Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach

Abstract

With the ongoing evolution of the SARS-CoV-2 virus updated vaccines may be needed. We fitted a model linking immunity levels and protection to vaccine effectiveness data from England for three vaccines (Oxford/AstraZeneca AZD1222, Pfizer-BioNTech BNT162b2, Moderna mRNA-1273) and two variants (Delta, Omicron). Our model reproduces the observed sustained protection against hospitalisation and death from the Omicron variant over the first six months following dose 3 with the ancestral vaccines but projects a gradual waning to moderate protection after 1 year. Switching the fourth dose to a variant-matched vaccine against Omicron BA.1/2 is projected to prevent nearly twice as many hospitalisations and deaths over a 1-year period compared to administering the ancestral vaccine. This result is sensitive to the degree to which immunogenicity data can be used to predict vaccine effectiveness and uncertainty regarding the impact that infection-induced immunity (not captured here) may play in modifying future vaccine effectiveness.

Predicting Vaccine Effectiveness for Hospitalization and Symptomatic Disease for Novel SARS-CoV-2 Variants Using Neutralizing Antibody Titers

“…Some previous studies had limited datasets for VE for severe disease, which resulted in large uncertainty intervals for VE estimates at low neutralizing antibody titers [ 13 , 14 ], which is problematic for current virus variants. Other studies used data from a single population, and relationships between VE and neutralizing antibody titers for this population differed substantially from other studies [ 15 ]. We included a far larger dataset that encompasses more of the variation in the global population than previous studies.…”

“…Following a similar approach to previous studies [ 13 , 14 , 15 , 17 , 23 ], we calculated neutralizing antibody titer ratios (NATRs) as follows. First, we collected data on mean neutralizing antibody titers for SARS-CoV-2 variants, including wild type (WT) (including D614G), Alpha, Beta, Gamma, Delta, and three Omicron variant sub-lineages (BA.1, BA.2, and BA.4/5) ( Table S1 ).…”

“…Instead, it compared vaccine effectiveness estimates to model predictions from an earlier study [ 13 ]. Finally, a more recent study fit models using data from England to estimate VE against mild disease, hospitalization, and death for Delta and Omicron [ 15 ]. These and other studies [ 16 , 17 , 18 , 19 ] provided strong evidence for a correlation between neutralizing antibodies and protection against symptomatic and severe disease, but in all studies, the datasets used to fit the models were limited, either in the range of neutralizing antibody titers examined [ 13 , 14 , 17 , 18 , 19 ], resulting in substantial uncertainty (particularly for models of severe disease [ 13 , 14 , 17 ]), or in the geographic scale of populations studied [ 15 , 16 ].…”

“…Finally, a more recent study fit models using data from England to estimate VE against mild disease, hospitalization, and death for Delta and Omicron [ 15 ]. These and other studies [ 16 , 17 , 18 , 19 ] provided strong evidence for a correlation between neutralizing antibodies and protection against symptomatic and severe disease, but in all studies, the datasets used to fit the models were limited, either in the range of neutralizing antibody titers examined [ 13 , 14 , 17 , 18 , 19 ], resulting in substantial uncertainty (particularly for models of severe disease [ 13 , 14 , 17 ]), or in the geographic scale of populations studied [ 15 , 16 ]. All currently circulating SARS-CoV-2 variants are highly immune evasive relative to the initial SARS-CoV-2 variants, making predictions and appropriate uncertainty at low neutralizing antibody titers critical for any prudent use in guiding vaccine decision making [ 20 ].…”

Cost-effective boosting allocations in the post-Omicron era of COVID-19 management

“…30 We could have explored more optimistic values for bivalent vaccine effectiveness, which may lead to greater estimated benefits. 31 Neither social restrictions nor antiviral agents were included, given that neither are presently being widely applied at the population level globally.…”