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1.
J Exp Med ; 219(2)2022 02 07.
Article in English | MEDLINE | ID: covidwho-1565893

ABSTRACT

In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guérin (BCG) has been reported to confer nonspecific resistance to unrelated pulmonary pathogens, a phenomenon attributed to the induction of long-lasting alterations within the myeloid cell compartment. Here, we demonstrate that intravenous, but not subcutaneous, inoculation of BCG protects human-ACE2 transgenic mice against lethal challenge with SARS-CoV-2 (SCV2) and results in reduced viral loads in non-transgenic animals infected with an α variant. The observed increase in host resistance was associated with reductions in SCV2-induced tissue pathology, inflammatory cell recruitment, and cytokine production that multivariate analysis revealed as only partially related to diminished viral load. We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and ensuing immunopathology. While intravenous BCG vaccination is not a clinically acceptable practice, our findings provide an experimental model for identifying mechanisms by which nonspecific stimulation of the pulmonary immune response promotes host resistance to SCV2 lethality.


Subject(s)
BCG Vaccine/immunology , COVID-19/immunology , SARS-CoV-2/immunology , Administration, Intravenous , Angiotensin-Converting Enzyme 2/metabolism , Animals , Chemokines/metabolism , Humans , Inflammation/pathology , Mice, Inbred C57BL , Mice, Transgenic , Viral Load
2.
Lancet Infect Dis ; 21(11): 1590-1597, 2021 11.
Article in English | MEDLINE | ID: covidwho-1561435

ABSTRACT

BACKGROUND: Trials of BCG vaccination to prevent or reduce severity of COVID-19 are taking place in adults, some of whom have been previously vaccinated, but evidence of the beneficial, non-specific effects of BCG come largely from data on mortality in infants and young children, and from in-vitro and animal studies, after a first BCG vaccination. We assess all-cause mortality following a large BCG revaccination trial in Malawi. METHODS: The Karonga Prevention trial was a population-based, double-blind, randomised controlled in Karonga District, northern Malawi, that enrolled participants between January, 1986, and November, 1989. The trial compared BCG (Glaxo-strain) revaccination versus placebo to prevent tuberculosis and leprosy. 46 889 individuals aged 3 months to 75 years were randomly assigned to receive BCG revaccination (n=23 528) or placebo (n=23 361). Here we report mortality since vaccination as recorded during active follow-up in northern areas of the district in 1991-94, and in a demographic surveillance follow-up in the southern area in 2002-18. 7389 individuals who received BCG (n=3746) or placebo (n=3643) lived in the northern follow-up areas, and 5616 individuals who received BCG (n=2798) or placebo (n=2818) lived in the southern area. Year of death or leaving the area were recorded for those not found. We used survival analysis to estimate all-cause mortality. FINDINGS: Follow-up information was available for 3709 (99·0%) BCG recipients and 3612 (99·1%) placebo recipients in the northern areas, and 2449 (87·5%) BCG recipients and 2413 (85·6%) placebo recipients in the southern area. There was no difference in mortality between the BCG and placebo groups in either area, overall or by age group or sex. In the northern area, there were 129 deaths per 19 694 person-years at risk in the BCG group (6·6 deaths per 1000 person-years at risk [95% CI 5·5-7·8]) versus 133 deaths per 19 111 person-years at risk in the placebo group (7·0 deaths per 1000 person-years at risk [95% CI 5·9-8·2]; HR 0·94 [95% CI 0·74-1·20]; p=0·62). In the southern area, there were 241 deaths per 38 399 person-years at risk in the BCG group (6·3 deaths per 1000 person-years at risk [95% CI 5·5-7·1]) versus 230 deaths per 38 676 person-years at risk in the placebo group (5·9 deaths per 1000 person-years at risk [95% CI 5·2-6·8]; HR 1·06 [95% CI 0·88-1·27]; p=0·54). INTERPRETATION: We found little evidence of any beneficial effect of BCG revaccination on all-cause mortality. The high proportion of deaths attributable to non-infectious causes beyond infancy, and the long time interval since BCG for most deaths, might obscure any benefits. FUNDING: British Leprosy Relief Association (LEPRA); Wellcome Trust.


