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:10.1038/s41591-023-02228-4

Cited by 52 publications

(59 citation statements)

References 27 publications

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“…Our in silico analysis agrees well with the conclusions of the recent study by Khoury et al, 10 . This study predicted that boosting with ancestral vaccines can signi cantly enhance protection against both symptomatic and severe disease caused by SARS-CoV-2 variants, but variant-modi ed vaccines offer additional protection, even if they do not perfectly match to the circulating variants.…”

Section: Full Textsupporting

confidence: 93%

In silico clinical studies for the design of optimal COVID-19 vaccination schedules in patients with cancer

Jain

Voutouri

Hardin

et al. 2023

Preprint

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As we approach an endemic phase of COVID-19, there is an urgent need for the development of novel and flexible tools to predict the effectiveness of COVID-19 vaccines over the long term. This is particularly evident for patients with significant comorbidities, such as cancer, who may be underrepresented in general vaccine cohorts. More rigorous and scientifically grounded guidelines may help reduce the now prevalent "vaccine fatigue" (Stamm et al., Nature Medicine 2023). We propose that in silico clinical studies, i.e., use of computer simulations for the evaluation of a medicinal product or intervention, is a feasible solution. We have developed a mechanistic mathematical model of SARS-CoV-2 infection to better understand the mechanisms of COVID-19, that account for the specific characteristics of novel variants, including immune evasion and replicative potential. Previously, we used this modeling framework to predict the long-term effectiveness of COVID-19 vaccines in healthy individuals and those who have cancer or suppressed immune responses and performed in silico studies to predict vaccines effectiveness (Voutouri, et al, PNAS 2023). Here we present a comparison of our model predictions with data on bivalent vaccines. Our modeling framework provides a useful tool for predicting the effectiveness of booster doses for different vaccine variants, and our findings suggest that bivalent boosters are particularly effective for patients with cancer We hope that our study will contribute to the development of effective vaccination strategies for vulnerable populations.

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Section: Full Textsupporting

confidence: 93%

In silico clinical studies for the design of optimal COVID-19 vaccination schedules in patients with cancer

Jain

Voutouri

Hardin

et al. 2023

Preprint

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“…Self-collected DBS that could be shipped by mail facilitated SARS-CoV-2 seroprevalence [25–32] and longitudinal household cohort studies [27, 33]. The binding antibody concentrations against ancestral RBD and N antigens observed using acute-phase DBS were consistent with those measured at illness onset and the convalescent phase using the Meso Scale Diagnostics quantitative binding assay utilized in many COVID-19 vaccine trials [1, 3, 5, 21]. Studies evaluating bAb from DBS and serum specimen types may provide additional tools for evaluating correlates of protection against future SARS-CoV-2 variants [2, 5, 34].…”

Section: Discussionmentioning

confidence: 92%

“…2 The Omicron-predominant period was defined as the period from December 25, 2021-June 29, 2022. 3 Wilcoxon rank sum test; Pearson's Chi-squared test; Fisher's exact test 4 Wilcoxon rank sum test; Pearson's Chi-squared test 5 3 missing sex 6 23 missing race/ethnicity 7 Evidence of prior SARS-CoV-2 infection was defined as electronic medical record documentation of prior positive SARS-CoV-2 tests or anti-N bAb levels in acute sera indicative of prior infection (≥6.9 BAU/mL). Prior infection was documented from March 17, 2020, to June 12, 2022.…”

Section: Tables Table 1 Characteristics Of Covid-19 Case and Sars-cov...mentioning

confidence: 99%

“…Immune correlates of protection following vaccination are important for immunobridging studies and potential evaluation of new COVID-19 vaccines and formulations [1, 2, 4]. Assessing protective antibody levels in the population may help not only vaccine evaluation but also prediction of susceptibility to and protection against emerging variants [5]. Immune correlates are continually re-evaluated as levels of protection mediated by antibodies vary with time and emergence of new SARS-CoV-2 variants.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021–June 2022

