Variability in mRNA SARS-CoV-2 BNT162b2 vaccine immunogenicity is associated with differences in the gut microbiome and habitual dietary fibre intake (preprint)

Objective: Little is known about the interplay between gut microbiome and SARS-CoV-2 vaccine immunogenicity. In this prospective observational study, we investigated associations between the gut microbiome, habitual dietary fibre intake, and mRNA vaccine-elicited immune responses, including anti-Spike IgG, avidity, and ACE-2 competition (surrogate neutralization). Design: 16S rRNA sequencing and short-chain fatty acid analyses were undertaken using stool samples collected from 48 healthy individuals at baseline and twelve-weeks after 1st BNT162b2 SARS-CoV-2 vaccine dose. Associations between gut microbiome data and SARS-CoV-2 spike and RBD IgG levels, competitive binding antibodies, and anti-SARS-CoV-2 spike total relative fractional avidity assays were evaluated. A validated dietary fibre intake food frequency questionnaire was also used to correlate habitual dietary fibre intakes with vaccine responses. Results: Our data revealed several baseline bacterial taxa, including Prevotella, Haemophilus and Veillonella (p<0.01), associated with BNT162b2 vaccine responses. Several Bacteroides spp. (p<0.01) as well as Bifidobacterium animalis, (p=0.003), amongst others, were positively associated with antibody avidity. Conversely, concentrations of isovaleric and isobutyric acid were higher in individuals with the lowest SARS-CoV-2 vaccine responses (p<0.01). Classifying participants based on habitual dietary fibre intake identified distinct avidity responses. Conclusion: We showed associations between baseline gut microbiota composition and immunogenicity of BNT162b2 vaccine responses, particularly avidity maturation. We also demonstrate that branched-chain fatty acids and habitual dietary fibre intakes are associated with BNT162b2 vaccine immunogenicity. Together these findings indicate a link between gut microbiome, diet and antibody immunity to SARS-CoV-2 spike protein, suggesting interventions which modulate the gut microbiome could enhance COVID-19 vaccine responses.

Antibody Reactivity Against SARS-CoV-2 in Adults from the Vancouver Metropolitan Area, Canada (preprint)

Background: Quantifying antibody reactivity against multiple SARS-CoV-2 antigens at the population level may help understand individual differences in COVID-19 severity. Pre-existing low antibody cross-reactivity may be particularly prevalent among childcare providers, including pediatric health care workers (HCW) who may be more exposed to circulating coronaviruses.Methods: Cross-sectional study that included adults in the Vancouver area in British Columbia (BC), Canada, between May 17 and June 19, 2020. SARS-CoV-2 seroprevalence was ascertained by measuring total SARS-CoV-2 IgG/M/A antibodies against a recombinant spike (S1) protein and adjusted for bias due to false-positive and false-negative test results. A novel, high sensitivity multiplex assay was also used to profile IgG against four SARS-CoV-2 antigens, SARS-CoV and four circulating coronaviruses.Findings: Among 276 participants (71% HCW), three showed evidence of direct viral exposure, yielding an adjusted seroprevalence of 0.60% [95%CI 0% – 2.71%], with no difference between HCW and non-HCW, or between paediatric and adult HCW. Among the 273 unexposed individuals, 7.3% [95%CI 4.5% – 11.1%], 48.7 [95%CI 42.7% – 54.8%] and 82.4% [95%CI 77.4% – 86.7%] showed antibody reactivity against SARS-CoV-2 RBD, N or Spike proteins, respectively. SARS-CoV-2 reactivity did not significantly correlate with age, sex, did not significantly differ between HCW and non-HCW (prevalence 1.0% vs 1.0%; P =1.00) and between pediatric and adult HCW (0.7% vs 1.6%; P =0.54), and modestly correlated with reactivity to circulating coronaviruses (Spearman rho range: 0.130 to 0.224 for 7 significant (FDR 5%), out of 16 correlations, from 36 correlations tested).Interpretation: A substantial proportion of individuals showed low, but detectable antibody reactivity against SARS-CoV-2 antigens in this population despite low evidence of direct SARS-CoV-2 exposure.Funding Statement: This study was funded by unrestricted funding to PML and an Intramural Research Program of the Vaccine Research Centre (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH)Declaration of Interests: The authors declare no conflicts of interest.Ethics Approval Statement: The study was approved by the University of British Columbia Children’s & Women’s Research Ethic Board (H20-01205).

Antibody reactivity to SARS-CoV-2 in adults from the Vancouver metropolitan area, Canada (preprint)

Background: Quantifying antibody reactivity to SARS-CoV-2 antigens may help understand its effect on COVID-19 severity at the population level. This antibody reactivity may be particularly prevalent among childcare providers, including pediatric health care workers (HCW) who may be more exposed to circulating coronaviruses. Methods: Cross-sectional study that included adults in the Vancouver area in British Columbia (BC), Canada, between May 17 and June 19, 2020. A novel 10-plex antibody assay (IgG) was used to measure antibody reactivity against the spike protein from circulating coronaviruses (229E, NL63, OC43, and HKU1), SARS-CoV, and four SARS-CoV-2 antigens. Seroreactivity from previous viral exposure was ascertained using this assay, and by measuring total SARS-CoV-2 IgG/M/A antibodies against a recombinant spike (S1) protein using a commercial CLIA assay. Findings: Among 276 participants (71% HCW), three showed evidence of direct viral exposure, yielding an adjusted seroprevalence of 0.6% [95%CI 0.2 to 3.1%], with no difference between HCW and non-HCW, or between paediatric and adult HCW. Among the remaining 273 unexposed individuals, 7.3% [95%CI 4.5% to 11.1%], 48.7 [95%CI 42.7% to 54.8%] and 82.4% [95%CI 77.4% to 86.7%] showed antibody reactivity against SARS-CoV-2 RBD, N or Spike proteins, respectively. This reactivity was evenly distributed as a function of age, sex or between paediatric and adult HCW, and partly correlated with reactivity to circulating coronaviruses (Spearman; range: 0.147 to 0.513 for significant correlation after false-discovery rate adjustment at 5%). Interpretation: A substantial proportion of individuals in this population showed antibody reactivity against SARS-CoV-2 antigens despite low serological evidence of SARS-CoV-2 exposure.