Subject(s)
BCG Vaccine/administration & dosage , Immunization, Secondary/statistics & numerical data , Mortality , Vaccination/methods , Adolescent , Adult , Aged , BCG Vaccine/immunology , COVID-19/epidemiology , COVID-19/immunology , COVID-19/prevention & control , Child , Child, Preschool , Double-Blind Method , Female , Follow-Up Studies , Humans , Immunogenicity, Vaccine , Leprosy/immunology , Leprosy/mortality , Leprosy/prevention & control , Malawi/epidemiology , Male , Middle Aged , Mycobacterium leprae/immunology , SARS-CoV-2/immunology , Treatment Outcome , Tuberculosis/immunology , Tuberculosis/mortality , Tuberculosis/prevention & control , Vaccination/statistics & numerical data , Young Adult
3.
Virology ; 565: 73-81, 2022 01 02.
Article in English | MEDLINE | ID: covidwho-1545481

ABSTRACT

Bacillus Calmette-Guérin (BCG) vaccine is currently used to prevent tuberculosis infection. The vaccine was found to enhance resistance to certain types of infection including positive sense RNA viruses. The current COVID-19 pandemic is caused by positive sense RNA, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A higher mortality rate of COVID-19 patients was reported in countries where BCG vaccination is not routinely administered, when compared to the vaccinated ones. We hypothesized that BCG vaccine may control SARS-CoV2 infection via modulating the monocyte immune response. We analyzed GSE104149 dataset to investigate whether human monocytes of BCG-vaccinated individuals acquire resistance to SARS-CoV-2 infection. Differentially expressed genes obtained from the dataset were used to determine enriched pathways, biological processes, and molecular functions for monocytes post BCG vaccination. Our data show that BCG vaccine promotes a more effective immune response of monocytes against SARS-CoV2, but probably not sufficient to prevent the infection.


Subject(s)
BCG Vaccine/immunology , COVID-19/epidemiology , Vaccination/statistics & numerical data , BCG Vaccine/administration & dosage , COVID-19/prevention & control , Gene Expression Profiling , Humans , Inflammation , Monocytes/immunology , Monocytes/virology , SARS-CoV-2/physiology
4.
PLoS One ; 16(11): e0258743, 2021.
Article in English | MEDLINE | ID: covidwho-1511818

ABSTRACT

BCG vaccination is known to induce innate immune memory, which confers protection against heterologous infections. However, the effect of BCG vaccination on the conventional adaptive immune cells subsets is not well characterized. We investigated the impact of BCG vaccination on the frequencies of T cell subsets and common gamma c (γc) cytokines in a group of healthy elderly individuals (age 60-80 years) at one month post vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrate that BCG vaccination induced enhanced frequencies of central (p<0.0001) and effector memory (p<0.0001) CD4+ T cells and diminished frequencies of naïve (p<0.0001), transitional memory (p<0.0001), stem cell memory (p = 0.0001) CD4+ T cells and regulatory T cells. In addition, BCG vaccination induced enhanced frequencies of central (p = 0.0008), effector (p<0.0001) and terminal effector memory (p<0.0001) CD8+ T cells and diminished frequencies of naïve (p<0.0001), transitional memory (p<0.0001) and stem cell memory (p = 0.0034) CD8+T cells. BCG vaccination also induced enhanced plasma levels of IL-7 (p<0.0001) and IL-15 (p = 0.0020) but diminished levels of IL-2 (p = 0.0033) and IL-21 (p = 0.0020). Thus, BCG vaccination was associated with enhanced memory T cell subsets as well as memory enhancing γc cytokines in elderly individuals, suggesting its ability to induce non-specific adaptive immune responses.


