Non-specific effect of Bacille Calmette-Guérin vaccine on the immune response to routine immunisations

doi:10.1016/j.vaccine.2013.03.059

Vaccine

Volume 31, Issue 30, 26 June 2013, Pages 3098-3103

https://doi.org/10.1016/j.vaccine.2013.03.059 Get rights and content

Highlights

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Epidemiological data show BCG decreases infant mortality from diseases other than TB.
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That BCG has non-specific immunological effects is well recognised.
•
We compared infants BCG-immunised at birth with non-BCG-immunised infants.
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We measured antibody levels following pneumococcal, Hib, tetanus and hepatitis B immunisation.
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BCG immunisation at birth influenced the subsequent antibody response to routine immunisations.

Abstract

Bacille Calmette-Guérin (BCG) is one of the most commonly administered vaccines worldwide. In addition to protection against tuberculosis (TB), evidence suggests that BCG immunisation has a number of additional beneficial non-specific immunological effects. These include a reduction in overall infant and child mortality attributable to causes other than TB in high-mortality regions. The antibody response to immunisations provides an opportunity to investigate the influence of BCG on the immune response to unrelated antigens. This study compared the antibody response to routine immunisations in BCG-immunised and non-BCG-immunised infants.

BCG-immunised infants were recruited from a related study in which BCG was given at birth and non-BCG-immunised infants were recruited from immunisation clinics. All infants received their routine immunisations according to the Australian National Immunisation Program. Concentrations of antibodies against pneumococcal (anti-Pn Ps), Haemophilus influenzae type B (anti-Hib), tetanus toxoid (anti-TT) and hepatitis B surface (anti-HBs) antigen were measured four weeks after the last (six month) set of infant immunisations.

A total of 127 parents agreed for their infants to take part in the study of which 108 were included in the final analysis (56 BCG-immunised and 52 non-BCG-immunised). The geometric mean concentration (GMC) of anti-Pn Ps IgG for all serotypes, anti-Hib IgG and anti-TT IgG were higher in the BCG-immunised group than the non-BCG-immunised group. This difference reached statistical significance for serotype 9V (p < 0.01) and 18C (p = 0.04). The GMC of anti-HBs IgG was lower in the BCG-immunised group than the non-BCG-immunised group (p = 0.03). The majority of participants in both groups had antibody levels above the protective threshold.

BCG immunisation at birth influences the antibody response to routine immunisations administered later in infancy. This has important implications for the introduction of both pneumococcal conjugate and novel TB vaccines in resource-limited countries.

Section snippets

Background

Bacille Calmette-Guérin (BCG) is one of the most commonly administered vaccines worldwide. In addition to protection against tuberculosis (TB) [1], [2], [3] and other mycobacterial infections [4], [5], BCG has a number of other beneficial non-specific immunological effects [6]. For example, intravesical BCG has been used successfully in the treatment of bladder cancer for more than 30 years [7], [8]. In addition, BCG immunisation has been implicated in the prevention of other tumours including

Study design and population

This study was a prospective, non-randomised study in Melbourne, Australia. Infants who were BCG-immunised at birth were recruited between February 2009 and October 2009 from a related but separate study [37]. Non-BCG-immunised infants were recruited between January 2010 and June 2011 from immunisation clinics. Informed consent was obtained from participants’ parents or guardians and the study was approved by the Human Research Ethics Committees of The Mercy Health Hospital for Women (R07/16)

Results

Of 68 BCG-immunised infants recruited to the study, 63 returned one month after their scheduled ‘six month’ routine immunisations. Seven were subsequently excluded for the following reasons: BCG-immunised at two months of age rather than at birth (3), not completed scheduled ‘six month’ routine immunisations (1), completed scheduled ‘six month’ routine immunisations more than one month prior (1), and failed blood collection (2). Results from 56 BCG-immunised participants were therefore included

Discussion

To date, only few studies have investigated the influence of BCG immunisation on the immune response to unrelated immunisations [40], [41], [42], [43], [44]. These have varied in the vaccine antigens included and the timing of measurement of the antibody response, and only one [40] included a non-BCG-immunised control group. Our study is the first to include the antibody response to pneumococcal and H. influenzae type b vaccines. It is also the first to compare the antibody response in

Acknowledgements

HbO-HA antigen was obtained through the NIH Biodefense and Emerging Infections Research Repository, NIAID, NIH: Haemophilus influenzae type b oligosaccharide-human serum albumin conjugate (HbO-HA Antigen), NR-12268.

