Population Differences in Immune Responses to Bacille Calmette‐Guérin Vaccination in Infancy

Lalor, Maeve K.; Ben-Smith, Anne; Gorak‐Stolinska, Patricia; Weir, Rosemary E.; Floyd, Sian; Blitz, Rose; Mvula, Hazzie; Newport, Melanie J.; Branson, Keith; McGrath, Nuala; Crampin, Amelia C.; Fine, Paul E. M.; Dockrell, Hazel M.

doi:10.1086/597069

Cited by 99 publications

(106 citation statements)

References 13 publications

(16 reference statements)

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“…To date, few data are available on the character of T-cell responses in older children, who are more likely to have been exposed to TB. Most studies in children have been performed after BCG vaccination in infants (44)(45)(46). These studies report lower frequencies of specific CD4 and also CD8 T cells in infants to those observed here in older children.…”

Section: Discussioncontrasting

confidence: 42%

CD4 and CD8 T-Cell Responses to Mycobacterial Antigens in African Children

Tena-Coki¹,

Scriba²,

Peteni³

et al. 2010

Am J Respir Crit Care Med

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Section: Discussioncontrasting

confidence: 42%

CD4 and CD8 T-Cell Responses to Mycobacterial Antigens in African Children

Tena-Coki¹,

Scriba²,

Peteni³

et al. 2010

Am J Respir Crit Care Med

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Section: Discussionsupporting

confidence: 80%

“…This is not the case for PPD stimulation, which induces relatively prominent IP-10, MCP-1, IL-8 and MDC responses in unvaccinated infants. As a PPD-specific Th-1 response appears to be absent in unvaccinated UK infants at this age (as indicated here by the lack of an IFN-γ response and also seen previously [24]), it appears that PPD possesses the capacity to stimulate certain chemokine or inflammatory-like responses even in a BCG-unprimed immune system.Of the cytokines previously measured in studies designed to demonstrate the multifunctionality of mycobacteria-specific T cells [7,22], IFN-γ, MIP-1β and TNF-α were prominent in the response to HBHA (respective increases of 112-, 105-and 55-fold in BCGvaccinated infants). Although increased fourfold in the vaccinated group, the presence of IL-2 in the biosignature of the HBHA response was much less marked, a finding that may relate to the kinetics of IL-2 release and degradation in the 7-day whole blood assay.…”

supporting

confidence: 80%

Broad heparin‐binding haemagglutinin‐specific cytokine and chemokine response in infants following Mycobacterium bovis BCG vaccination

et al. 2012

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Heparin-binding haemagglutinin (HBHA)-specific immune responses have been linked to protection against tuberculosis (TB).We investigated the hypothesis that BCG vaccination of human infants primes an HBHA-specific response, using multiplex to measure secreted cytokines and chemokines following HBHA and Mycobacterium tuberculosis purified protein derivative (PPD) stimulation of diluted whole blood samples from BCG-vaccinated or -unvaccinated infants. Of 42 analytes measured, 24 and 32 significant, BCG-associated increases were detected in response to HBHA and PPD, respectively. Both response profiles included Th-1, Th-2, Th-17 and inflammatory cytokines and chemokines (e.g. IFN-γ, TNF-α, IL-5, IL-10, IL-13, IL-17, MIP-1α and MIP-1β). We also found that six of the seven responses most closely correlated with IFN-γ were common to both HBHA and PPD. Notably, all HBHA-specific secretion of cytokines and chemokines from infant samples was dependant on previous BCG vaccination. Also, long-term persistence of HBHA-specific responses was found in adolescents with evidence of infant BCG vaccination. This study demonstrates for the first time BCG priming of an HBHA-specific immune response in infants that is characterised by a broad cytokine and chemokine signature. It also suggests a number of BCG vaccination associated, HBHA-induced responses that should be useful for future studies of biomarkers of protection against TB.Keywords: BCG vaccination r Chemokines r Cytokines r Heparin-binding haemagglutinin (HBHA) r tuberculosis Supporting Information available online IntroductionThe current global burden of tuberculosis (TB) disease is one of the greatest challenges to public health. That the problem is focussed in tropical countries is in part due to the lack of protective efficacy Correspondence: Dr. Steven G. Smith e-mail: steven.smith@lshtm.ac.uk of the BCG vaccine against adult pulmonary disease at lower latitudes [1]. Efforts towards the development of a more efficacious vaccine for TB should ensure that the resultant immune response is an improvement upon that induced by BCG in the regions where it is least effective.Infant BCG vaccination is a consistently efficacious and cost-effective preventative measure against childhood forms of TB [2,3]. There is also evidence that BCG not only affords 2512 Steven G. Smith et al. Eur. J. Immunol. 2012. 42: 2511-2522 protection to infants in more equatorial regions but that this protection is against all forms of TB and persists for 15-20 years [4]. The efficacy of infant BCG vaccination must therefore be considered when new TB vaccines designed to improve protection against adult pulmonary TB are developed and tested. Although homologous boosting of the BCG vaccine has proven ineffective [5], the immunity induced by prior BCG vaccination may be effectively boosted with selected antigens. Such a heterologous approach has seen the induction of strong, polyfunctional CD4 + T-cell responses in humans, specific for the mycobacterial antigen 85A, which was delivered via the modifi...

