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. 2022 Sep 8:13:964525.
doi: 10.3389/fimmu.2022.964525. eCollection 2022.

Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity

Arne Søraas  1 , Gunnveig Grødeland  2   3 , Beathe Kiland Granerud  1   3   4 , Thor Ueland  3   5   6 , Andreas Lind  1 , Børre Fevang  5   7 , Sarah L Murphy  3   5 , Camilla Huse  3   5 , Anders Benteson Nygaard  1 , Anne Katrine Steffensen  1   3 , Huda Al-Baldawi  3 , Mona Holberg-Petersen  1 , Lise Lima Andresen  1 , Camilla Ågnes  5 , Trine Ranheim  5 , Ylva Schanke  5 , Mette Istre  1 , John Arne Dahl  1 , Adity Chopra  2 , Susanne Dudman  1   3 , Mari Kaarbø  1 , Jan Terje Andersen  3   8 , Eline Benno Vaage  2 , Trung The Tran  2 , John Torgils Vaage  2   3 , Annika E Michelsen  3   5 , Fredrik Müller  1   3 , Pål Aukrust  3   5   6   7 , Bente Halvorsen  3   5 , Tuva B Dahl  5   9 , Jan Cato Holter  1   3 , Fridtjof Lund-Johansen  2   10
Affiliations

Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity

Arne Søraas et al. Front Immunol. .

Erratum in

Abstract

Background: Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals.

Methods: We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively.

Findings: Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters.

Interpretation: The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant.

Funding: The study was funded by the Oslo University Hospital, and by grants from The Coalition for Epidemic Preparedness Innovations, Research Council of Norway (no 312780, 324272), South-Eastern Norway Regional Health Authority (no 2019067, 2021071, 10357, 2021047, 33612, 2021087, 2017092), EU Horizon 2020 grant no 848099, a philantropic donation from Vivaldi Invest A/S, and The European Virus Archive Global.

Keywords: Breakthrough infection; SARS-CoV-2; antibody; cellular immunity; human; vaccine.

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Conflict of interest statement

Author AS reports being an employee and shareholder at Age Labs outside of the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial and financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Viral load. (A) Correlation between viral load and days after symptom onset during the observation period. Thin blue/red lines represent paired samples while thick blue/red lines represent regression curves for the whole group (Omicron or Delta). (B) Viral load shown as Tukey-plots at inclusion (T1) and one week follow-up (T2) according to infection with Omicron or Delta. Differences in viral load at T1 and T2 were compared by ANCOVA, adjusting for symptom days: *p<0.05. ns, not significant.
Figure 2
Figure 2
Early immune responses in individuals infected with Omicron or Delta. (A) Results from whole blood IFNγ release assay (IGRA, IU/ml) in samples harvested from the same individuals with an interval of 8-10 days. T1: inclusion, T2: one week follow up. (B–D) The bar graphs show relative levels (log 10) of antibodies to RBD and the nucleocapsid protein in samples described under (A, B) Individuals with confirmed Omicron infection, (C): Delta infection, (D): vaccinated individuals with no history of SARS-CoV-2 infection. ***p<10-5, **p<10-3, *p<10-2. Source data are found in Supplemental Table 1 .
Figure 3
Figure 3
Neutralizing antibodies in individuals infected with Omicron or Delta. The plots show inhibition of ACE2-binding to RBD from SARS-CoV-2 wild type or Omicron (BA.1) in % of control (sera with no detectable anti-RBDwt IgG). T1: inclusion, T2: one week follow up. (A) Individuals with Omicron infection. (B) Individuals with Delta infection.
Figure 4
Figure 4
Kinetics of antibody responses in individuals infected with Omicron or Delta. The scatter plots show individual data after infection with Omicron (A–F) or Delta (G–L) plotted at days after symptoms onset. (A, G) Viral load in nasopharyngeal swabs. (B–E) and (H–K) Relative levels of antibodies to indicated antigen (y-axis, log10). (F, L) T-cell responses by IFNγ release assay. Blue and red dots indicate the first and second sample obtained at 4-14 days intervals, respectively. Enlarged black dots indicate samples from an unvaccinated individual obtained at 9 or 16 days after symptom onset. Source data are found in Supplemental Table 1 .
Figure 5
Figure 5
(A–D): The scatter plots show relative levels of IgG antibodies to indicated antigen in individuals infected with Omicron. Enlarged black dots correspond to unvaccinated individual (see Fig. 4 ). (A): IgG responses against spike-full length protein (Spike FL) from the SARS-CoV-2 Wuhan strain (y-axis) and the S2 domain of seasonal coronavirus OC43 (S2-OC43) (x-axis). (B): IgG responses against Spike aa 810-830 (y-axis) and aa 1146-1166 (x-axis): linear peptide antigens that are conserved in the S2 domains of spike proteins in SARS-CoV-2 and seasonal coronaviruses OC43 and HKU1(15)]. (C): IgG responses against the S1 domains from seasonal coronaviruses HKU1 and OC43, respectively (S1 HKU1/OC43). (D): IgG responses against influenza (y-axis) and rhinovirus (x-axis).
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