Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 24:14:1083523.
doi: 10.3389/fimmu.2023.1083523. eCollection 2023.

Kinetics of SARS-CoV-2 neutralizing antibodies in Omicron breakthrough cases with inactivated vaccination: Role in inferring the history and duration of infection

Aidibai Simayi  1   2 , Chuchu Li  3 , Cong Chen  4 , Yin Wang  5 , Chen Dong  3 , Hua Tian  3 , Xiaoxiao Kong  3 , Lu Zhou  3 , Jiefu Peng  3 , Shihan Zhang  1   2 , Fengcai Zhu  3   6   7 , Jianli Hu  3 , Ke Xu  3 , Hui Jin  1   2 , Huafeng Fan  8 , Changjun Bao  3   9 , Liguo Zhu  3   6   7   10
Affiliations

Kinetics of SARS-CoV-2 neutralizing antibodies in Omicron breakthrough cases with inactivated vaccination: Role in inferring the history and duration of infection

Aidibai Simayi et al. Front Immunol. .

Abstract

Background: The quantitative level and kinetics of neutralizing antibodies (NAbs) in individuals with Omicron breakthrough infections may differ from those of vaccinated individuals without infection. Therefore, we aimed to evaluate the difference in NAb levels to distinguish the breakthrough cases from the post-immunized population to identify early infected person in an outbreak epidemic when nasal and/or pharyngeal swab nucleic acid real-time PCR results were negative.

Methods: We collected 1077 serum samples from 877 individuals, including 189 with Omicron BA.2 breakthrough infection and 688 post-immunized participants. NAb titers were detected using the surrogate virus neutralization test, and were log(2)-transformed to normalize prior to analysis using Student's unpaired t-tests. Geometric mean titers (GMT) were calculated with 95% confidence intervals (CI). Linear regression models were used to identify factors associated with NAb levels. We further conducted ROC curve analysis to evaluate the NAbs' ability to identify breakthrough infected individuals in the vaccinated population.

Results: The breakthrough infection group had a consistently higher NAb levels than the post-immunized group according to time since the last vaccination. NAb titers in the breakthrough infection group were 6.4-fold higher than those in the post-immunized group (GMT: 40.72 AU/mL and 6.38 AU/mL, respectively; p<0.0001). In the breakthrough infection group, the NAbs in the convalescent phase were 10.9-fold higher than in the acute phase (GMT: 200.48 AU/mL and 18.46 AU/mL, respectively; p<0.0001). In addition, the time since infection, booster vaccination, and the time since last vaccination were associated with log(2)-transformed NAb levels in the breakthrough infection group. ROC curve analysis showed that ROC area was largest (0.728) when the cut-off value of log(2)-transformed NAb was 6, which indicated that NAb levels could identify breakthrough infected individuals in the vaccinated population.

Conclusion: Our study demonstrates that the NAb titers of Omicron BA.2 variant breakthrough cases are higher than in the post-immunized group. The difference in NAb levels could be used to identify cases of breakthrough infection from the post-immunized population in an outbreak epidemic.

Keywords: Omicron variant; SARS-CoV-2; breakthrough infection; inactive CoronaVac; neutralizing antibody.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow chart of study enrollment.
Figure 2
Figure 2
Kinetics and quantitative comparison of NAb levels over time. (A) Trends in NAb after the onset of breakthrough cases. (B) Trends in NAbs in breakthrough cases and post-immunized groups with time since the last vaccination. (C) Comparison of NAbs quantification in breakthrough cases and post-immunized group. (D) Comparison of NAbs in the acute phase and convalescent phase of breakthrough cases. (E) Comparison of NAbs in the acute phase, convalescent phase, and post-immunized group. Dark horizontal lines for each group denote sample medians, and the error bars and dotted lines indicate the interquartile range. ****P < 0.0001.
Figure 3
Figure 3
Changes in NAbs with age. (A) Changes in NAbs with age in breakthrough cases. (B) Changes in NAbs with age during the acute phase and convalescent phase. Each circle and triangle represent the titer for a serum sample. Note: Breakthrough cases were included from February 14, 2022, to May 30, 2022, post-immunized groups were recruited from August 10, 2021, to August 20, 2021.
Figure 4
Figure 4
Impact of inactivates SARS-CoV-2 vaccination to NAbs against Omicron BA.2 variant in breakthrough cases. (A) Breakthrough case classification analysis according to the time since the last vaccination to sampling. (B) Trends in NAb over time for different vaccination doses.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. CDC COVID-19 Vaccine Breakthrough Case Investigations Team . COVID-19 vaccine breakthrough infections reported to CDC - united states, January 1–April 30, 2021. MMWR Morb Mortal Wkly Rep (2021) 70(21):792–3. doi: 10.15585/mmwr.mm7021e3 - DOI - PMC - PubMed
    1. Centers for Disease Control and Prevention . When you’ve been fully vaccinated. Available at: https://www.cdc.gov/coronavirus/2019-ncov/vaccines/fully-vaccinated.html (Accessed 8 November 2021).
    1. Di Fusco M, Moran MM, Cane A, Curcio D, Khan F, Malhotra D, et al. . Evaluation of COVID-19 vaccine breakthrough infections among immunocompromised patients fully vaccinated with BNT162b2. J Med Econ (2021) 24(1):1248–60. doi: 10.1080/13696998.2021.2002063 - DOI - PubMed
    1. Ai J, Zhang H, Zhang Y, Lin K, Zhang Y, Wu J, et al. . Omicron variant showed lower neutralizing sensitivity than other SARS-CoV-2 variants to immune sera elicited by vaccines after boost. Emerg Microbes Infect (2022) 11(1):337–43. doi: 10.1080/22221751.2021.2022440 - DOI - PMC - PubMed
    1. Viana R, Moyo S, Amoako DG, Tegally H, Scheepers C, Althaus CL, et al. . Rapid epidemic expansion of the SARS-CoV-2 omicron variant in southern Africa. Nature (2022) 603:679–86. doi: 10.1038/s41586-022-04411-y - DOI - PMC - PubMed

Publication types