The influence of neonatal BCG vaccination on in vitro cytokine responses to Plasmodium falciparum.
BCG
Cytokine
Immunity
Malaria
Neonate
Non-specific effects
Plasmodium falciparum
Journal
BMC immunology
ISSN: 1471-2172
Titre abrégé: BMC Immunol
Pays: England
ID NLM: 100966980
Informations de publication
Date de publication:
30 Apr 2024
30 Apr 2024
Historique:
received:
17
10
2023
accepted:
11
03
2024
medline:
1
5
2024
pubmed:
1
5
2024
entrez:
30
4
2024
Statut:
epublish
Résumé
Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli. No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli. These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.
Sections du résumé
BACKGROUND
BACKGROUND
Bacillus Calmette-Guérin (BCG) vaccination has off-target protective effects against infections unrelated to tuberculosis. Among these, murine and human studies suggest that BCG vaccination may protect against malaria. We investigated whether BCG vaccination influences neonatal in vitro cytokine responses to Plasmodium falciparum. Blood samples were collected from 108 participants in the Melbourne Infant Study BCG for Allergy and Infection Reduction (MIS BAIR) randomised controlled trial (Clinical trials registration NCT01906853, registered July 2013), seven days after randomisation to neonatal BCG (n = 66) or no BCG vaccination (BCG-naïve, n = 42). In vitro cytokine responses were measured following stimulation with P. falciparum-infected erythrocytes (PfIE) or E. coli.
RESULTS
RESULTS
No difference in the measured cytokines were observed between BCG-vaccinated and BCG-naïve neonates following stimulation with PfIE or E. coli. However, age at which blood was sampled was independently associated with altered cytokine responses to PfIE. Being male was also independently associated with increased TNF-a responses to both PfIE and E. coli.
CONCLUSION
CONCLUSIONS
These findings do not support a role for BCG vaccination in influencing in vitro neonatal cytokine responses to P. falciparum. Older neonates are more likely to develop P. falciparum-induced IFN-γ and IFN-γ-inducible chemokine responses implicated in early protection against malaria and malaria pathogenesis.
Identifiants
pubmed: 38689233
doi: 10.1186/s12865-024-00611-5
pii: 10.1186/s12865-024-00611-5
doi:
Substances chimiques
BCG Vaccine
0
Cytokines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
24Subventions
Organisme : Australian National Health and Medical Research Council
ID : GNT1092789
Organisme : Australian National Health and Medical Research Council
ID : GNT1051228
Informations de copyright
© 2024. The Author(s).
Références
World Health Organisation. World malaria report 2022. Geneva: World Health Organisation; 2022.
Zimmermann P, Finn A, Curtis N, Does BCG. Vaccination protect against nontuberculous mycobacterial infection? A systematic review and Meta-analysis. J Infect Dis. 2018;218(5):679–87.
doi: 10.1093/infdis/jiy207
pubmed: 29635431
Higgins JP, Soares-Weiser K, López-López JA, Kakourou A, Chaplin K, Christensen H, et al. Association of BCG, DTP, and measles containing vaccines with childhood mortality: systematic review. BMJ. 2016;355:i5170.
doi: 10.1136/bmj.i5170
pubmed: 27737834
pmcid: 5063034
Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, et al. Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period? J Infect Dis. 2011;204(2):245–52.
doi: 10.1093/infdis/jir240
pubmed: 21673035
Pollard AJ, Finn A, Curtis N. Non-specific effects of vaccines: plausible and potentially important, but implications uncertain. Arch Dis Child. 2017;102(11):1077–81.
doi: 10.1136/archdischild-2015-310282
pubmed: 28501809
Netea MG, Joosten LAB, Latz E, Mills KHG, Natoli G, Stunnenberg HG, et al. Trained immunity: a program of innate immune memory in health and disease. Science. 2016;352(6284):aaf1098.
doi: 10.1126/science.aaf1098
pubmed: 27102489
pmcid: 5087274
Roth A, Gustafson P, Nhaga A, Djana Q, Poulsen A, Garly ML, et al. BCG vaccination scar associated with better childhood survival in Guinea-Bissau. Int J Epidemiol. 2005;34(3):540–7.
doi: 10.1093/ije/dyh392
pubmed: 15659474
Berendsen ML, van Gijzel SW, Smits J, de Mast Q, Aaby P, Benn CS, et al. BCG vaccination is associated with reduced malaria prevalence in children under the age of 5 years in sub-saharan Africa. BMJ Glob Health. 2019;4(6):e001862.