Subject(s)
BCG Vaccine/immunology , Cytokines/immunology , Immunologic Memory/immunology , Interleukin Receptor Common gamma Subunit/immunology , Aged , Aged, 80 and over , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Female , Humans , Interleukins/immunology , Male , Middle Aged , Mycobacterium tuberculosis/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Regulatory/immunology , Vaccination/methods
5.
Pharmazie ; 75(8): 375-380, 2020 08 01.
Article in English | MEDLINE | ID: covidwho-1435671

ABSTRACT

Diabetes mellitus (DM) is one of the major risk factors for COVID-19 complications as it is one of the chronic immune-compromising conditions especially if patients have uncontrolled diabetes, poor HbA1c and/or irregular blood glucose levels. Diabetic patients' mortality rates with COVID-19 are higher than those of cardiovascular or cancer patients. Recently, Bacillus Calmette-Guérin (BCG) vaccine has shown successful results in reversing diabetes in both rats and clinical trials based on different mechanisms from aerobic glycolysis to beta cells regeneration. BCG is a multi-face vaccine that has been used extensively in protection from tuberculosis (TB) and leprosy and has been repositioned for treatment of bladder cancer, diabetes and multiple sclerosis. Recently, COVID-19 epidemiological studies confirmed that universal BCG vaccination reduced morbidity and mortality in certain geographical areas. Countries without universal policies of BCG vaccination (Italy, Nederland, USA) have been more severely affected compared to countries with universal and long-standing BCG policies that have shown low numbers of reported COVID-19 cases. Some countries have started clinical trials that included a single dose BCG vaccine as prophylaxis from COVID-19 or an attempt to minimize its side effects. This proposed research aims to use BCG vaccine as a double-edged weapon countering both COVID-19 and diabetes, not only as protection but also as therapeutic vaccination. The work includes a case study of regenerated pancreatic beta cells based on improved C-peptide and PCPRI laboratory findings after BCG vaccination for a 9 year old patient. The patient was re-vaccinated based on a negative tuberculin test and no scar at the site of injection of the 1st BCG vaccination at birth. The authors suggest and invite the scientific community to take into consideration the concept of direct BCG re-vaccination (after 4 weeks) because of the reported gene expressions and exaggerated innate immunity consequently. As the diabetic MODY-5 patient (mutation of HNF1B, Val2Leu) was on low dose Riomet® while eliminating insulin gradually, a simple analytical method for metformin assay was recommended to ensure its concentration before use as it is not approved yet by the Egyptian QC labs.


Subject(s)
BCG Vaccine/administration & dosage , Coronavirus Infections/immunology , Diabetes Mellitus/immunology , Insulin-Secreting Cells/cytology , Pneumonia, Viral/immunology , Animals , BCG Vaccine/immunology , COVID-19 , Child , Coronavirus Infections/complications , Diabetes Mellitus/physiopathology , Humans , Male , Pandemics , Pneumonia, Viral/complications , Rats , Regeneration/immunology , Risk Factors , Vaccination/methods
6.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Article in English | MEDLINE | ID: covidwho-1387607

ABSTRACT

The global incidence of tuberculosis remains unacceptably high, with new preventative strategies needed to reduce the burden of disease. We describe here a method for the generation of synthetic self-adjuvanted protein vaccines and demonstrate application in vaccination against Mycobacterium tuberculosis Two vaccine constructs were designed, consisting of full-length ESAT6 protein fused to the TLR2-targeting adjuvants Pam2Cys-SK4 or Pam3Cys-SK4 These were produced by chemical synthesis using a peptide ligation strategy. The synthetic self-adjuvanting vaccines generated powerful local CD4+ T cell responses against ESAT6 and provided significant protection in the lungs from virulent M. tuberculosis aerosol challenge when administered to the pulmonary mucosa of mice. The flexible synthetic platform we describe, which allows incorporation of adjuvants to multiantigenic vaccines, represents a general approach that can be applied to rapidly assess vaccination strategies in preclinical models for a range of diseases, including against novel pandemic pathogens such as SARS-CoV-2.


