Abstract
SARS-CoV-2 variants of concern have continuously evolved and may erode vaccine induced immunity. In this observational cohort study, we determine the risk of breakthrough infection in a ...fully vaccinated cohort. SARS-CoV-2 anti-spike IgG levels were measured before first SARS-CoV-2 vaccination and at day 21–28, 90 and 180, as well as after booster vaccination. Breakthrough infections were captured through the Danish National Microbiology database. incidence rate ratio (IRR) for breakthrough infection at time-updated anti-spike IgG levels was determined using Poisson regression. Among 6076 participants, 127 and 364 breakthrough infections due to Delta and Omicron variants were observed. IRR was 0.29 (95% CI 0.15–0.56) for breakthrough infection with the Delta variant, comparing the highest and lowest quintiles of anti-spike IgG. For Omicron, no significant differences in IRR were observed. These results suggest that quantitative level of anti-spike IgG have limited impact on the risk of breakthrough infection with Omicron.
•Hybrid-immunity (both vaccine induced and natural immunity) to SARS-CoV-2 is common.•Hybrid-immunity has an important impact on the antibody trajectories.•More antibodies were seen in people with ...hybrid compared to vaccine-only immunity.•Antibodies declined slower in people with hybrid compared to vaccine-only immunity.•People with comorbidities had lower antibody levels independent of hybrid-immunity.
This study aimed to compare antibody trajectories among individuals with SARS-CoV-2 hybrid and vaccine-induced immunity.
Danish adults receiving three doses of BTN162b2 or mRNA-1237 were included prior to first vaccination (Day 0). SARS-CoV-2 anti-spike IgG levels were assessed before each vaccine dose, at Day 90, Day 180, 28 days after 3rd vaccination (Day 251), Day 365, and prior to 4th vaccination (Day 535). SARS-CoV-2 PCR results were extracted from the national microbiology database. Mixed-effect multivariable linear regression investigated the impact of hybrid-immunity (stratified into 4 groups: no hybrid immunity, PCR+ prior to 3rd dose, PCR+ after 3rd dose and before Day 365, PCR+ after Day 365) on anti-spike IgG trajectories.
A total of 4,936 individuals were included, 47% developed hybrid-immunity. Anti-spike IgG increases were observed in all groups at Day 251, with the highest levels in those PCR+ prior to 3rd dose (Geometric Mean; 535,647AU/mL vs. 374,665AU/mL with no hybrid-immunity, P<0.0001). Further increases were observed in participants who developed hybrid immunity after their 3rd dose. Anti-spike IgG levels declined from Day 251-535 in individuals without hybrid-immunity and in those who developed hybrid-immunity prior to their 3rd dose, with lower rate of decline in those with hybrid-immunity.
Hybrid-immunity results in higher and more durable antibody trajectories in vaccinated individuals.
Abstract
Background
Side effects to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are a key concern contributing to vaccine hesitancy, but more individuals may be encouraged ...if SARS-CoV-2 vaccines were known to lead to a stronger immune response.
Methods
Included were adult participants from the Danish National Cohort Study of Effectiveness and Safety of SARS-CoV-2 Vaccines (ENFORCE) who completed a questionnaire to assess systemic reactions following SARS-CoV-2 vaccination (BTN162b2, mRNA-1273, ChAdOx1) and had SARS-CoV-2 spike immunoglobulin G (IgG) levels measured at baseline and post–vaccine. A symptom score was developed to measure severity of systemic adverse reactions (+1 for each moderate, +2 for each severe). Post–vaccination SARS-CoV-2 spike IgG levels were compared between participants with different scores using multivariable linear regression.
Results
A total of 6528 participants were included (56.3% females; median age interquartile range, 64 54–75 years). After the first vaccination, no association was found between symptom score and post–vaccine dose spike IgG level (P = .575). Following the second vaccination, significantly higher spike IgG levels were observed according to higher symptom scores (P < .001); adjusted geometric mean ratios were 1.16 (95% CI, 1.04–1.30), 1.24 (95% CI, 1.09–1.41), 1.25 (95% CI, 1.06–1.46), and 1.21 (95% CI, 1.08–1.35), for scores of 2, 3, 4, and ≥5, respectively, compared with a score of 0. After adjustment for pre–vaccine dose spike IgG, this association was attenuated.
Conclusions
An association was found between more severe adverse reactions and stronger antibody response after the second vaccination but not the first, likely attributed to higher levels of preexisting immunity gained from response to first vaccination. Regardless of side effects, most people experienced an effective immune response following vaccination.
Greater severity of self-reported systemic adverse reactions after second SARS-CoV-2 vaccination was significantly associated with higher antibody levels against the SARS-CoV-2 spike protein in a cohort study over 6500 individuals. This may reflect pre-existing immunity, likely acquired from first immunization.
SARS-CoV-2 Omicron quickly spread globally, also in regions with high vaccination coverage, emphasizing the importance of exploring the immunological requirements for protection against Omicron ...breakthrough infection.
The test-negative matched case-control study (N = 964) characterized Omicron breakthrough infections in triple-vaccinated individuals from the ENFORCE cohort. Within 60 days before a PCR test spike-specific IgG levels were significantly lower in cases compared to controls (GMR 95% CI for BA.2: 0.83 0.73–0.95, p = 0.006). Multivariable logistic regression showed significant associations between high antibody levels and lower odds of infection (aOR 95% CI for BA.2 spike-specific IgG: 0.65 0.48–0.88, p = 0.006 and BA.2 ACE2-blocking antibodies: 0.46 0.30–0.69, p = 0.0002). A sex-stratified analysis showed more pronounced associations for females than males.
High levels of vaccine-induced antibodies provide partial protection against Omicron breakthrough infections. This is important knowledge to further characterize a threshold for protection against new variants and to estimate the necessity and timing of booster vaccination.
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•High antibody levels are associated with low odds of Omicron breakthrough infection•Vaccine-induced antibodies are an immune marker of protection against infection•Sex stratification revealed a clear association for females in particular
Immunology; Molecular medicine; Immune response
