SARS-CoV-2 neutralising antibody activity in a highly vaccinated population: Longitudinal serology studies in Singapore

  1. Hannah E Clapham
  2. Wanni Chia
  3. Jinyan Zhang
  4. Lin-Fa Wang
  5. Clarence C Tam

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Abstract

Background

There is continuing uncertainty regarding the longevity of immunological responses to both SARS-CoV-2 natural infection and COVID-19 vaccines.

Methods

We analysed data from two serological cohorts in Singapore among residents of a COVID-19 affected migrant worker dormitory between May-July 2020, and among mRNA COVID-19 vaccine recipients between May 2021 and January 2022. We compared SARS-CoV-2 neutralising antibody levels by age group, sex, presence of pre-existing medical conditions, type of mRNA vaccine received and number of doses received. We investigated the effect of time since infection or vaccination on antibody levels in naturally infected individuals and two- and three-dose vaccinees.

Results

After two vaccine doses, neutralising antibody responses were higher in Spikevax (Moderna) recipients, females, younger individuals and those with no underlying medical conditions. However, antibody levels waned to similar levels in all groups over time. A third dose boosted these to similarly high levels in all groups. Waning was apparent among two-dose but not three-dose recipients over a period of six months. Both two and three-dose vaccine recipients showed consistently higher neutralising antibody levels compared with naturally infected individuals over the 12-week period following infection or vaccination.

Conclusions

Our findings support the broad use of booster doses to improve population protection from COVID-19. However, recent increases in transmission of new SARS-CoV-2 variants, even in the presence of high levels of neutralising antibody in a highly vaccinated population, point to vaccine breakthrough as an important mechanism for maintaining SARS-CoV-2 circulation and indicate the need for variant-specific or universal COVID-19 vaccines.

Summary

Younger individuals, females and those with no pre-existing conditions have higher neutralising antibody levels after two doses of COVID-19 mRNA vaccine. Subsequently these wane to levels seen in other groups. A booster dose promotes similarly high levels in all groups.

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    SciScore for 10.1101/2022.05.29.22275748: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsIRB: Analyses were performed in R version 4.1.[4] Ethics statement: The community cohort study was approved by the National University of Singapore institutional review board (reference H-20-032).
    Field Sample Permit: The migrant worker cohort study was approved by the Singapore Ministry of Health under the Infectious Diseases Act (Schedule 59A) as part of the national public health response to the COVID-19 epidemic.
    Sex as a biological variable1] The migrant worker cohort included 541 adult males aged 19-59 years residing in a COVID-19 affected dormitory and who provided blood samples in May 2020 and subsequently after two and six weeks.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    At the height of the Omicron wave in early March, two-dose vaccine recipients had a 3.5 times higher risk of being critically ill and intubated in an intensive care unit compared with three-dose vaccinees; the relative risk among unvaccinated individuals was 7.5 times higher.[5] There are two important caveats. First, the sVNT assay used in this study was developed based on the ancestral SARS-CoV-2 strain; neutralising activity specifically against the Delta and Omicron variants is likely to be lower. This is reflected in the dramatic rises in Delta and Omicron transmission in Singapore in late 2021 and early 2022 despite very high levels of vaccine uptake, which coincide with the easing of travel restrictions and social distancing measures. Second, there is continuing uncertainty regarding the relative protection afforded by previous infection and vaccination, as well as the role of neutralising antibodies in immune protection. A recent systematic review suggested that previous infection provided equivalent protection from COVID-19 compared with two doses of mRNA vaccine,[6] although other studies have shown superior protection from two doses of vaccine.[7,8] Our findings indicate considerably lower neutralising antibody levels following natural infection relative to two and three vaccine doses. A major consideration is that infections in our migrant worker cohort were mild or asymptomatic, which tend to elicit lower, more rapidly waning neutralising antibody responses.[9] F...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2022.05.29.22275748v1 on medRxiv