 0.01. The solid bars show geometric mean for each group. Vaccination status is denoted by point shape. Subjects with seronegativity to Nucleocapsid (N) antigens at baseline are colored red; those with N seropositivity are colored blue.

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