doi: 10.1136/bmjgh-2019-001862
pubmed: 31798997
pmcid: 6861070
Jensen KJ, Biering-Sorensen S, Ursing J, Kofoed PL, Aaby P, Benn CS. Seasonal variation in the non-specific effects of BCG vaccination on neonatal mortality: three randomised controlled trials in Guinea-Bissau. BMJ Glob Health. 2020;5(3):e001873.
doi: 10.1136/bmjgh-2019-001873
pubmed: 32201619
pmcid: 7059430
Walk J, de Bree LCJ, Graumans W, Stoter R, van Gemert GJ, van de Vegte-Bolmer M, et al. Outcomes of controlled human malaria infection after BCG vaccination. Nat Commun. 2019;10(1):874.
doi: 10.1038/s41467-019-08659-3
pubmed: 30787276
pmcid: 6382772
Clark IA, Allison AC, Cox FE. Protection of mice against Babesia and Plasmodium with BCG. Nature. 1976;259(5541):309–11.
doi: 10.1038/259309a0
pubmed: 765838
Cao DH, Wang JC, Liu J, Du YT, Cui LW, Cao YM. Bacillus Calmette-Guerin-inoculation at different time points influences the outcome of C57BL/6 mice infected with Plasmodium Chabaudi Chabaudi AS. Folia Parasitol (Praha). 2016;63.
Parra M, Liu X, Derrick SC, Yang A, Tian J, Kolibab K, et al. Molecular analysis of non-specific protection against murine malaria induced by BCG vaccination. PLoS ONE. 2013;8(7):e66115.
doi: 10.1371/journal.pone.0066115
pubmed: 23861742
pmcid: 3701530
Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012;109(43):17537–42.
doi: 10.1073/pnas.1202870109
pubmed: 22988082
pmcid: 3491454
Kleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Jacobs C, Xavier RJ, et al. BCG-induced trained immunity in NK cells: role for non-specific protection to infection. Clin Immunol. 2014;155(2):213–9.
doi: 10.1016/j.clim.2014.10.005
pubmed: 25451159
pmcid: 5084088
Messina NL, Gardiner K, Donath S, Flanagan K, Ponsonby AL, Shann F, et al. Study protocol for the Melbourne Infant Study: BCG for Allergy and infection reduction (MIS BAIR), a randomised controlled trial to determine the non-specific effects of neonatal BCG vaccination in a low-mortality setting. BMJ Open. 2019;9(12):e032844.
doi: 10.1136/bmjopen-2019-032844
pubmed: 31843845
pmcid: 6924750
Freyne B, Donath S, Germano S, Gardiner K, Casalaz D, Robins-Browne RM, et al. Neonatal BCG vaccination influences cytokine responses to toll-like receptor ligands and Heterologous Antigens. J Infect Dis. 2018;217(11):1798–808.
doi: 10.1093/infdis/jiy069
pubmed: 29415180
Pittet LF, Cox L, Freyne B, Germano S, Bonnici R, Gardiner K, et al. Hepatitis B vaccine co-administration influences the heterologous effects of neonatal BCG vaccination in a sex-differential manner. Vaccine. 2022;40(9):1334–41.
doi: 10.1016/j.vaccine.2022.01.005
pubmed: 35105495
Chandrasiri UP, Randall LM, Saad AA, Bashir AM, Rogerson SJ, Adam I. Low antibody levels to pregnancy-specific malaria antigens and heightened cytokine responses associated with severe malaria in pregnancy. J Infect Dis. 2014;209(9):1408–17.
doi: 10.1093/infdis/jit646
pubmed: 24277742
Freyne B, Messina NL, Donath S, Germano S, Bonnici R, Gardiner K, et al. Neonatal BCG vaccination reduces Interferon-gamma responsiveness to Heterologous Pathogens in infants from a Randomized Controlled Trial. J Infect Dis. 2020;221(12):1999–2009.
doi: 10.1093/infdis/jiaa030
pubmed: 31990350
pmcid: 7289544
Lee AH, Shannon CP, Amenyogbe N, Bennike TB, Diray-Arce J, Idoko OT, et al. Dynamic molecular changes during the first week of human life follow a robust developmental trajectory. Nat Commun. 2019;10(1):1092.
doi: 10.1038/s41467-019-08794-x
pubmed: 30862783
pmcid: 6414553
Popa GL, Popa MI. Recent advances in understanding the inflammatory response in Malaria: a review of the dual role of cytokines. J Immunol Res. 2021;2021:7785180.
doi: 10.1155/2021/7785180
pubmed: 34790829
pmcid: 8592744
Smith SG, Kleinnijenhuis J, Netea MG, Dockrell HM. Whole blood profiling of Bacillus Calmette-Guérin-Induced trained Innate Immunity in infants identifies epidermal growth factor, IL-6, platelet-derived growth Factor-AB/BB, and natural killer cell activation. Front Immunol. 2017;8:644.
