Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors

Abstract

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. From cross-sectional antibody testing of 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies (jointly in April-May 2021, and TwinsUK only in November 2021-January 2022), 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.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, 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.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.Lay summaryIn this study, we analysed blood samples from 9,361 participants from two studies in the UK: an adult twin registry, TwinsUK (4,739 individuals); and the Avon Longitudinal Study of Parents and Children, ALSPAC (4,622 individuals). We did this work as part of the UK Government National Core Studies initiative researching COVID-19. We measured blood antibodies which are specific to SARS-CoV-2 (which causes COVID-19). Having a third COVID-19 vaccination boosted antibody levels. More than 90% of people from TwinsUK had levels after third vaccination that were greater than the average level after second vaccination. Importantly, this was the case even in individuals on the UK “Shielded Patient List”. We found that people with lower antibody levels after first vaccination were more likely to report having COVID-19 later on, compared to people with higher antibody levels. People on the UK “Shielded Patient List”, and individuals who reported that they had poorer general health, were more likely to have lower antibody levels after vaccination. In contrast, people who had had a previous COVID-19 infection were more likely to have higher antibody levels following vaccination compared to people without infection. People receiving the Oxford/AstraZeneca rather than the Pfizer BioNTech vaccine had lower antibody levels after one or two vaccinations. However, after a third vaccination, there was no difference in antibody levels between those who had Oxford/AstraZeneca and Pfizer BioNTech vaccines for their first two doses. These findings support having a third COVID-19 vaccination to boost antibodies.

Comparative effectiveness of two- and three-dose 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 16-18 , including studies in dialysis and kidney transplant recipients 6,19 . 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 20,21 .…”

“…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 16,24 and individuals with kidney disease 7,9,25 , as well as vaccine effectiveness data from the general population 26 . 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 27 .…”

Eleven-month SARS-CoV-2 binding antibody decay, and associated factors, among mRNA vaccinees: implications for booster vaccination

“…The optimal timing of booster vaccination remains unclear, with some advocating for annual COVID-19 vaccines [41]. Given the existing evidence demonstrating that SARS-CoV-2 antibody levels are associated with COVID-19 risk [12][13][14] and disease COVID-19 severity [15][16][17], antibody models may play a role in informing booster vaccination strategies. Our 11 month data indicates that antibody levels peak within 1 month, and then decline up to approximately 10 months.…”

“…Given evidence of waning SARS-CoV-2 humoral immune responses after vaccination, booster vaccinations have been implemented in many jurisdictions; however, the optimal timing for boosters remains unclear. There is growing evidence that SARS-CoV-2 antibody levels provide a measure of COVID-19 risk [12][13][14] and COVID-19 severity [15][16][17], a relationship that has been shown to be present even within the Omicron era [18]. Thus, antibody levels may inform decisions regarding the optimal timing of a booster vaccination.…”