Sumner,

Yadav,

Noble

et al. 2023

Preprint

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Background: We assessed the association between antibody concentration within 5 days of symptom onset and COVID-19 illness among patients enrolled in a test-negative study. Methods: From October 2021 to June 2022, study sites in seven states enrolled and tested respiratory specimens from patients of all ages presenting with acute respiratory illness for SARS-CoV-2 infection using rRT-PCR. In blood specimens, we measured concentration of anti-SARS-CoV-2 antibodies against the ancestral strain spike protein receptor binding domain (RBD) and nucleocapsid (N) antigens in standardized binding antibody units (BAU/mL). Percent reduction in odds of symptomatic COVID-19 by anti-RBD antibody was estimated using logistic regression modeled as (1-adjusted odds ratio of COVID-19)x100, adjusting for COVID-19 vaccination status, age, site, and high-risk exposure. Results: A total of 662 (33%) of 2,018 symptomatic patients tested positive for acute SARS-CoV-2 infection. During the Omicron-predominant period, geometric mean anti-RBD binding antibody concentrations measured 823 BAU/mL (95% CI:690 to 981) among COVID-19 case-patients versus 1,189 BAU/mL (95% CI:1,050 to 1,347) among SARS-CoV-2 test-negative patients. In the adjusted logistic regression, increasing levels of anti-RBD antibodies were associated with reduced odds of COVID-19 for both Delta and Omicron infections. Conclusion: Higher anti-RBD antibodies in patients were associated with protection against symptomatic COVID-19 during emergence of SARS-CoV-2 Delta and Omicron variants.

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“…Here, we observed that while a 2 nd dose of mRNA COVID-19 ancestral vaccine did induce stronger overall antibody-mediated FcγR engagement in plasma and saliva, it favored responses against the imprinted ancestral wildtype spike. Receiving the bivalent or variant-based vaccines instead of the ancestral vaccine could be more effective in promoting broader cross-reactive antibodies and overcome the limitations of immune imprinting by ancestral SARS-CoV-2 spike [37, 38].…”

Section: Discussionmentioning

confidence: 99%

Lasting first impression: Pre-existing immunity restricts mucosal antibody responses during Omicron breakthrough

Selva

Ramanathan

Haycroft

et al. 2023

Preprint

Self Cite

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Understanding mucosal antibody responses from SARS-CoV-2 infection and/or vaccination is crucial to develop strategies for longer term immunity, especially against emerging viral variants. We profiled serial paired mucosal and plasma antibodies from: COVID-19 vaccinated only vaccinees (vaccinated, uninfected), COVID-19 recovered vaccinees (convalescent, vaccinated) and individuals with breakthrough Delta or Omicron BA.2 infections (vaccinated, infected). Saliva from COVID-19 recovered vaccinees displayed improved antibody neutralizing activity, FcγR engagement and IgA compared to COVID-19 uninfected vaccinees. Furthermore, repeated mRNA vaccination boosted SARS-CoV-2-specific IgG2 and IgG4 responses in both mucosa biofluids (saliva and tears) and plasma. IgG, but not IgA, responses to breakthrough COVID-19 variants were dampened and narrowed by increased pre-existing vaccine-induced immunity to the ancestral strain. Salivary antibodies delayed initiation of boosting following breakthrough COVID-19 infection, especially Omicron BA.2, however, rose rapidly thereafter. Our data highlight how pre-existing immunity shapes mucosal SARS-CoV-2-specific antibody responses and has implications for long-term protection from COVID-19.

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

Cited by 52 publications

References 27 publications

In silico clinical studies for the design of optimal COVID-19 vaccination schedules in patients with cancer

In silico clinical studies for the design of optimal COVID-19 vaccination schedules in patients with cancer

Anti-SARS-CoV-2 Antibody Levels Associated with COVID-19 Protection in Outpatients Tested for SARS-CoV-2, US Flu VE Network, October 2021–June 2022

Lasting first impression: Pre-existing immunity restricts mucosal antibody responses during Omicron breakthrough

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