Subject(s)
Mycobacterium tuberculosis/immunology , Tuberculosis Vaccines/pharmacology , Tuberculosis/immunology , Tuberculosis/prevention & control , Vaccines, Conjugate/pharmacology , Adjuvants, Immunologic/pharmacology , Animals , Antigens, Bacterial/immunology , BCG Vaccine/immunology , BCG Vaccine/pharmacology , Bacterial Proteins , CD4-Positive T-Lymphocytes/immunology , COVID-19/prevention & control , Disease Models, Animal , Female , Mice , Mice, Inbred C57BL , SARS-CoV-2/immunology , Toll-Like Receptor 2/immunology , Tuberculosis Vaccines/immunology , Vaccines, Conjugate/immunology , Vaccines, Synthetic/immunology , Vaccines, Synthetic/pharmacology
8.
Cell ; 181(5): 969-977, 2020 05 28.
Article in English | MEDLINE | ID: covidwho-1385208

ABSTRACT

SARS-CoV-2 infection is mild in the majority of individuals but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed "trained immunity," by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections through epigenetic, transcriptional, and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole-microorganism vaccines may represent an important tool for reducing susceptibility to and severity of SARS-CoV-2.


Subject(s)
Betacoronavirus/physiology , Coronavirus Infections/immunology , Immunity, Innate , Immunomodulation , Pneumonia, Viral/immunology , SARS Virus/physiology , Animals , BCG Vaccine/immunology , COVID-19 , Clinical Trials as Topic , Coronavirus Infections/pathology , Coronavirus Infections/physiopathology , Coronavirus Infections/transmission , Humans , Immunity, Innate/drug effects , Lung/immunology , Lung/pathology , Lymphopenia/pathology , Middle East Respiratory Syndrome Coronavirus/physiology , Pandemics , Pneumonia, Viral/pathology , Pneumonia, Viral/physiopathology , Pneumonia, Viral/transmission , SARS-CoV-2 , Severe Acute Respiratory Syndrome/immunology , Severe Acute Respiratory Syndrome/pathology , Virus Replication
9.
Front Immunol ; 12: 692729, 2021.
Article in English | MEDLINE | ID: covidwho-1369667

ABSTRACT

Epidemiological studies and clinical trials suggest Bacillus Calmette-Guérin (BCG) vaccine has protective effects against coronavirus disease 2019 (COVID-19). There are now over 30 clinical trials evaluating if BCG vaccination can prevent or reduce the severity of COVID-19. However, the mechanism by which BCG vaccination can induce severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses is unknown. Here, we identify 8 novel BCG-derived peptides with significant sequence homology to either SARS-CoV-2 NSP3 or NSP13-derived peptides. Using an in vitro co-culture system, we show that human CD4+ and CD8+ T cells primed with a BCG-derived peptide developed enhanced reactivity to its corresponding homologous SARS-CoV-2-derived peptide. As expected, HLA differences between individuals meant that not all persons developed immunogenic responses to all 8 BCG-derived peptides. Nevertheless, all of the 20 individuals that were primed with BCG-derived peptides developed enhanced T cell reactivity to at least 7 of 8 SARS-CoV-2-derived peptides. These findings provide an in vitro mechanism that may account, in part, for the epidemiologic observation that BCG vaccination confers some protection from COVID-19.


Subject(s)
BCG Vaccine/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cross Reactions , SARS-CoV-2/immunology , Adult , COVID-19/immunology , COVID-19/prevention & control , Cells, Cultured , Coculture Techniques , Female , Flow Cytometry , Humans , Male , Sequence Analysis, Protein , Sequence Homology , Vaccines, Subunit/immunology , Young Adult
10.
Sci Adv ; 7(32)2021 08.
Article in English | MEDLINE | ID: covidwho-1343935

