Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors in two UK longitudinal studies

Abstract

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. Funding: Antibody testing was funded by UK Health Security Agency. The National Core Studies program is funded by COVID-19 Longitudinal Health and Wellbeing - National Core Study (LHW-NCS) HMT/UKRI/MRC (MC_PC_20030 & MC_PC_20059). Related funding was also provided by the NIHR 606 (CONVALESCENCE grant COV-LT-0009). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd and the National Institute for Health Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC.

Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study

“…Our findings are consistent with previous immunology studies that reported higher antibody levels following BNT–BNT versus AZ–AZ, 17 , 18 , 19 including studies in dialysis and kidney transplant recipients. 6 , 20 Higher effectiveness for BNT–BNT versus AZ–AZ has also been reported during the Delta wave in study populations not restricted to individuals with kidney disease.…”

“…The administration of BNT as a third dose appeared to compensate for the discrepancies in protection between AZ- and BNT-primed individuals. This finding is consistent with observational and clinical studies of third-dose immunogenicity in healthy adults 17 , 25 and individuals with kidney disease, 7 , 9 , 26 as well as vaccine effectiveness data from the general population. 27 One previous study explored short-term vaccine effectiveness of BNT as a third dose following AZ or BNT priming among haemodialysis recipients, reporting increased protection against Omicron infection for boosted compared with unboosted individuals and no significant differences according to primary vaccine group.…”

Vaccinia Virus Strain MVA Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Glycoprotein Induces Robust Protection and Prevents Brain Infection in Mouse and Hamster Models

“…The trimeric S protein is a prominent immunological component of the virion surface and plays a crucial role in SARS-CoV-2 binding and entry to the host cell, mediating the interaction of the virus with the cellular receptor angiotensin-converting enzyme 2 (ACE2) and the subsequent fusion of the virus envelope with the host cell membrane. It has been clearly established that the production of S-specific antibodies that can neutralize the virus is crucial to confer protection against SARS-CoV-2 infection [ 4 , 5 , 6 ].…”

Predictors of Breakthrough SARS-CoV-2 Infection after Vaccination

“…Investigations consider vaccine-induced antibody titers as a marker of immune protection from infection or severe COVID-19 illness [ 11 , 12 , 13 ] but no antibody threshold at which to recommend booster dosing after the primary vaccine series has been determined [ 14 ]. Some studies report threshold antibody levels required for 50 or 70% protection against the ancestral and early SARS CoV-2 variant strains but note that the risk of infection changes gradually with the antibody titers [ 15 , 16 , 17 , 18 ]. The World Health Organization (WHO) has established standardized units for antibodies against SARS-CoV-2 (BAU/mL; binding assay); however, reported titers may be affected by the assays used, the vaccinated populations studied and the prevalent viral variant strains [ 16 ], making comparisons between studies difficult.…”