In a recent study published on the medRxiv * prepress server, researchers investigated the associations between antibody levels against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the risk of subsequent infection.
Study: Antibody levels after vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors. Image credit: Kateryna Kon / Shutterstock
Fund
Immune responses after SARS-CoV-2 infection or vaccination vary over time and between individuals. Antibodies to the SARS-CoV-2 nucleocapsid protein (N) are obtained in response to infection, but not to vaccination. Therefore, the presence of anti-N antibodies is a valuable substitute for differentiating antibodies caused by infection from vaccine-induced antibodies.
Previous studies have observed a correlation between higher levels of antibodies against spike protein (S) or its receptor binding domain (RBD) after two doses of vaccine and improved protection against subsequent infection. In addition to the temporal effects, the neutralizing capacity of the antibodies differs depending on the virulence and divergence of the S proteins in emerging variants of the ancestral S protein.
The study and conclusions
The researchers evaluated the origins and consequences of the variation in levels of anti-SARS-CoV-2 antibodies after vaccination in the current study. They quantified the antibody levels of participants from two longitudinal cohorts in the United Kingdom: TwinsUK and Avon Longitudinal Study of Parents and Children (ALSPAC).
Antibody levels were determined at two times for 9361 individuals in the ALSPAC and TwinsUK cohorts during April-May 2021 (called Q2, as in the calendar year quarter) and 3575 subjects in the TwinsUK cohort between November 2021 and January 2022 (Q4). Those who received more doses of vaccine were larger and probably enrolled in the UK’s “List of Protected Patients” than participants who received fewer doses.
The prevalence of suspected or confirmed cases of coronavirus disease 2019 (COVID-19) in the second trimester trials was 26% among TwinsUK and 20% in the ALSPAC cohort. However, the positivity of anti-N antibodies was less than 10% in ALSPAC and 12% in TwinsUK. In the fourth trimester, the prevalence of SARS-CoV-2 infection was higher, with 33% of suspected or confirmed cases and 17% depending on levels of anti-N antibodies.
Within the TwinsUK cohort in Q4, the authors observed more significant and sustained antibody levels after the third dose with less variation between individuals compared to the antibody levels of individuals with fewer vaccinations. For example, the mean level of anti-S antibodies was 13,700 units of binding antibody (BAU) / ml after the third vaccination, which was 10 times higher than the levels after the second dose (1300 BAU / ml).
Individuals with the lowest antibody levels had substantial increases in absolute levels after the third dose. TwinsUK subjects sampled two / three weeks after the third vaccination had the highest mean antibody levels for up to 16 weeks. Average levels decreased between two and eight weeks, and after that there was no decline. More time since vaccination was associated with lower antibody levels for individuals sampled between 13 and 33 weeks after the second dose.
In Q2, antibody levels peaked nine weeks after the first dose between TwinsUK and ALSPAC subjects. After the second dose, antibody levels exceeded the test limit from the second week. In the TwinsUK cohort, innovative vaccine infections were reported in 276 (9.2%) individuals between the first vaccination and the fourth trimester. Those who were vaccinated only once in Q2 with a later advanced infection had lower mean Q2 antibody levels (40 BAU / ml) than those who did not experience a rupture infection (57 BAU / ml).
They noted that individuals with the lowest antibody levels in Q2 were more likely to experience innovative infection in univariate (odds ratio, OR: 3.2) and multivariable (OR: 2.9) logistic regression models. An increase in the likelihood of having lower antibody levels after the first vaccination was observed in those on the UK list of protected patients in the TwinsUK (OR: 4) and ALSPAC (OR: 4.1) cohorts. ).
People vaccinated with AstraZeneca’s AZD1222 vaccine were more likely to have lower antibody levels after the first and second vaccinations compared to Pfizer’s BNT162b2 vaccines. However, a double dose of AZD1222 was not associated with lower levels of antibodies after the third vaccination. In the TwinsUK cohort, monozygotic twins (MZs) showed lower mean intra-pair differences in anti-S antibody levels after the third dose relative to dizygotic twins. Intra-pair differences were large for unrelated subjects.
Conclusions
The researchers found great variability in antibody responses after the first vaccination with decreasing variability after the administration of the second and third vaccine doses. Individuals who had low levels of antibodies after the first dose had a high risk of subsequent advanced infection even after new rounds of vaccination.
In addition, an increase in the likelihood of having lower levels of antibodies after vaccination was observed for 1) individuals on the protected patient list, 2) recipients of the first and second doses of the vaccine. AZD1222, 3) those who reported poorer health and 4) those who were prescribed immunosuppressants. However, there were no differences after the third vaccination between individuals who received BNT162b2 or AZD1222 for their first and second vaccinations, which supported the reinforcing effect of the third dose.
These findings suggested that measuring anti-S antibodies induced after the first dose of vaccine could serve as an early indicator to identify those at higher risk for COVID-19 infection in the future.
* Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guided by clinical practice or health-related behavior, or treated as established information.