Background: SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. Higher levels of SARS-CoV-2 anti-Spike antibodies are known to be associated with increased protection against future SARS-CoV-2 infection. However, variation in antibody levels and risk factors for lower antibody levels following each round of SARS-CoV-2 vaccination have not been explored across a wide range of socio-demographic, SARS-CoV-2 infection and vaccination, and health factors within population-based cohorts.

Methods: Samples were collected from 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies and tested for SARS-CoV-2 antibodies. Cross-sectional sampling was undertaken jointly in April-May 2021 (TwinsUK, N = 4,256; ALSPAC, N = 4,622), and in TwinsUK only in November 2021-January 2022 (N = 3,575). Variation in antibody levels after first, second, and third SARS-CoV-2 vaccination with health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables were analysed. Using multivariable logistic regression models, we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables.

Results: Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months (OR = 2.9, 95% CI: 1.4, 6.0), compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK 'Shielded Patient List' had consistently greater odds (2- to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations.

Conclusions: These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies.


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Cite as

Cheetham, N., Kibble, M., Wong, A., Silverwood, R., Knuppel, A., Williams, D., Hamilton, O., Lee, P., Bridger Staatz, C., Di Gessa, G., Zhu, J., Katikireddi, S., Ploubidis, G., Thompson, E., Bowyer, R., Zhang, X., Abbasian, G., Garcia, M., Hart, D., Seow, J., Graham, C., Kouphou, N., Acors, S., Malim, M., Mitchell, R., Northstone, K., Major-Smith, D., Matthews, S., Breeze, T., Crawford, M., Molloy, L., Kwong, A., Doores, K., Chaturvedi, N., Duncan, E., Timpson, N. & Steves, C. 2023, 'Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors', eLife. https://doi.org/10.7554/eLife.80428

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Last updated: 02 November 2023
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