doi: 10.3389/fimmu.2017.00644
pubmed: 28634479
pmcid: 5459878
Kandasamy R, Voysey M, McQuaid F, de Nie K, Ryan R, Orr O, et al. Non-specific immunological effects of selected routine childhood immunisations: systematic review. BMJ. 2016;355:i5225.
doi: 10.1136/bmj.i5225
pubmed: 27737830
pmcid: 5063033
Nissen TN, Birk NM, Blok BA, Arts RJW, Andersen A, Kjaergaard J, et al. Bacillus Calmette-Guerin vaccination at birth and in vitro cytokine responses to non-specific stimulation. A randomized clinical trial. Eur J Clin Microbiol Infect Dis. 2018;37(1):29–41.
doi: 10.1007/s10096-017-3097-2
pubmed: 28890996
Dodoo D, Omer FM, Todd J, Akanmori BD, Koram KA, Riley EM. Absolute levels and ratios of proinflammatory and anti-inflammatory cytokine production in vitro predict clinical immunity to Plasmodium Falciparum malaria. J Infect Dis. 2002;185(7):971–9.
doi: 10.1086/339408
pubmed: 11920322
D’Ombrain MC, Robinson LJ, Stanisic DI, Taraika J, Bernard N, Michon P, et al. Association of early interferon-gamma production with immunity to clinical malaria: a longitudinal study among Papua New Guinean children. Clin Infect Dis. 2008;47(11):1380–7.
doi: 10.1086/592971
pubmed: 18947328
Luty AJ, Lell B, Schmidt-Ott R, Lehman LG, Luckner D, Greve B, et al. Interferon-gamma responses are associated with resistance to reinfection with Plasmodium Falciparum in young African children. J Infect Dis. 1999;179(4):980–8.
doi: 10.1086/314689
pubmed: 10068595
Dunst J, Kamena F, Matuschewski K. Cytokines and chemokines in Cerebral Malaria Pathogenesis. Front Cell Infect Microbiol. 2017;7:324.
doi: 10.3389/fcimb.2017.00324
pubmed: 28775960
pmcid: 5517394
Ioannidis LJ, Nie CQ, Hansen DS. The role of chemokines in severe malaria: more than meets the eye. Parasitology. 2014;141(5):602–13.
doi: 10.1017/S0031182013001984
pubmed: 24476686
Miller JL, Sack BK, Baldwin M, Vaughan AM, Kappe SH. Interferon-mediated innate immune responses against malaria parasite liver stages. Cell Rep. 2014;7(2):436–47.
doi: 10.1016/j.celrep.2014.03.018
pubmed: 24703850
Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626–38.
doi: 10.1038/nri.2016.90
pubmed: 27546235
Zimmermann P, Curtis N. Factors that influence the Immune response to vaccination. Clin Microbiol Rev. 2019;32(2).
Casimir GJ, Heldenbergh F, Hanssens L, Mulier S, Heinrichs C, Lefevre N, et al. Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children. J Inflamm (Lond). 2010;7:28.
doi: 10.1186/1476-9255-7-28
pubmed: 20525175
Jagannathan P, Kakuru A, Okiring J, Muhindo MK, Natureeba P, Nakalembe M, et al. Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: a randomized controlled trial. PLoS Med. 2018;15(7):e1002606.
doi: 10.1371/journal.pmed.1002606
pubmed: 30016328
pmcid: 6049882
Biering-Sørensen S, Jensen KJ, Monterio I, Ravn H, Aaby P, Benn CS. Rapid Protective Effects of Early BCG on neonatal mortality among low Birth Weight boys: observations from randomized trials. J Infect Dis. 2018;217(5):759–66.
doi: 10.1093/infdis/jix612
pubmed: 29216358
Moris P, Bellanger A, Ofori-Anyinam O, Jongert E, Yarzabal Rodriguez JP, Janssens M. Whole blood can be used as an alternative to isolated peripheral blood mononuclear cells to measure in vitro specific T-cell responses in human samples. J Immunol Methods. 2021;492:112940.
doi: 10.1016/j.jim.2020.112940
pubmed: 33493551
Halsey LG, Curran-Everett D, Vowler SL, Drummond GB. The fickle P value generates irreproducible results. Nat Methods. 2015;12(3):179–85.
doi: 10.1038/nmeth.3288
pubmed: 25719825
Bakker OB, Aguirre-Gamboa R, Sanna S, Oosting M, Smeekens SP, Jaeger M, et al. Integration of multi-omics data and deep phenotyping enables prediction of cytokine responses. Nat Immunol. 2018;19(7):776–86.
doi: 10.1038/s41590-018-0121-3
pubmed: 29784908
pmcid: 6022810