Long term anti-SARS-CoV-2 antibody kinetics and correlate of protection against Omicron BA.1/BA.2 infection

Abstract

Binding antibody levels against SARS-CoV-2 have shown to be correlates of protection against infection with pre-Omicron lineages. This has been challenged by the emergence of immune-evasive variants, notably the Omicron sublineages, in an evolving immune landscape with high levels of cumulative incidence and vaccination coverage. This in turn limits the use of commercially available high-throughput methods to quantify binding antibodies as a tool to monitor protection at the population-level. In this work, we leverage repeated serological measurements between April 2020 and December 2021 on 1'083 participants of a population-based cohort in Geneva, Switzerland, to evaluate anti-Spike RBD antibody levels as a correlate of protection against Omicron BA.1/BA.2 infections during the December 2021-March 2022 epidemic wave. We do so by first modeling antibody dynamics in time with kinetic models. We then use these models to predict antibody trajectories into the time period where Omicron BA.1/BA.2 were the predominant circulating sub-lineages and use survival analyses to compare the hazard of having a positive SARS-CoV-2 test by antibody level, vaccination status and infection history. We find that antibody kinetics in our sample are mainly determined by infection and vaccination history, and to a lesser extent by demographics. After controlling for age and previous infections (based on anti-nucleocapsid serology), survival analyses show reveal a significant reduction in the hazard of having a documented positive SARS-CoV-2 infection during the Omicron BA.1/BA.2 wave with increasing antibody levels, reaching up to a three-fold reduction for anti-S antibody levels above 800 IU/mL (HR 0.30, 95% CI 0.22-0.41). However, we did not detect a reduction in hazard among uninfected participants. Taken together these results indicate that anti-Spike RBD antibody levels, as quantified by the immunoassay used in this study, are an indirect correlate of protection against Omicron BA.1/BA.2 for individuals with a history of previous SARS-CoV-2 infection. Despite the uncertainty in what SARS-COV-2 variant will come next, these results provide reassuring insights into the continued interpretation of SARS-CoV-2 binding antibody measurements as an independent marker of protection at both the individual and population levels.

Serum anti-nucleocapsid antibody level induced after primary infection is an immunological surrogate of protection against SARS-CoV-2 re-infection in hybrid immunity holders

“…[5][6][7] Feng et al demonstrated 80% protection against SARS-CoV-2 infection when the anti-S antibody level was 247 BAU/ml in a ChAdOx1 study cohort. During the Omicron BA.1/BA.2 epidemic period, reductions in infection risk were reported for anti-S antibody titers above 2000 BAU/mL, 800 BAU/mL, and 4810-11233 BAU/mL for symptomatic infections [9][10][11] Additionally, during the Omicron BA.4/5 epidemic period, reductions in infection risk were reported for anti-S antibody titers above 380-1560 BAU/mL, but the anti-S antibody titer thresholds varied according to previous infection histories, and the association between the anti-S antibody titers and the infection risk was not observed in individuals with previous Omicron BA.2 infection. 12 Our results did not estimate an 80% relative risk reduction against infection, even at anti-S antibody titers above 100,000 BAU/mL during the Omicron BA.5 epidemic period.…”

“…[5][6][7] While the prevention of severe disease through vaccination has been confirmed even during the Omicron BA.1/2 and BA.4/5 epidemic periods 8 , higher anti-spike (S) antibody titers against the ancestral strain were required for protection against infection during these periods compared to the pre-Omicron epidemic period. [9][10][11][12] Omicron sublineages tend to be selected for mutations with high humoral immune evasion capabilities, 13 and the protective effect of anti-S antibody titers against the ancestral strain needs to be re-evaluated in response to changes in the antigenicity of the emerging variants. 14 Recently, with the increase in the proportion of infected individuals, it has been reported that not only the neutralizing antibody titers and anti-S antibody titers induced by vaccination but also past infection history are significantly associated with a reduction in infection risk.…”