ABSTRACT

We investigated the influence of Bacillus Calmette-Guérin (BCG) vaccination on the unstimulated plasma levels of a wide panel of cytokines, chemokines, acute-phase proteins (APPs), matrix metalloproteinases (MMPs), and growth factors in a group of healthy elderly individuals (age, 60 to 80 years) at baseline (before vaccination) and 1 month after vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrated that BCG vaccination resulted in diminished plasma levels of types 1, 2, and 17 and other proinflammatory cytokines and type 1 interferons. BCG vaccination also resulted in decreased plasma levels of CC, CXC chemokines, APPs, MMPs, and growth factors. Plasma levels of the aforementioned parameters were significantly lower in vaccinated individuals when compared to unvaccinated control individuals. Thus, our study demonstrates the immunomodulatory properties of BCG vaccination and suggests its potential utility in nonspecific vaccination of COVID-19 by down-modulating pathogenic inflammatory responses.


Subject(s)
BCG Vaccine/administration & dosage , COVID-19/immunology , Cytokines/metabolism , Inflammation Mediators/metabolism , Inflammation/prevention & control , Vaccination/methods , Aged , Aged, 80 and over , BCG Vaccine/immunology , COVID-19/epidemiology , COVID-19/virology , Case-Control Studies , Female , Humans , India/epidemiology , Inflammation/immunology , Inflammation/metabolism , Inflammation/pathology , Male , Middle Aged , SARS-CoV-2/immunology
11.
Viral Immunol ; 34(5): 300-306, 2021 06.
Article in English | MEDLINE | ID: covidwho-1343606

ABSTRACT

Coronavirus disease 2019 (COVID-19) has become a global pandemic in 2020. The pathogen responsible for the COVID-19 has been found to be coronavirus (2019-nCoV) with human transmission through droplets, airway secretions, and even direct contact with host. Currently multiple drugs and their combinations are being tried for the treatment of the COVID-19 disease, but none approved. In absence of definitive and approved treatment, it is imperative that prevention of COVID-19 infection is of utmost importance. For the same, face masks, hand hygiene, isolation, and quarantine are being practiced all over the world. However much successful these methods be, they cannot be used for a very long time. Thus, it becomes necessary that a vaccine be developed for the disease so that the further spread could be halted. Some reports suggest the use of Bacillus Calmette-Guerin (BCG) vaccine as the prophylaxis for coronavirus. BCG vaccine is a live attenuated vaccine, used for prophylaxis of Mycobacterium tuberculosis and is present in the essential list of the World Health Organization as well as immunization programs of many countries. Immunostimulatory antiviral effects of BCG vaccine are well known. At present, there are no published evidence available to support the use of BCG vaccine for the prevention of coronavirus infection. However, there have been speculations on enhanced immunity with BCG vaccine, which might be useful in prevention of coronavirus infection. Results from the clinical studies of BCG vaccine in vulnerable population are required to confirm this hypothesis.


Subject(s)
BCG Vaccine/administration & dosage , BCG Vaccine/immunology , COVID-19/immunology , COVID-19/prevention & control , Humans , Immunity, Innate , Vaccination
12.
Expert Rev Vaccines ; 20(9): 1051-1057, 2021 09.
Article in English | MEDLINE | ID: covidwho-1327291

ABSTRACT

INTRODUCTION: The COVID-19 pandemic is a globalized health concern caused by a beta-coronavirus named Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Since December 2019, when this outbreak flared in Wuhan, China, COVID-19 cases have been continuously rising all over the world. Due to the emergence of SARS-CoV-2 mutants, subsequent waves are flowing in a faster manner as compared to the primary wave, which is more contagious and causing higher mortality. Recently, India has emerged as the new epicenter of the second wave by mutants of SARS-CoV-2. After almost eighteen months of this outbreak, some COVID-19 dedicated therapeutics and vaccines are available, and a few are under trial, but the situation is still uncontrolled. AREA COVERED: This perspective article covers the repurposing of childhood vaccines like Bacille Calmette-Guerin (BCG), Measles, Mumps, Rubella (MMR), and Oral Polio Vaccine (OPV), which are live attenuated vaccines and have been shown the protective effect through 'trained immunity and 'crossreactivity.' EXPERT OPINION: This perspective article has suggested that combinatorial use of these childhood vaccines might exert a better protective effect along with the available COVID-19 therapeutic and vaccines which could be considered as a preventive option against SARS-CoV-2 infection as well as its subsequent waves.


