Dataset Information

Neonatal BCG Vaccination Reduces Interferon-? Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial.

ABSTRACT: BACKGROUND:BCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization. METHODS:A whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulants (killed pathogens) and Toll-like receptor (TLR) ligands. RESULTS:Compared to BCG-naive infants, BCG-vaccinated infants had increased production of interferon gamma (IFN-?) and monokine induced by gamma interferon (MIG) (CXCL9) in response to mycobacterial stimulation and decreased production of IFN-? in response to heterologous stimulation and TLR ligands. Reduced IFN-? responses were attributable to a decrease in the proportion of infants who mounted a detectable IFN-? response. BCG-vaccinated infants also had increased production of MIG (CXCL9) and interleukin-8 (IL-8), and decreased production of IL-10, macrophage inflammatory protein-1? (MIP-1?), and MIP-1?, the pattern of which varied by stimulant. IL-1Ra responses following TLR1/2 (Pam3CYSK4) stimulation were increased in BCG-vaccinated infants. Both sex and maternal BCG vaccination status influenced the effect of neonatal BCG vaccination. CONCLUSIONS:BCG vaccination leads to changes in IFN-? responsiveness to heterologous stimulation. BCG-induced changes in other cytokine responses to heterologous stimulation vary by pathogen.

SUBMITTER: Freyne B

PROVIDER: S-EPMC7289544 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial.

Freyne Bridget B Messina Nicole L NL Donath Susan S Germano Susie S Bonnici Rhian R Gardiner Kaya K Casalaz Dan D Robins-Browne Roy M RM Netea Mihai G MG Flanagan Katie L KL Kollmann Toby T Curtis Nigel N

The Journal of infectious diseases 20200601 12

<h4>Background</h4>BCG vaccination has beneficial nonspecific (heterologous) effects that protect against nonmycobacterial infections. We have previously reported that BCG vaccination at birth alters in vitro cytokine responses to heterologous stimulants in the neonatal period. This study investigated heterologous responses in 167 infants in the same trial 7 months after randomization.<h4>Methods</h4>A whole-blood assay was used to interrogate in vitro cytokine responses to heterologous stimulan ...[more]

PMID: 31990350

Similar Datasets

Project description:BACKGROUND:Mycobacterium bovis BCG vaccine has displayed inconsistent efficacy in different trials conducted in various geographical regions. Nevertheless, it significantly reduces the risk of severe childhood tuberculosis and continues to be used to prevent tuberculosis in many countries. Many studies revealed that efficacy of vaccine wanes with age. Most of the studies were based on in vivo and in vitro responses to tuberculin. With the advent of newer tests such as in vitro interferon-gamma assays and identification of potent immunogenic mycobacterial proteins there is a need to corroborate the observations. This study aims at ascertaining the need for a booster at a later age as indicated by in vitro release of IFN-gamma while evaluating Ag85A as an antigen. METHODS:Ninety healthy children who were without any clinical evidence of the disease, 45 with a BCG-scar and the remaining 45 without scar and 25 with tuberculosis were included in the study. The incidence of TB was analyzed in 216 children attending a DOTS clinic during 1996-2005. CD3+, CD4+ and CD8+ cell counts were measured by Flow cytometry. r32kDaBCG (Ag85A-BCG) protein was used to stimulate T cells in in vitro T cell responses and interferon-gamma (IFN-gamma) cytokine levels in the supernatants were measured by ELISA. RESULTS:High incidence of TB was observed in age group 13-14 years followed by children in the age group 10-12 years (Chi-square 242.22; p < 0.000). T cell subsets were within the normal range in all subjects. 79% of vaccinated children showed positive proliferative responses with a mean SI value of 4.98 +/- 1.99 while only 39% of the unvaccinated and 58% of the tuberculosis children showed positive responses with mean values of 2.9 +/- 1.6 (p < 0.001) and 2.9 +/- 1.7(p < 0.057), respectively. The stimulation indices in vaccinated children decreased in the older children concurring with an increase in the incidence of TB. CONCLUSION:Significantly high levels of in vitro IFN-gamma demonstrated in BCG vaccinated children in our study substantiate the observation that BCG is effective in children, but the effect may wane with age. The immunity could be boosted using modified r32kDa (Ag85A) of BCG.

Dataset Information

Neonatal BCG Vaccination Reduces Interferon-? Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial.

Publications

Neonatal BCG Vaccination Reduces Interferon-γ Responsiveness to Heterologous Pathogens in Infants From a Randomized Controlled Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets