Age Dependent Reduction of Neutralization Capacities Against Delta Variant Five Months Post-Vaccination (BNT162b2)

Background: Long-term control of SARS-CoV-2 via vaccination has been confounded by the introduction of the Delta variant (B1.617.2). Herein, we assessed Delta variant-specific effectiveness of BNT162b2 and characterize Delta-driven breakthrough COVID-19 cases with known-time-since-vaccination.Methods: In this longitudinal, prospective study (January 21 to September 01 2021), we obtained samples from naïve and convalescent individuals including those vaccinated with BNT162b2 to evaluate the implications of the Delta variant. Serology profile (antibodies against S and N protein) and live-virus based neutralization capacities against the B.1 lineage virus and the Delta variant were assessed, while controlling for age.Findings: 99 eligible participants including 85 naïve and 14 convalescent individuals at the initiation of vaccination, were enrolled. In naïve vaccinated individuals, neutralizing capacity against a clinical isolate of the SARS-CoV-2 Delta variant was reduced 4.85-fold compared to the basal B.1 lineage. Further, individuals ≥60 years of age (yoa) have significantly lower neutralization capacities against the Delta variant than younger vaccinated individuals (<60 yoa). Vaccinated participants who were naturally infected prior to the initiation of vaccination exhibited greater neutralization capacities against Delta variant compared to naïve vaccinated individuals. We further identified five breakthrough COVID-19 disease cases attributed to the Delta variant (BC19Δ cases) and demonstrate in vitro infectiousness. BC19Δ cases were more likely to occur in older male individuals with lower neutralizing capacity (EC50 < 117). Interestingly, we observed that BC19Δ cases exhibited a delayed or absent antibody response to the N-protein, suggesting limited within-host exposure to the virus overall.Interpretation: Our data demonstrate 1) an overall significant reduction in neutralizing capacity to the Delta variant relative to the original lineage and 2) that, when stratifying by age, individuals ≥60 yoa have significantly reduced capacity to neutralize live virus compared to individuals < 60 yoa, therefore, suggesting a broader age-range for Pfizer BNT162b2 booster recommendations.Funding: The study was partially funded by Ortho Clinical Diagnostics and Merck Sharp & Dohme Corp. BioInfoExperts funding was provided by National Science Foundation SBIR Awards #1830867 and #2027424Declaration of Interest: None to declare. Ethical Approval: The study protocol was reviewed and approved by Woman’s Hospital Foundation Institutional Review Board protocol# RP-20-029, approved on January 22, 2021