Subject(s)
BCG Vaccine/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Drug Repositioning/methods , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology , Cross Reactions/immunology , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Humans , Immunity, Innate/drug effects , Immunity, Innate/immunology , Measles-Mumps-Rubella Vaccine/immunology , Poliovirus Vaccine, Oral/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination , Yellow Fever Vaccine/immunology
13.
Clin Dermatol ; 39(1): 98-103, 2021.
Article in English | MEDLINE | ID: covidwho-1300696

ABSTRACT

The Bacillus Calmette-Guérin (BCG) vaccine has been used since 1921 initially for protection against tuberculosis. BCG acts through stimulation of cell-mediated adaptive immunity with activation of the Th1 cells and production of interferon gamma. Additionally, it is able to stimulate the immune system in a nonspecific manner, which results in effectiveness of the BCG against non-mycobacterial infections and in some malignant, autoimmune, and inflammatory diseases. Recently, its potential use in the fight against the coronavirus disease 2019 (COVID-19) pandemic has been suggested. This is based upon the concept of BCG-induced trained innate immunity-a memory-like response of the innate immune system that can realize greater protection in case of re-infection. This hypothesis represents a milestone in the potential use of the BCG vaccine in the fight with the novel coronavirus.


Subject(s)
Adjuvants, Immunologic , BCG Vaccine/immunology , COVID-19/prevention & control , COVID-19/mortality , Humans , Immunity, Innate , SARS-CoV-2
15.
PLoS One ; 16(6): e0253169, 2021.
Article in English | MEDLINE | ID: covidwho-1278188

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created a remarkable and varying impact in every country, inciting calls for broad attention. Recently, the Bacillus Calmette-Guérin (BCG) vaccination has been regarded as a potential candidate to explain this difference. Herein, we hypothesised that the past epidemic of Mycobacterium tuberculosis (M. tuberculosis) may act as a latent explanatory factor for the worldwide differences seen in COVID-19 impact on mortality and incidence. We compared two indicators of past epidemic of M. tuberculosis, specifically, incidence (90 countries in 1990) and mortality (28 countries in 1950), with the mortality and incidence of COVID-19. We determined that an inverse relationship existed between the past epidemic indicators of M. tuberculosis and current COVID-19 impact. The rate ratio of the cumulative COVID-19 mortality per 1 million was 2.70 (95% confidence interval [CI]: 1.09-6.68) per 1 unit decrease in the incidence rate of tuberculosis (per 100,000 people). The rate ratio of the cumulative COVID-19 incidence per 1 million was 2.07 (95% CI: 1.30-3.30). This association existed even after adjusting for potential confounders (rate of people aged 65 over, diabetes prevalence, the mortality rate from cardiovascular disease, and gross domestic product per capita), leading to an adjusted rate ratio of COVID-19 mortality of 2.44, (95% CI: 1.32-4.52) and a COVID-19 incidence of 1.31 (95% CI: 0.97-1.78). After latent infection, Mycobacterium survives in the human body and may continue to stimulate trained immunity. This study suggests a possible mechanism underlying the region-based variation in the COVID-19 impact.


