Neutralizing antibodies after three doses of the BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron-predominant wave

Int J Infect Dis. 2023 Mar:128:347-354. doi: 10.1016/j.ijid.2023.01.023. Epub 2023 Jan 22.


Objectives: To investigate the role of immunogenicity after the third vaccine dose against Omicron infection and COVID-19-compatible symptoms of infection.

Methods: First, we examined vaccine effectiveness (VE) of the third dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of third vaccine recipients, we compared the preinfection live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls who had close contact with patients with COVID-19. Among these cases, we examined the association between NAb levels and the number of COVID-19-compatible symptoms.

Results: Among the 1456 participants for VE analysis, 60 breakthrough infections occurred during the Omicron wave. The third dose VE for infection was 54.6%. Among the third dose recipients, NAb levels against Omicron did not differ between the cases (n = 22) and controls (n = 21). Among the cases, those who experienced COVID-19-compatible symptoms had lower NAb levels against Omicron than those who did not.

Conclusion: The third vaccine dose was effective in decreasing the risk of SARS-CoV-2 infection during Omicron wave compared with the second dose. Among third dose recipients, higher preinfection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection.

Keywords: Breakthrough infection; COVID-19; Neutralizing antibody; Omicron; Third dose.

MeSH terms

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • BNT162 Vaccine
  • Breakthrough Infections
  • COVID-19*
  • Case-Control Studies
  • Humans
  • SARS-CoV-2
  • Vaccines*


  • Antibodies, Neutralizing
  • BNT162 Vaccine
  • Vaccines
  • Antibodies, Viral