BCG vaccination provides protection against IAV but not SARS-CoV-2

Kaufmann, Eva; Khan, Nargis; Tran, Kim A; Ulndreaj, Antigona; Pernet, Erwan; Fontés, Ghislaine; Lupien, Andréanne; Desmeules, Patrice; McIntosh, Fiona; Abow, Amina A.; Moorlag, Simone J.C.F.M.; Debisarun, Priya A.; Mossman, Karen; Banerjee, Arinjay; Karo‐Atar, Danielle; Sadeghi, Mina; Mubareka, Samira; Vinh, Donald C.; King, Irah L.; Robbins, Clinton S.; Behr, Marcel A.; Netea, Mihai G.; Joubert, Philippe; Divangahi, Maziar

doi:10.1016/j.celrep.2022.110502

Cited by 61 publications

(87 citation statements)

References 47 publications

(53 reference statements)

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“…We found a significant reduction of the SCV2 viral titer in BCG vaccinated animals at the peak of infection on day 4. A recent study of both intravenous and subcutaneous BCG in two species of hamsters (golden Syrian and Roborovski) found that neither route of vaccination protected either hamster species against SCV2 challenge (30). Our study differed from that of Kaufmann et al in that we used a higher dose of BCG (5×10 6 as opposed to 1×10 6 CFU), a higher viral challenge dose (5×10 5 as opposed to 1×10 5 or 1.4×10 4 PFU), and our peak disease sacrifice time was one day later (day 4) than theirs (day 3).…”

Section: Discussionmentioning

confidence: 99%

“…Two recent reports show that subcutaneous BCG does not protect in mouse models of SCV2 infection (28,29), but that intravenous BCG does confer protection in mice (29). A recent hamster study showed that both subcutaneous and intravenous BCG vaccination were ineffective in SCV2 disease prevention (30). These prior studies did not evaluate the comprehensive cellular immune landscape using robust, global immune profiling transcriptomic tools such as single cell RNA sequencing (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

“…A recent hamster study showed that both subcutaneous and intravenous BCG vaccination were ineffective in SCV2 disease prevention (30). These prior studies did not evaluate the comprehensive cellular immune landscape using robust, global immune profiling transcriptomic tools such as single cell RNA sequencing (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

“…The copyright holder for this preprint this version posted March 15, 2022. ; https://doi.org/10.1101/2022.03. 15.484018 doi: bioRxiv preprint comprehensive cellular immune landscape using robust, global immune profiling transcriptomic tools such as single cell RNA sequencing (28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

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Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation

Singh

Wang

Lombardo

et al. 2022

Preprint

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COVID-19 continues to exact a toll on human health despite the availability of several vaccines. Bacillus Calmette Guerin (BCG) has been shown to confer heterologous immune protection against viral infections including COVID-19 and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model together with immune profiling and single cell RNA sequencing (scRNAseq). We observed that BCG reduced both lung SCV2 viral load and bronchopneumonia. This was accompanied by an increase in lung alveolar macrophages, a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. Single cell transcriptome profiling showed that BCG uniquely recruits immunoglobulin-producing plasma cells to the lung suggesting accelerated antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, and differentially expressed gene (DEG) analysis showed a transcriptional shift away from exhaustion markers and towards antigen presentation and repair. Similarly, BCG enhanced lung recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, with both cell-types also showing reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation

Singh

Wang

Lombardo

et al. 2022

Preprint

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“…In studies using mice expressing the human SARS-CoV-2 receptor, administration of BCG vaccine reduced morbidity and mortality upon SARS-CoV-2 infection ( 47 , 48 ). But in studies with mice, hamsters, and rhesus macaques, BCG vaccination did not protect animals from SARS-CoV-2 infection ( 124 , 125 ). The results need to be compared in terms of animals used, study methods and administration routes, and BCG strains.…”

Section: Use Of Lavs For Control Of Newly Emerging Virusesmentioning

confidence: 98%

Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections

Seo

Seong

2022

Front. Immunol.

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Live vaccines use attenuated microbes to acquire immunity against pathogens in a safe way. As live attenuated vaccines (LAVs) still maintain infectivity, the vaccination stimulates diverse immune responses by mimicking natural infection. Induction of pathogen-specific antibodies or cell-mediated cytotoxicity provides means of specific protection, but LAV can also elicit unintended off-target effects, termed non-specific effects. Such mechanisms as short-lived genetic interference and non-specific innate immune response or long-lasting trained immunity and heterologous immunity allow LAVs to develop resistance to subsequent microbial infections. Based on their safety and potential for interference, LAVs may be considered as an alternative for immediate mitigation and control of unexpected pandemic outbreaks before pathogen-specific therapeutic and prophylactic measures are deployed.

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The impact of trained immunity in respiratory viral infections

Piret,

Boivin

2024

Reviews in Medical Virology

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Epidemic peaks of respiratory viruses that co‐circulate during the winter‐spring seasons can be synchronous or asynchronous. The occurrence of temporal patterns in epidemics caused by some respiratory viruses suggests that they could negatively interact with each other. These negative interactions may result from a programme of innate immune memory, known as trained immunity, which may confer broad protective effects against respiratory viruses. It is suggested that stimulation of innate immune cells by a vaccine or a pathogen could induce their long‐term functional reprogramming through an interplay between metabolic and epigenetic changes, which influence the transcriptional response to a secondary challenge. During the coronavirus disease 2019 pandemic, the circulation of most respiratory viruses was prevented by non‐pharmacological interventions and then resumed at unusual periods once sanitary measures were lifted. With time, respiratory viruses should find again their own ecological niches. This transition period provides an opportunity to study the interactions between respiratory viruses at the population level.

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BCG vaccination provides protection against IAV but not SARS-CoV-2

Cited by 61 publications

References 47 publications

Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation

Dynamic single-cell RNA sequencing reveals BCG vaccination curtails SARS-CoV-2 induced disease severity and lung inflammation

Prospects on Repurposing a Live Attenuated Vaccine for the Control of Unrelated Infections

The impact of trained immunity in respiratory viral infections

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