Subject(s)
BCG Vaccine/immunology , COVID-19/prevention & control , Mycobacterium tuberculosis/immunology , SARS-CoV-2/isolation & purification , Tuberculosis/immunology , COVID-19/epidemiology , COVID-19/virology , Epidemics , Humans , Incidence , Models, Theoretical , Mycobacterium tuberculosis/physiology , Prevalence , SARS-CoV-2/physiology , Survival Rate , Tuberculosis/epidemiology , Tuberculosis/microbiology , Vaccination
16.
Int Immunopharmacol ; 96: 107763, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1258391

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the rapidly spreading pandemic COVID-19 in the world. As an effective therapeutic strategy is not introduced yet and the rapid genetic variations in the virus, there is an emerging necessity to design, evaluate and apply effective new vaccines. An acceptable vaccine must elicit both humoral and cellular immune responses, must have the least side effects and the storage and transport systems should be available and affordable for all countries. These vaccines can be classified into different types: inactivated vaccines, live-attenuated virus vaccines, subunit vaccines, virus-like particles (VLPs), nucleic acid-based vaccines (DNA and RNA) and recombinant vector-based vaccines (replicating and non-replicating viral vector). According to the latest update of the WHO report on April 2nd, 2021, at least 85 vaccine candidates were being studied in clinical trial phases and 184 candidate vaccines were being evaluated in pre-clinical stages. In addition, studies have shown that other vaccines, including the Bacillus Calmette-Guérin (BCG) vaccine and the Plant-derived vaccine, may play a role in controlling pandemic COVID-19. Herein, we reviewed the different types of COVID-19 candidate vaccines that are currently being evaluated in preclinical and clinical trial phases along with advantages, disadvantages or adverse reactions, if any.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , BCG Vaccine/immunology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Drug Evaluation, Preclinical , Female , Humans , Male , Meta-Analysis as Topic , Middle Aged , Vaccines, DNA/immunology , Vaccines, Inactivated/immunology , Vaccines, Subunit/immunology , Vaccines, Virus-Like Particle/immunology , Viral Vaccines/immunology
17.
Expert Rev Vaccines ; 20(7): 857-880, 2021 07.
Article in English | MEDLINE | ID: covidwho-1254221

ABSTRACT

Introduction: The coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide and vaccination remains the most effective approach to control COVID-19. Currently, at least ten COVID-19 vaccines have been authorized under emergency authorization. However, these vaccines still face many challenges.Areas covered: This study reviews the concept and mechanisms of trained immunity induced by the Bacille Calmette Guérin (BCG) vaccine and identifies questions that should be answered before the BCG vaccine could be used to combat COVID-19 pandemic. Moreover, we present for the first time the details of current BCG vaccine clinical trials, which are underway in various countries, to assess its effectiveness in combating the COVID-19 pandemic. Finally, we discuss the challenges of COVID-19 vaccines and opportunities for the BCG vaccine. The literature was found by searching the PubMed (https://pubmed.ncbi.nlm.nih.gov/), Web of Science (www.webofknowledge.com), Embase (https://www.embase.com), and CNKI (https://www.cnki.net/) databases. The date was set as the default parameter for each database.Expert opinion: The advantages of the BCG vaccine can compensate for the shortcomings of other COVID-19 vaccines. If the efficacy of the BCG vaccine against COVID-19 is confirmed by these clinical trials, the BCG vaccine may be essential to resolve the challenges faced by COVID-19 vaccines.


Subject(s)
BCG Vaccine/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , COVID-19/prevention & control , Clinical Trials as Topic/methods , Immunity, Innate/immunology , Adjuvants, Immunologic/administration & dosage , BCG Vaccine/administration & dosage , COVID-19 Vaccines/administration & dosage , Humans , Immunity, Innate/drug effects , Pandemics
18.
Mol Med ; 27(1): 54, 2021 05 31.
Article in English | MEDLINE | ID: covidwho-1249543

ABSTRACT

While vaccines traditionally have been designed and used for protection against infection or disease caused by one specific pathogen, there are known off-target effects from vaccines that can impact infection from unrelated pathogens. The best-known non-specific effects from an unrelated or heterologous vaccine are from the use of the Bacillus Calmette-Guérin (BCG) vaccine, mediated partly through trained immunity. Other vaccines have similar heterologous effects. This review covers molecular mechanisms behind the heterologous effects, and the potential use of heterologous vaccination in the current COVID-19 pandemic. We then discuss novel pandemic response strategies based on rapidly deployed, widespread heterologous vaccination to boost population-level immunity for initial, partial protection against infection and/or clinical disease, while specific vaccines are developed.


