Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 28, Number 5—May 2022
Research Letter

Cross-Variant Neutralizing Serum Activity after SARS-CoV-2 Breakthrough Infections

Pinkus Tober-Lau1, Henning Gruell1, Kanika Vanshylla1, Willi M. Koch, David Hillus, Philipp Schommers, Isabelle Suárez, Norbert Suttorp, Leif Erik Sander2, Florian Klein2, and Florian Kurth2Comments to Author 
Author affiliations: Charité–Universitätsmedizin Berlin, Berlin, Germany (P. Tober-Lau, W.M. Koch, D. Hillus, N. Suttorp, L.E. Sander, F. Kurth); University of Cologne, Cologne, Germany (H. Gruell, K. Vanshylla, P. Schommers, I. Suárez, F. Klein); German Center for Infection Research, Bonn-Cologne, Germany (F. Klein); Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany (F. Kurth); University Medical Centre Hamburg-Eppendorf, 20359, Hamburg (F. Kurth)

Main Article

Figure

SARS-CoV-2 serum neutralizing titers across variants after postvaccination breakthrough infection. A) Schematic of the study cohort of 2×VI patients and age-matched reference cohorts (1). B) Serum neutralizing activity against Wu01 and SARS-CoV-2 variants in 2×V persons (triangles) and 2×V/I persons (circles). Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. Groups were compared by using the Mann-Whitney test. p values are shown at top. C) Correlation of serum neutralizing activity against SARS-CoV-2 Wu01 (blue) or Omicron (red) and interval between second vaccination and non-Omicron breakthrough infection (Spearman ρ and p values). Breakthrough infections within 3 months (90 days) from vaccination are indicated by light shaded symbols. Solid lines indicate linear regression, and dashed lines indicate 95% CIs. Correlation was determined by Spearman ρ. D) Serum neutralizing activity against SARS-CoV-2 Wu01 (blue) and Omicron (red) in 2×V or 3×V persons (triangles) compared with 2×V/I non-Omicron (circles) or Omicron (triangles) persons after 2 and 3 doses of mRNA vaccine. Only persons with vaccine-to-infection intervals >3 months are shown. Groups were compared by using the Kruskal-Wallis test with the Dunn multiple testing correction. Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. p values are shown at top. Black dotted lines in panels B, C, and D indicate the lower limit of quantification (ID50 = 10); ID50s <10 were imputed to half the lower limit of quantification (ID50 = 5). ID50, 50% inhibitory serum dilution; O, Omicron; pNT, pseudovirus neutralization test; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; V/I, vaccination with subsequent breakthrough infection; Wu01, ancestral (wild-type) SARS-CoV-2 strain; 2xV/I non-Omicron, vaccinated persons with non-Omicron breakthrough infection that occurred 1–8 months after vaccination (circles); 2xV/I Omicron, vaccinated persons with Omicron breakthrough infection that occurred 4–7 months after vaccination (squares); 2xV, vaccinated persons after 2 doses of mRNA vaccine; 3xV, vaccinated persons after 3 doses of mRNA vaccine (triangles).

Figure. SARS-CoV-2 serum neutralizing titers across variants after postvaccination breakthrough infection. A) Schematic of the study cohort of 2×VI patients and age-matched reference cohorts (1). B) Serum neutralizing activity against Wu01 and SARS-CoV-2 variants in 2×V persons (triangles) and 2×V/I persons (circles). Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. Groups were compared by using the Mann-Whitney test. p values are shown at top. C) Correlation of serum neutralizing activity against SARS-CoV-2 Wu01 (blue) or Omicron (red) and interval between second vaccination and non-Omicron breakthrough infection (Spearman ρ and p values). Breakthrough infections within 3 months (90 days) from vaccination are indicated by light shaded symbols. Solid lines indicate linear regression, and dashed lines indicate 95% CIs. Correlation was determined by Spearman ρ. D) Serum neutralizing activity against SARS-CoV-2 Wu01 (blue) and Omicron (red) in 2×V or 3×V persons (triangles) compared with 2×V/I non-Omicron (circles) or Omicron (triangles) persons after 2 and 3 doses of mRNA vaccine. Only persons with vaccine-to-infection intervals >3 months are shown. Groups were compared by using the Kruskal-Wallis test with the Dunn multiple testing correction. Horizontal lines indicate geometric mean ID50s; error bars, 95% CIs. p values are shown at top. Black dotted lines in panels B, C, and D indicate the lower limit of quantification (ID50 = 10); ID50s <10 were imputed to half the lower limit of quantification (ID50 = 5). ID50, 50% inhibitory serum dilution; O, Omicron; pNT, pseudovirus neutralization test; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; V/I, vaccination with subsequent breakthrough infection; Wu01, ancestral (wild-type) SARS-CoV-2 strain; 2xV/I non-Omicron, vaccinated persons with non-Omicron breakthrough infection that occurred 1–8 months after vaccination (circles); 2xV/I Omicron, vaccinated persons with Omicron breakthrough infection that occurred 4–7 months after vaccination (squares); 2xV, vaccinated persons after 2 doses of mRNA vaccine; 3xV, vaccinated persons after 3 doses of mRNA vaccine (triangles).

Main Article

References
  1. Gruell  H, Vanshylla  K, Tober-Lau  P, Hillus  D, Schommers  P, Lehmann  C, et al. mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant. Nat Med. 2022; Epub ahead of print. DOIPubMedGoogle Scholar
  2. Schmidt  F, Muecksch  F, Weisblum  Y, Da Silva  J, Bednarski  E, Cho  A, et al. Plasma neutralization of the SARS-CoV-2 Omicron variant. N Engl J Med. 2022;386:599–601. DOIPubMedGoogle Scholar
  3. Carreño  JM, Alshammary  H, Tcheou  J, Singh  G, Raskin  AJ, Kawabata  H, et al.; PSP-PARIS Study Group. Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron. Nature. 2022;602:682–8. DOIPubMedGoogle Scholar
  4. Nemet  I, Kliker  L, Lustig  Y, Zuckerman  N, Erster  O, Cohen  C, et al. Third BNT162b2 vaccination neutralization of SARS-CoV-2 Omicron infection. N Engl J Med. 2022;386:492–4. DOIPubMedGoogle Scholar
  5. Bates  TA, McBride  SK, Winders  B, Schoen  D, Trautmann  L, Curlin  ME, et al. Antibody response and variant cross-neutralization after SARS-CoV-2 breakthrough infection. JAMA. 2022;327:179–81. DOIPubMedGoogle Scholar
  6. Rössler  A, Riepler  L, Bante  D, von Laer  D, Kimpel  J. SARS-CoV-2 Omicron variant neutralization in serum from vaccinated and convalescent persons. N Engl J Med. 2022;386:698–700. DOIPubMedGoogle Scholar

Main Article

1These authors contributed equally to this article.

2These authors co-led this study.

Page created: February 25, 2022
Page updated: April 19, 2022
Page reviewed: April 19, 2022
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external