Determinants of Antibody Responses to SARS-CoV-2 Vaccines: Population-Based Longitudinal Study (COVIDENCE UK)

Abstract

Antibody responses to SARS-CoV-2 vaccines vary for reasons that remain poorly understood. A range of sociodemographic, behavioural, clinical, pharmacologic and nutritional factors could explain these differences. To investigate this hypothesis, we tested for presence of combined IgG, IgA and IgM (IgGAM) anti-Spike antibodies before and after 2 doses of ChAdOx1 nCoV-19 (ChAdOx1, AstraZeneca) or BNT162b2 (Pfizer-BioNTech) in UK adults participating in a population-based longitudinal study who received their first dose of vaccine between December 2020 and July 2021. Information on sixty-six potential sociodemographic, behavioural, clinical, pharmacologic and nutritional determinants of serological response to vaccination was captured using serial online questionnaires. We used logistic regression to estimate multivariable-adjusted odds ratios (aORs) for associations between independent variables and risk of seronegativity following two vaccine doses. Additionally, percentage differences in antibody titres between groups were estimated in the sub-set of participants who were seropositive post-vaccination using linear regression. Anti-spike antibodies were undetectable in 378/9101 (4.2%) participants at a median of 8.6 weeks post second vaccine dose. Increased risk of post-vaccination seronegativity associated with administration of ChAdOx1 vs. BNT162b2 (adjusted odds ratio (aOR) 6.6, 95% CI 4.2–10.4), shorter interval between vaccine doses (aOR 1.6, 1.2–2.1, 6–10 vs. >10 weeks), poor vs. excellent general health (aOR 3.1, 1.4–7.0), immunodeficiency (aOR 6.5, 2.5–16.6) and immunosuppressant use (aOR 3.7, 2.4–5.7). Odds of seronegativity were lower for participants who were SARS-CoV-2 seropositive pre-vaccination (aOR 0.2, 0.0–0.6) and for those taking vitamin D supplements (aOR 0.7, 0.5–0.9). Serologic responses to vaccination did not associate with time of day of vaccine administration, lifestyle factors including tobacco smoking, alcohol intake and sleep, or use of anti-pyretics for management of reactive symptoms after vaccination. In a sub-set of 8727 individuals who were seropositive post-vaccination, lower antibody titres associated with administration of ChAdOx1 vs. BNT162b2 (43.4% lower, 41.8–44.8), longer duration between second vaccine dose and sampling (12.7% lower, 8.2–16.9, for 9–16 weeks vs. 2–4 weeks), shorter interval between vaccine doses (10.4% lower, 3.7–16.7, for <6 weeks vs. >10 weeks), receiving a second vaccine dose in October–December vs. April–June (47.7% lower, 11.4–69.1), older age (3.3% lower per 10-year increase in age, 2.1–4.6), and hypertension (4.1% lower, 1.1–6.9). Higher antibody titres associated with South Asian ethnicity (16.2% higher, 3.0–31.1, vs. White ethnicity) or Mixed/Multiple/Other ethnicity (11.8% higher, 2.9–21.6, vs. White ethnicity), higher body mass index (BMI; 2.9% higher, 0.2–5.7, for BMI 25–30 vs. <25 kg/m2) and pre-vaccination seropositivity for SARS-CoV-2 (105.1% higher, 94.1–116.6, for those seropositive and experienced COVID-19 symptoms vs. those who were seronegative pre-vaccination). In conclusion, we identify multiple determinants of antibody responses to SARS-CoV-2 vaccines, many of which are modifiable.

Humoral immune response after anti-SARS-CoV-2 vaccine “booster” dose in patients with monoclonal gammopathy of undetermined significance (MGUS)

“…After a mean number of 96 days (range 14–180) from third vaccine dose, all MGUS patients (100%) achieved a titer greater than 50 AU/mL; thus, they were all considered as “responders”. Notably, in contrast with previously reported data, 10 administration of the first two doses of ChAdOx1 was not associated to lower antibody titer compared to that after two BNT162b2 doses. We did not find any correlation between gender (p-value=0.1768), MGUS-subtype (p-value=0.1956), MGUS risk-stratification (p-value=0.1647), sequence of vaccine doses (p-value=0.4144), days from third vaccine dose to blood collection (p-value=0.3347) and titer of anti-spike IgG antibodies.…”

“…After a mean number of 96 days (range 14-180) from third vaccine dose, all MGUS patients (100%) achieved a titer greater than 50 AU/mL; thus, they were all considered as "responders". Notably, in contrast with previously reported data, 10 administration of the first two doses of ChAdOx1 was not associated to lower Then we compared serological response of MGUS patients with those of age and sex matched healthcare workers, enrolled in the study as HCs. It was possible only for 11 patients; the remaining nine ones were older than HCs and therefore not comparable with healthcare workers.…”

Incidence determinants and serological correlates of reactive symptoms following SARS-CoV-2 vaccination

“…A further strength is the use of an ELISA with high sensitivity and specificity that targets three different types of antibody (IgG/IgA/IgM), increasing the probability of identifying a past infection over other studies which primarily use quantitative levels of IgG anti-spike antibodies 16 . Additionally, we used dried blood spots for our sampling: although these yield a low volume of sample and their results may be impacted by variations in haematocrit, their use has been found to significantly reduce processing failures compared with microtubes 17 , which are currently used by large seroprevalence surveys 18 .…”

“…Our study was nested within COVIDENCE UK, which is a prospective longitudinal population-based observational study of coronavirus disease in the UK population ( www.qmul.ac.uk/covidence ) 16 , 17 , 19 . The study was launched on 1 st May 2020, and closed to enrolment on 6 th October 2021.…”

Age and Cytokine Gene Variants Modulate the Immunogenicity and Protective Effect of SARS-CoV-2 mRNA-Based Vaccination

“…However, there is currently limited evidence on factors influencing individual responses to anti-SARS-CoV-2 vaccines. A wide range of sociodemographic, biological, clinical, and nutritional factors have been reported to influence the different production of anti-spike antibodies and their titers after vaccination in people of different ages and ethnicities [ 17 ]. Therefore, individual genetic background, which influences the intensity and quality of the immune and inflammatory response, could also be implicated in the regulation of the vaccine-induced anti-SARS-CoV-2 immune response.…”