Antibody responses and correlates of protection in the general population after two doses of the ChAdOx1 or BNT162b2 vaccines

Abstract

Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2–3 months after two ChAdOx1 doses, for 5–8 months after two BNT162b2 doses in those without prior infection and for 1–2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable.

Titers of antibodies the receptor-binding domain (RBD) of ancestral SARS-CoV-2 are predictive for levels of neutralizing antibodies to multiple variants

“…Current diagnostic assays for anti-RBDwt titers are not interchangeable, even when results are converted to BAU/ml 39 . Thus, the median titers reported for sera collected from healthy individuals after two doses of mRNA vaccines vary by more than seven-fold (959 to 7812 BAU/ml) 1,2,6,7 . Variation in samples used as standards in different assays and laboratories is likely to be a contributing factor.…”

“…Thus, the neutralization titers corresponding to 90% vaccine efficacy against symptomatic COVID-19 varied by more than ten-fold in two clinical trials 1,2 . Titers reported for binding antibodies (binding antibody units per milliliter, BAU/ml) after two doses of mRNA vaccines vary by seven-fold 1,2,[6][7][8] . There is therefore an unmet need for standardized high-throughput assays that can be used to monitor bindingand neutralizing antibodies against different SARS-CoV-2 variants at the individual level.…”

“…Fig 6. Groups identified by multi-IgG-ACE2-RBD correspond to defined ranges of binding antibody units per milliliter (BAU/ml).…”

Serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine in lung transplant recipients

“…The lower and upper detection limits of the assay were 4.81 BAU/ml and 2080 BAU/ml, respectively. Previous studies have suggested that antibody levels >94 BAU/mL after two BNT162b2 vaccine doses associated with 67% of individuals being protected against infection with the delta variant [ 8 ], and antibody levels >300 BAU/mL after two mRNA-1273 doses associated with 90% vaccine efficacy. We have evaluated the vaccine response in this cohort in relation to those tresholds [ 9 ].…”

Re: Vaccine effectiveness of ChAdOx1 nCoV-19 against COVID-19 in a socially vulnerable community in Rio de Janeiro, Brazil by Ranzani et al.

“…The infectivity, immune escape ability and pathogenicity of different mutants are different, which may cause confusion in the evaluation of vaccine effectiveness. Third, this analysis fails to account for potentially important confounding factors, including previous COVID-19 infection, populations with more sustained immune protection and possibly greater emphasis on personal protection 4 , such as wearing masks, that can influence the assessment of vaccine effectiveness. Fourth, the novel coronavirus vaccine may have cross-protection against other pathogens, leading to the conclusion that the vaccine protection effect is low.…”