Influence ofMycobacterium bovisBacillus Calmette-Guérin on Antibody and Cytokine Responses to Human Neonatal Vaccination

Abstract

The immaturity of the immune system increases the susceptibility of young infants to infectious diseases and prevents the induction of protective immune responses by vaccines. We previously reported that Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination induces a potent Th1 response to mycobacterial Ags in newborns. In this study, we evaluated the influence of BCG on the response to unrelated vaccines given in early life. Newborns were randomly allocated to one of three study groups receiving BCG at birth, when infants received their first dose of hepatitis B and oral polio vaccines; at 2 mo of age, when infants received their first dose of diphtheria and tetanus vaccines; or at 4.5 mo of age, when immune responses to vaccines were measured. Administration of BCG at the time of priming markedly increased the cellular and Ab responses to the hepatitis B vaccine, but had only a limited influence on the cytokine response to tetanus toxoid and no effect on the Ab responses to tetanus and diphtheria toxoids. Although BCG induced a potent Th1-type response to mycobacterial Ags, it promoted the production of both Th1- and Th2-type cytokines in response to unrelated vaccines. The effect of BCG was apparent at the systemic level, as it increased the Ab response to oral polio vaccine. These results demonstrate that BCG influences the immune response to unrelated Ags in early life, likely through its influence on the maturation of dendritic cells.

Genetic regulation of immune responses to vaccines in early life

“…28 Concentration of total serum IgG was determined by ELISA on goat anti-human IgG-(Zymed Laboratories San Francisco, CA, USA) coated plates. The incubation of serum samples was followed by successive addition of peroxidase-coupled goat anti-human IgG (Cappell-ICN, Costa Mesa, CA, USA) and ABTS substrate.…”

“…28 Briefly, peripheral blood mononuclear cells were incubated with mycobacterial antigens, including purified protein derivative (PPD, RT49, 10 mg/ml; Statens Serum Institut), shortterm culture filtrate (STCF, 10 mg/ml; a gift from Dr Peter Andersen, Statens Serum Institut), killed Mycobacterium tuberculosis and Ag85 (both at 10 mg/ml, and given by Dr Kris Huygen, Institut Pasteur du Brabant, Belgium) and Hsp 65 (10 mg/ml, GBF, Braunschweig, Germany), and to other vaccine antigens including TT (2 mg/ml; Chiron Behring, Marburg, Germany), Bordetella pertussis antigens (pertactin (PER), 5 mg/ml, pertussis toxin (PT), 5 mg/ml and filamentous haemagglutinin (FHA), 5 mg/ml, kindly provided by Glaxo SmithKline Biologicals) and phytohaemagglutinin (PHA, 5 mg/ml; Sigma Chemicals, Poole, Dorset, UK) or medium alone. IFN-g and interleukin-13 (IL-13) concentrations were measured in supernatants collected on day 2 (PHA) or day 6 (antigens and medium) using commercially available reagents (Biosource Europe, Fleurus, Belgium).…”

MTBVAC from discovery to clinical trials in tuberculosis-endemic countries

“…Another small study in low-birth-weight children conducted in the USA and the UK deduced that administration of BCG vaccine at first contact might contribute to lower mortality [24,25]. Moreover, neonatal BCG vaccination in clinic has been shown to induce a strong T H 1-cell-polarizing cytokine response that can enhance immune responses to other neonatal vaccines [26]. Recently, protection of neonatal BCG vaccination against hospitalization due to respiratory infection and sepsis in low TB endemic countries has been described [27].…”

High rate of Quantiferon positive and tuberculin negative tests in infants born at a large Italian University Hospital in 2011: a cautionary hypothesis

“…8,[9][10][11] Naive cells from the cord blood produce IFNgamma, IL-5, IL-13 (at low levels) if stimulated by PPD in vitro. 12 Similarly, low levels of IFN-gamma, IL-10 and IL-5 are produced by cells from the cord blood after stimulation with BCG in vitro. 13 In addition, IFN-gamma, IL-10, IL-12, and low levels of IL-13 and IL-5 but no IL-4 were produced by cord blood mononuclear cells after stimulation with BCG.…”