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Considering indirect benefits is critical when evaluating SARS-CoV-2 vaccine candidates.

ABSTRACT: Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-19 deaths. To illustrate this point, we show through simulation that a vaccine with strong indirect effects has the potential to reduce SARS-CoV-2 circulation and COVID-19 deaths to a greater extent than an alternative vaccine with stronger direct effects but weaker indirect effects. Protection via indirect effects may be of particular importance in the context of this virus, because elderly individuals are at an elevated risk of death but are also less likely to be directly protected by vaccination due to immune senescence. We therefore encourage ongoing data collection and model development aimed at evaluating the indirect effects of forthcoming SARS-CoV-2 vaccines.

SUBMITTER: Gallagher ME

PROVIDER: S-EPMC7430602 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Considering indirect benefits is critical when evaluating SARS-CoV-2 vaccine candidates.

Gallagher Molly E ME Sieben Andrew J AJ Nelson Kristin N KN Kraay Alicia N M ANM Lopman Ben B Handel Andreas A Koelle Katia K

medRxiv : the preprint server for health sciences 20200811

Significant progress has already been made in development and testing of SARS-CoV-2 vaccines, and Phase III clinical trials have begun for 6 novel vaccine candidates to date. These Phase III trials seek to demonstrate direct benefits of a vaccine on vaccine recipients. However, vaccination is also known to bring about indirect benefits to a population through the reduction of virus circulation. The indirect effects of SARS-CoV-2 vaccination can play a key role in reducing case counts and COVID-1 ...[more]

PMID: 32817958

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Project description:In the current scenario, in which an elevated number of COVID-19 survivors present with severe physical deconditioning, exercise intolerance, persistent symptoms, and other post-acute consequences, effective rehabilitation strategies are of utmost relevance. In this study, we report for the first time the effect of home-based exercise training (HBET) in a survivor patient from critical COVID-19 illness. A 67-year-old woman who had critical COVID-19 disease [71 days of hospitalization, of which 49 days were in the intensive care unit (ICU) with invasive mechanical ventilation due to respiratory failure] underwent a 10-week HBET aiming to recovering overall physical condition. Before and after the intervention, we assessed cardiopulmonary parameters, skeletal muscle strength and functionality, fatigue severity, and self-reported persistent symptoms. At baseline (3 months after discharge), she presented with severe impairment in cardiorespiratory functional capacity (<50% age predicted VO2peak). After the intervention, remarkable improvements in VO2peak (from 10.61 to 15.48 mL·kg-1·min-1, Δ: 45.9%), oxygen uptake efficiency slope (OUES; from 1.0 to 1.3 L·min-1, Δ: 30.1%), HR/VO2 slope (from 92 to 52 bpm·L-1, Δ: -43.5%), the lowest VE/VCO2 ratio (from 35.4 to 32.9 L·min-1, Δ: -7.1%), and exertional dyspnea were observed. In addition, handgrip strength (from 22 to 27 kg, Δ: 22.7%), 30-s Sit-to-Stand (30-STS; from 14 to 16 repetitions, Δ:14.3%), Timed-Up-and-Go (TUG; from 8.25 to 7.01 s, Δ: -15%) performance and post-COVID functional status (PCFS) score (from 4 to 2) were also improved from baseline to post-intervention. Self-reported persistent symptoms were also improved, and Fatigue Severity Scale (FSS) score decreased (from 4 to 2.7) from baseline to post-intervention. This is the first evidence that a semi-supervised, HBET program may be safe and potentially effective in improving cardiorespiratory and physical functionality in COVID-19 survivors. Controlled studies are warranted to confirm these findings.

Project description:Background:The present pandemic COVID-19 is caused by SARS-CoV-2, a single-stranded positive-sense RNA virus from the Coronaviridae family. Due to a lack of antiviral drugs, vaccines against the virus are urgently required. Methods:In this study, validated computational approaches were used to identify peptide-based epitopes from six structural proteins having antigenic properties. The Net-CTL 1.2 tool was used for the prediction of CD8+ T-cell epitopes, while the robust tools Bepi-Pred 2 and LBtope was employed for the identification of linear B-cell epitopes. Docking studies of the identified epitopes were performed using HADDOCK 2.4 and the structures were visualized by Discovery Studio and LigPlot+. Antigenicity, immunogenicity, conservancy, population coverage and allergenicity of the predicted epitopes were determined by the bioinformatics tools like VaxiJen v2.0 server, the Immune Epitope Database tools and AllerTOP v.2.0, AllergenFP 1.0 and ElliPro. Results:The predicted T cell and linear B-cell epitopes were considered as prime vaccine targets in case they passed the requisite parameters like antigenicity, immunogenicity, conservancy, non-allergenicity and broad range of population coverage. Among the predicted CD8+ T cell epitopes, potential vaccine targets from surface glycoprotein were; YQPYRVVVL, PYRVVVLSF, GVYFASTEK, QLTPTWRVY, and those from ORF3a protein were LKKRWQLAL, HVTFFIYNK. Similarly, RFLYIIKLI, LTWICLLQF from membrane protein and three epitopes viz; SPRWYFYYL, TWLTYTGAI, KTFPPTEPK from nucleocapsid phosphoprotein were the superior vaccine targets observed in our study. The negative values of HADDOCK and Z scores obtained for the best cluster indicated the potential of the epitopes as suitable vaccine candidates. Analysis of the 3D and 2D interaction diagrams of best cluster produced by HADDOCK 2.4 displayed the binding interaction of leading T cell epitopes within the MHC-1 peptide binding clefts. On the other hand, among linear B cell epitopes the majority of potential vaccine targets were from nucleocapsid protein, viz; 59-HGKEDLKFPRGQGVPINTNSSPDDQIGYYRRATRRIRGGDGKMKDLS-105, 227-LNQLE SKMSGKGQQQQGQTVTKKSAAEASKKPRQKRTATK-266, 3-DNGPQNQRNAPRITFGGP-20, 29-GERSGARSKQRRPQGL-45. Two other prime vaccine targets, 370-NSASFSTFKCYGVSPTKLNDLCFTNV-395 and 260-AGAAAYYVGYLQPRT-274 were identified in the spike protein. The potential B-cell conformational epitopes were predicted on the basis of a higher protrusion index indicating greater solvent accessibility. These conformational epitopes were of various lengths and belonged to spike, ORF3a, membrane and nucleocapsid proteins. Conclusions:Taken together, eleven T cell epitopes, seven B cell linear epitopes and ten B cell conformational epitopes were identified from five structural proteins of SARS-CoV-2 using advanced computational tools. These potential vaccine candidates may provide important timely directives for an effective vaccine against SARS-CoV-2.

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Considering indirect benefits is critical when evaluating SARS-CoV-2 vaccine candidates.

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Considering indirect benefits is critical when evaluating SARS-CoV-2 vaccine candidates.

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