The levels of vaccine-induced neutralizing antibodies (NAbs) against Omicron were much lower than those against Delta and former SARS-CoV-2 strains, even after the third dose [6,7], and such a low level of variant-specific immunogenicity may contribute to poor protection against Omicron infection. Epidemiological evidence around the association between preinfection humoral immunity and the risk of breakthrough infection during the Wuhan (wild-type) Alpha- Alloepipregnanolone and Delta-dominant waves is usually inconsistent [8]. 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 experienced 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 contamination 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 contamination. Contrarily, they may be associated with fewer symptoms of contamination. Keywords: Omicron, Third dose, COVID-19, Breakthrough contamination, Neutralizing antibody Introduction During the ongoing COVID-19 pandemic, the waning of the second vaccine-induced immunogenicity over time [1,2] and the emergence of variants of concerns, such as Delta and Omicron, have led many countries to adapt the booster (third) vaccine campaign. Observational studies have shown that a third dose of existing messenger RNA (mRNA) vaccines is still effective against the infection with Delta and Omicron variants and hospitalization [3], [4], [5]; however, the vaccine effectiveness (VE) of the third dose against Omicron contamination is lower than that against Delta [3,4]. The levels of vaccine-induced neutralizing antibodies (NAbs) against Omicron were much lower than those against Delta and former SARS-CoV-2 strains, even after the third dose [6,7], and such a low level of variant-specific immunogenicity may contribute to poor Alloepipregnanolone protection against Omicron contamination. Epidemiological evidence around the association between preinfection humoral immunity and the risk of breakthrough contamination during the Wuhan (wild-type) Alpha- and Delta-dominant waves is usually inconsistent [8]. Several studies have shown an inverse relationship between vaccine-induced antibody levels and Alloepipregnanolone contamination risk, whereas others have suggested that contamination occurs irrespective of the antibody levels. Data regarding the association between vaccine-induced immunogenicity and contamination risk during the Omicron epidemic are limited [9], which has increased transmissibility and high immune evasion. VE studies have reported a higher ratio of asymptomatic patients to overall infected patients in vaccinated patients with COVID-19 than in unvaccinated patients [10,11], suggesting a suppressive role of the vaccine against symptoms of contamination. It is of interest to determine whether preinfection NAb levels are a determinant of symptomatic episodes during breakthrough contamination. The aim of the current study was to investigate the role of immunogenicity after the third vaccine dose against Omicron contamination and COVID-19-compatible symptoms. First, we examined the VE of the third dose relative to the second dose during the Omicron dominant wave among the staff of a tertiary hospital in Tokyo. In a case-control study nested in a cohort of third vaccine recipients, we compared the preinfection live-virus NAb levels against Omicron after the third dose between breakthrough cases and their controls who were in close contact with patients with COVID-19. In addition, we examined the association between preinfection NAb and the number of COVID-19-compatible symptoms experienced during the Omicron wave. Methods Study establishing In the National Center for Global Health and Medicine (NCGM), Japan, a repeat serological study was launched in July 2020 to monitor the spread of SARS-CoV-2 contamination among Rabbit Polyclonal to CATL1 (H chain, Cleaved-Thr288) the staff during the COVID-19 pandemic. The details of the study have been reported elsewhere [12]. As of March 2022, we have completed five surveys, each of which measured the levels of anti-SARS-CoV-2 nucleocapsid and spike (from the second survey onward) protein antibodies for all those participants using both the Abbott and Roche assays; the serum samples were stored at -80C, and information on COVID-19-related factors (vaccination, occupational contamination risk, infection-prevention practices, history of close contact with patients with COVID-19, COVID-19-compatible symptoms, and so on) were collected using questionnaires. Self-reported vaccination status was validated using the information provided by the NCGM Labor Office, if any. We recognized COVID-19 cases among study participants from your records of patients with COVID-19 maintained by the NCGM Hospital Infection-Prevention and Control Unit, which provided information on the date of diagnosis, diagnostic procedure, possible route of infection (close contact), symptoms, hospitalization, Alloepipregnanolone return to work for all cases, and virus strain and cycle threshold values for those diagnosed at the NCGM. Written informed consent was obtained from all participants. Alloepipregnanolone This study was approved by the NCGM ethics committee (approval number: NCGM-G-003598). Study for the effectiveness of the third vaccine dose relative to the second.