SARS-CoV-2–specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge
Bezawit A. Woldemeskel, Caroline C. Garliss, Tihitina Y. Aytenfisu, Trevor S. Johnston, Evan J. Beck, Arbor G. Dykema, Nicole Frumento, Desiree A. Wright, Andrew H. Yang, Alexander I. Damanakis, Oliver Laeyendecker, Andrea L. Cox, Heba H. Mostafa, Andrew H. Karaba, Joel N. Blankson
Bezawit A. Woldemeskel, Caroline C. Garliss, Tihitina Y. Aytenfisu, Trevor S. Johnston, Evan J. Beck, Arbor G. Dykema, Nicole Frumento, Desiree A. Wright, Andrew H. Yang, Alexander I. Damanakis, Oliver Laeyendecker, Andrea L. Cox, Heba H. Mostafa, Andrew H. Karaba, Joel N. Blankson
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Clinical Research and Public Health COVID-19

SARS-CoV-2–specific immune responses in boosted vaccine recipients with breakthrough infections during the Omicron variant surge

Abstract

Background Breakthrough SARS-CoV-2 infections in vaccinated individuals have been previously associated with suboptimal humoral immunity. However, less is known about breakthrough infections with the Omicron variant.Methods We analyzed SARS-CoV-2–specific antibody and cellular responses in healthy vaccine recipients who experienced breakthrough infections a median of 50 days after receiving a booster mRNA vaccine with an ACE2 binding inhibition assay and an ELISpot assay, respectively.Results We found that high levels of antibodies inhibited vaccine strain spike protein binding to ACE2 but that lower levels inhibited Omicron variant spike protein binding to ACE2 in 4 boosted vaccine recipients prior to infection. The levels of antibodies that inhibited vaccine strain and Omicron spike protein binding after breakthrough in 18 boosted vaccine recipients were similar to levels seen in COVID-19–negative boosted vaccine recipients. In contrast, boosted vaccine recipients had significantly stronger T cell responses to both vaccine strain and Omicron variant spike proteins at the time of breakthrough.Conclusion Our data suggest that breakthrough infections with the Omicron variant can occur despite robust immune responses to the vaccine strain spike protein.Funding This work was supported by the Johns Hopkins COVID-19 Vaccine-related Research Fund and by funds from the National Institute of Allergy and Infectious Disease intramural program as well as awards from the National Cancer Institute (U54CA260492) and the National Institutes of Allergy and Infectious Disease (K08AI156021 and U01AI138897).

Authors

Bezawit A. Woldemeskel, Caroline C. Garliss, Tihitina Y. Aytenfisu, Trevor S. Johnston, Evan J. Beck, Arbor G. Dykema, Nicole Frumento, Desiree A. Wright, Andrew H. Yang, Alexander I. Damanakis, Oliver Laeyendecker, Andrea L. Cox, Heba H. Mostafa, Andrew H. Karaba, Joel N. Blankson

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Figure 2

Characterization of antibody levels in boosted vaccine recipients with breakthrough infections.

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Characterization of antibody levels in boosted vaccine recipients with b...
(A) Spike-binding antibodies found in fully vaccinated individuals prior to their booster shots (Pre-boost VRs), individuals 1–3 weeks (Post-boost VRs 1–3 weeks) or 1–3 months (Post-boost 1–3 months) after their booster shot, breakthrough VRs 1–3 weeks after symptom onset, and VR21, VR26, VR37 and VR97 1–3 weeks after their booster shots and before they experienced breakthrough infections. The orange diamonds represent VR21, VR26, VR37, and VR97 at the breakthrough time point. The orange triangles represent participants who received the Ad26.COV2 vaccine followed by the mRNA1273 booster vaccine. (B) Receptor binding domain (RBD) antibodies in preboost, postboost, and breakthrough VRs as well as VR21, VR26, and VR37 at the postboost time point and prior to infection. The orange diamonds represent VR26 and VR37 at the breakthrough time point. Data are presented in log scale. (C) Levels of antibodies that inhibit ACE2/spike binding in preboost and postboost VRs and in VR21, VR26, VR37, and VR97 at the 1- to 3-week postboost time point. (D) Levels of antibodies that inhibit ACE2/spike binding in postboost VRs 1–3 weeks or 1–3 months after their booster shot and breakthrough VRs 1–3 weeks after symptom onset The orange diamonds represent VR21, VR26, VR37, and VR97. (E) Levels of antibodies that inhibit ACE2/spike binding in paired breakthrough VRs at 1–3 weeks and 4–7 weeks after infection. Statistical comparisons were done using ordinary 1-way ANOVA (unpaired) and Holm-Šidák’s multiple comparison test, with a single pool variance used (A–D). (E) Paired analyses were performed using repeated-measures 1-way ANOVA with Geisser-Greenhouse corrections, and Šidák’s multiple comparison test, with individual variances was computed for each comparison. *P = 0.0332, **P = 0.0021, ***P = 0.0002, ****P < 0.0001.