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“…The raised levels of post BCG immunization IFN-g at 6 months could be attributed only to the BCG vaccination administered at birth. Though several workers have measured IFN-g levels in infants and adults to test immunogenicity of BCG vaccine 21,[34][35][36][37] yet, as per available literature, there is no study to show changes in the IFN-g levels following BCG vaccination in moderately preterm newborn infants so far. Lalor et al and Black et al described population/ethnic/racial differences in the immune responses to IFN-g following BCG immunization to infants in UK from those immunized in Malawi.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity and safety of early vs delayed BCG vaccination in moderately preterm (31–33 weeks) infants

Saroha

Faridi

Batra

et al. 2015

Human Vaccines & Immunotherapeutics

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Minimum gestation at which infant can be given BCG (Bacillus Calmette-Guerin) vaccine safely at birth is not clearly defined. Our objectives were the following: to compare Mantoux test after 6 months of BCG immunization in moderately preterm babies (31-33 weeks) vaccinated at birth and 34 weeks post conception age and to compare in above groups:(a) Interferon -gamma (IFN-g) levels in BCG vaccinated infants who did not react to Mantoux test (b) Local BCG reaction at 6, 10, 14 weeks and 6 months (c) Complications of BCG vaccination. Interventional, randomized comparative trial. Moderately preterm infants (31-33 weeks), 90 in each group. At birth, 180 moderately preterm infants were recruited and randomly allocated into 2 groups. Two ml venous blood was drawn for estimation of IFN-g levels. Infants were given BCG vaccine within 72 hours of birth and followed up after 2, 4, 6, 10, 14 weeks and 6 months (group 1). Infants were recruited at birth and held up till 34 weeks post conception age (group 2) and then given BCG vaccine and followed up similarly as group 1. At each visit, local BCG reaction, any local or unusual complication and anthropometric measurements were noted. At six months, Mantoux test was done and 2 ml venous blood sample was collected for IFN-g levels post vaccination. Presence or absence of BCG local reaction, PPD conversion rates and complications were analyzed using Chi square or Fisher's exact test. IFN-g levels were analyzed by ANOVA. In all 117 infants could be followed till 6 months after BCG immunization in 2 groups, and Mantoux test was positive in 38.4% of them. The rate of Mantoux test positivity was similar irrespective of the age of giving BCG immunization (group 1-39.1% vs group 2-37.5%; p > 0.05). IFN-g levels were significantly raised at 6 months in 60% (n D 21/41) and 65% (n D 15/27) Mantoux negative infants in group 1 and group 2 respectively. The sequence and order of local BCG reaction at 2, 4, 6, 10, 14 weeks and 6 months was in the form of papule, pustule, ulcer, scab and scar. Scar was formed in 94.2% and 89.5% infants in group 1 and group 2 respectively. One infant in group 1 showed abortive reaction (0.85%). Only 3.4% of infants developed lymphadenopathy and was similar in both the groups. Moderately preterm infants (31-33 weeks) exhibited 98.3% immunogenicity after BCG immunization at birth and can be safely vaccinated without any risk of severe complications.

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Population Differences in Immune Responses to Bacille Calmette‐Guérin Vaccination in Infancy

Cited by 99 publications

References 13 publications

CD4 and CD8 T-Cell Responses to Mycobacterial Antigens in African Children

CD4 and CD8 T-Cell Responses to Mycobacterial Antigens in African Children

Broad heparin‐binding haemagglutinin‐specific cytokine and chemokine response in infants following Mycobacterium bovis BCG vaccination

Immunogenicity and safety of early vs delayed BCG vaccination in moderately preterm (31–33 weeks) infants

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