Predicting the efficacy of variant-modified COVID-19 vaccine boosters

Khoury, David S.; Docken, Steffen S.; Subbarao, Kanta; Kent, Stephen J.; Davenport, Miles P.; Cromer, Deborah

doi:10.1101/2022.08.25.22279237

Cited by 25 publications

(18 citation statements)

References 13 publications

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“…In comparison, animals that received a primary mRNA-1273 series, and were boosted with PBS, showed rather marginal protection against lung infection. These results showing protective benefit of matched bivalent vaccine boosters targeting Omicron variants are consistent with studies in mice immunized with mRNA-1273, boosted with a monovalent mRNA-1273.529 vaccine, and challenged with BA.1 12 , and predictive models in humans 30 .…”

Section: Discussionsupporting

confidence: 87%

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

Scheaffer

Lee

Whitener

et al. 2022

Preprint

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The emergence of SARS-CoV-2 variants in the Omicron lineage with large number of substitutions in the spike protein that can evade antibody neutralization has resulted in diminished vaccine efficacy and persistent transmission. One strategy to broaden vaccine-induced immunity is to administer bivalent vaccines that encode for spike proteins from both historical and newly-emerged variant strains. Here, we evaluated the immunogenicity and protective efficacy of two bivalent vaccines that recently were authorized for use in Europe and the United States and contain two mRNAs encoding Wuhan-1 and either BA.1 (mRNA-1273.214) or BA.4/5 (mRNA-1273.222) spike proteins. As a primary immunization series in BALB/c mice, both bivalent vaccines induced broader neutralizing antibody responses than the constituent monovalent vaccines (mRNA-1273 [Wuhan-1], mRNA-1273.529 [BA.1], and mRNA-1273-045 [BA.4/5]). When administered to K18-hACE2 transgenic mice as a booster at 7 months after the primary vaccination series with mRNA-1273, the bivalent vaccines induced greater breadth and magnitude of neutralizing antibodies compared to an mRNA-1273 booster. Moreover, the response in bivalent vaccine-boosted mice was associated with increased protection against BA.5 infection and inflammation in the lung. Thus, boosting with bivalent Omicron-based mRNA-1273.214 or mRNA-1273.222 vaccines enhances immunogenicity and protection against currently circulating SARS-CoV-2 strains.

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Section: Discussionsupporting

confidence: 87%

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

Scheaffer

Lee

Whitener

et al. 2022

Preprint

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“…(period-specific SUARs). Multiple immunological, epidemiological and/or modeling studies have reinforced the improved protection afforded by hybrid (vaccine + infection) immunity over that induced by either exposure alone [32][33][34][35][36][37][38][39][40][41][42][43][44][45]. In general, booster doses using ancestral Wuhan-like antigen among previously-infected individuals have resulted in transient increased protection with marginal incremental improvement against severe outcomes.…”

Section: Suarsmentioning

confidence: 99%

Serial cross-sectional estimation of vaccine and infection-induced SARS-CoV-2 sero-prevalence in children and adults, British Columbia, Canada: March 2020 to August 2022

Skowronski

Kaweski

Irvine

et al. 2022

Preprint

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Background: We chronicle SARS-CoV-2 sero-prevalence through eight cross-sectional sero-surveys (snapshots) in the Lower Mainland (Greater Vancouver and Fraser Valley), British Columbia, Canada from March 2020 to August 2022. Methods: Anonymized-residual sera were obtained from children and adults attending an outpatient laboratory network. Sera were tested with at least three immuno-assays per snapshot to detect spike (S1) and/or nucleocapsid protein (NP) antibodies. Sero-prevalence was defined by dual-assay positivity, including any or infection-induced, the latter requiring S1+NP antibody detection from January 2021 owing to vaccine availability. Infection-induced estimates were used to assess the extent to which surveillance case reports under-estimated infections. Results: Sero-prevalence was ≤1% by the 3rd snapshot in September 2020 and <5% by January 2021 (4th). Following vaccine roll-out, sero-prevalence increased to >55% by May/June 2021 (5th), ~80% by September/October 2021 (6th), and >95% by March 2022 (7th). In all age groups, infection-induced sero-prevalence remained <15% through September/October 2021, increasing through subsequent Omicron waves to ~40% by March 2022 (7th) and ~60% by July/August 2022 (8th). By August 2022, at least 70-80% of children ≤19 years, 60-70% of adults 20-59 years, but ~40% of adults ≥60 years had been infected. Surveillance case reports under-estimated infections by 12-fold between the 6th-7th and 92-fold between the 7th-8th snapshots. Interpretation: By August 2022, most children and adults had acquired SARS-CoV-2 vaccine and infection exposures, resulting in more robust hybrid immunity. Conversely the elderly, still at greatest risk of severe outcomes, remain largely-dependent on vaccine-induced protection alone, and should be prioritized for additional doses.

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“…These ratio increases in VE are supported by preliminary serologic data for bivalent ancestral- and Omicron-targeted vaccines, compared to ancestral-targeted vaccine only. 25 Our model also includes the same waning of protection over time for first- and next-generation vaccines, and a 50% higher unit cost for multivalent vaccines compared to both first-generation and Omicron-targeted vaccines. Whilst these seem reasonable assumptions at the time of writing, it will be important to revise these assumptions as with updated estimates of expected VE and waning (e.g., based on in vitro antibody titers 26,27 or, ideally, real-world VE studies) and updated costs.…”

Section: Discussionmentioning

confidence: 99%

Epidemiologic and economic modelling of optimal COVID-19 policy: public health and social measures, masks and vaccines in Victoria, Australia

Szanyi

Wilson

Howe

et al. 2022

Preprint

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Background Identifying optimal COVID-19 policies is challenging. For Victoria, Australia (6.6 million people), we ranked 44 policy packages (two levels of stringency of public health and social measures [PHSMs]; providing respirators during infection surges; 11 vaccination schedules of current and next-generation vaccines) in the context of 64 future SARS-CoV-2 variants (combinations of transmissibility, virulence, immune escape, and incursion date). Methods We used an agent-based model to estimate morbidity, mortality, and costs over 18 months from 1 April 2022 for each scenario. Policies were ranked on cost-effectiveness (health system only and health system plus GDP perspectives), deaths and days exceeding hospital occupancy thresholds. Findings The median number of infections across the 44 policies was 6.2 million (range 5.4 to 7.1 million). Higher stringency PHSMs ranked better from a health system perspective, but not a health system plus GDP perspective. The provision of respirators to replace surgical/cloth masks had minimal impact. Vaccinating all ages was superior to nil further vaccination and targeted vaccination of individuals aged ≥60 years. Averaging over 64 future SARS-CoV-2 variant scenarios the optimal policy was a multivalent vaccine for all age groups with higher stringency PHSMs and no respirator provision. For the SARS-CoV-2 variant scenario approximating recent BA.4/5, Omicron-targeted vaccines were more likely optimal even with a three-month delay compared to boosting with current-generation vaccines. Interpretation Modelling that accommodates future scenarios with uncertainty, and that can be rapidly updated as new data arises, can provide a framework for pandemic decision making.

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Predicting the efficacy of variant-modified COVID-19 vaccine boosters

Cited by 25 publications

References 13 publications

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

Serial cross-sectional estimation of vaccine and infection-induced SARS-CoV-2 sero-prevalence in children and adults, British Columbia, Canada: March 2020 to August 2022

Epidemiologic and economic modelling of optimal COVID-19 policy: public health and social measures, masks and vaccines in Victoria, Australia

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