Subject(s)
BCG Vaccine/immunology , COVID-19/prevention & control , Pandemics , Vaccines/immunology , BCG Vaccine/therapeutic use , COVID-19/immunology , COVID-19/virology , Humans , Immunity, Heterologous/immunology , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Vaccines/therapeutic use
19.
Asian Pac J Allergy Immunol ; 38(3): 150-161, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-1231595

ABSTRACT

SARS-CoV-2 had already killed more than 400,000 patients around the world according to data on 7 June 2020. Bacillus Calmette-Guérin (BCG) vaccine is developed from live-attenuated Mycobacterium bovis, which is a microorganism found in a cow. Discovered by Dr. Albert Calmette and Camille Guérin since 1921, the BCG has served as a protection against tuberculosis and its complications. It is noticeable that countries which use mandatory BCG vaccination approach had lower COVID-19 infection and death rate. Current review aims to clarify this issue through epidemiological illustration of correlation between national BCG immunization and COVID-19 mortality, in addition to biological background of BCG-induced immunity Epidemiological data shows that universal BCG policy countries have lower median mortality rate compare to countries with past universal BCG policy and non-mass immunization BCG. (18 May 2020). Still, the links between BCG vaccination and better COVID-19 situation in certain countries are unclear, and more data on actual infection rate using SAR-CoV-2 antibody testing in large population sample is crucial for disease spreading comparison. Two immunological mechanisms, heterologous effects of adaptive immunity and trained innate immunity which induced by BCG vaccination, may explain host tolerance against COVID-19 infection, however, there is no direct evidence to support this biological background. Clinical trials related to BCG vaccination against COVID-19 are under investigation. Without a strong evidence, BCG must not be recommended for COVID-19 prevention, although, this should not be absolute contraindication. Risk of local and systemic complications from the vaccine should be informed to individual, who request BCG immunization.


Subject(s)
BCG Vaccine/administration & dosage , Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Vaccination , Viral Vaccines/administration & dosage , Adaptive Immunity , BCG Vaccine/adverse effects , BCG Vaccine/immunology , COVID-19 , COVID-19 Vaccines , Cause of Death , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Host-Pathogen Interactions , Humans , Immunity, Innate , Pneumonia, Viral/immunology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome , Vaccination/adverse effects , Viral Vaccines/adverse effects , Viral Vaccines/immunology
20.
Immunol Rev ; 301(1): 98-121, 2021 05.
Article in English | MEDLINE | ID: covidwho-1218116

ABSTRACT

BCG turns 100 this year and while it might not be the perfect vaccine, it has certainly contributed significantly towards eradication and prevention of spread of tuberculosis (TB). The search for newer and better vaccines for TB is an ongoing endeavor and latest results from trials of candidate TB vaccines such as M72AS01 look promising. However, recent encouraging data from BCG revaccination trials in adults combined with studies on mucosal and intravenous routes of BCG vaccination in non-human primate models have renewed interest in BCG for TB prevention. In addition, several well-demonstrated non-specific effects of BCG, for example, prevention of viral and respiratory infections, give BCG an added advantage. Also, BCG vaccination is currently being widely tested in human clinical trials to determine whether it protects against SARS-CoV-2 infection and/or death with detailed analyses and outcomes from several ongoing trials across the world awaited. Through this review, we attempt to bring together information on various aspects of the BCG-induced immune response, its efficacy in TB control, comparison with other candidate TB vaccines and strategies to improve its efficiency including revaccination and alternate routes of administration. Finally, we discuss the future relevance of BCG use especially in light of its several heterologous benefits.


Subject(s)
BCG Vaccine/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis/immunology , Tuberculosis/prevention & control , Vaccination , Adaptive Immunity , BCG Vaccine/administration & dosage , Humans , Immunity, Heterologous , Immunity, Innate , Immunogenicity, Vaccine , Immunologic Memory
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