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The innate immune system can display heterologous memory-like responses termed trained immunity after stimulation by certain vaccinations or infections. In this randomized, placebo-controlled trial, we investigated the modulation of Bacille Calmette-Guérin (BCG)-induced trained immunity by BCG revaccination or high-dose BCG administration, in comparison to a standard dose. We show that monocytes from all groups of BCG-vaccinated individuals exerted increased TNFα production after ex-vivo stimulation with various unrelated pathogens. Similarly, we observed increased amounts of T-cell-derived IFNγ after M. tuberculosis exposure, regardless of the BCG intervention. NK cell cytokine production, especially after heterologous stimulation with the fungal pathogen Candida albicans, was predominantly boosted after high dose BCG administration. Cytokine production capacity before vaccination was inversely correlated with trained immunity. While the induction of a trained immunity profile is largely dose- or frequency independent, baseline cytokine production capacity is associated with the magnitude of the innate immune memory response after BCG vaccination.
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Citation Excerpt :
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The emergence of coronavirus disease 2019 (COVID-19) pandemic in Wuhan city, China at the end of 2019 made it urgent to identify the origin of the causal pathogen and its molecular evolution, to appropriately design an effective vaccine. This study analyzes the evolutionary background of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or SARS-2) in accordance with its close relative SARS-CoV (SARS-1), which was emerged in 2002. A comparative genomic and proteomic study was conducted on SARS-2, SARS-1, and Middle East respiratory syndrome coronavirus (MERS), which was emerged in 2012. In silico analysis inferred the genetic variability among the tested viruses. The SARS-1 genome harbored 11 genes encoding 12 proteins, while SARS-2 genome contained only 10 genes encoding for 10 proteins. MERS genome contained 11 genes encoding 11 proteins. The analysis also revealed a slight variation in the whole genome size of SARS-2 comparing to its siblings resulting from sequential insertions and deletions (indels) throughout the viral genome particularly ORF1AB, spike, ORF10 and ORF8. The effective indels were observed in the gene encoding the spike protein that is responsible for viral attachment to the angiotensin-converting enzyme 2 (ACE2) cell receptor and initiating infection. These indels are responsible for the newly emerging COVID-19 variants αCoV, βCoV, γCoV and δCoV. Nowadays, few effective COVID-19 vaccines developed based on spike (S) glycoprotein were approved and become available worldwide. Currently available vaccines can relatively prevent the spread of COVID-19 and suppress the disease. The traditional (killed or attenuated virus vaccine and antibody-based vaccine) and innovated vaccine production technologies (RNA- and DNA-based vaccines and viral vectors) are summarized in this review. We finally highlight the most common questions related to COVID-19 disease and the benefits of getting vaccinated.
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60% (6,309/10,598) of mothers had a scar. The maternal-scar/no-scar admission aIRR was 0.96 (0.81–1.14) from 0 to 6 weeks and 1.12 (0.97–1.28) for 6 weeks-3 years. The 6-week in-hospital case-fatality infection aRR was 0.59 (0.34–1.05); 0.40 (0.17–0.91) for males and 0.86 (0.38–1.94) for females. Protection was especially evident against sepsis, the overall 6-week aRR=0.49 (0.26–0.91); no effect was observed for non-infectious deaths or after 6 weeks of age. Effects were similar across BCG strains and multivariate models adjusted for socioeconomic status did not affect estimates.
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¹: Joint first authors.

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Non-specific effect of Bacille Calmette-Guérin vaccine on the immune response to routine immunisations

Highlights

Abstract

Section snippets

Background

Study design and population

Results

Discussion

Acknowledgements

Lancet

J Urol

Eur J Cancer

Lancet

Cell Host Microbe

Vaccine

Lancet

Vaccine

Vaccine

Vaccine

Vaccine

Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature

JAMA

Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis

Int J Epidemiol

Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease

Infect Immun

The non-specific effects of vaccines

Arch Dis Child

Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors

J Urol

Does BCG vaccination protect against the development of childhood asthma? A systematic review and meta-analysis of epidemiological studies

Int J Epidemiol

Effect of Bacillus Calmette-Guerin vaccination on new-onset type 1 diabetes. A randomized clinical study

Diabetes Care

Neonatal Bacille Calmette-Guerin vaccination and type 1 diabetes

Diabetes Care

Bacillus Calmette-Guerin vaccination and infant mortality

Expert Rev Vaccines

Randomized trials to study the nonspecific effects of vaccines in children in low-income countries

Pediatr Infect Dis J

Non-specific effects of vaccines in developing countries. We need evidence about the effect of vaccines on mortality from all causes

BMJ

Low birth weight infants and Calmette-Guerin bacillus vaccination at birth: community study from Guinea-Bissau

Pediatr Infect Dis J

Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa

BMJ

Non-specific effects of vaccination on child survival? A prospective study in Senegal

Trop Med Int Health

Evaluation of non-specific effects of infant immunizations on early infant mortality in a southern Indian population

Trop Med Int Health