title: A randomized clinical trial in adults and newborns in South Africa to compare the safety and immunogenicity of bacille Calmette-Guérin (BCG) vaccine administration via a disposable-syringe jet injector to conventional technique with needle and syringe.
abstract: BACKGROUND
  Intradermal bacille Calmette-Guérin (BCG) vaccination by needle-free, disposable-syringe jet injectors (DSJI) is an alternative to the Mantoux method using needle and syringe (NS). We compared the safety and immunogenicity of BCG administration via the DSJI and NS techniques in adults and newborn infants at the South African Tuberculosis Vaccine Initiative (SATVI) research site in South Africa.
  
  
  METHODS
  Thirty adults and 66 newborn infants were randomized 1:1 to receive intradermal BCG vaccine (0.1 mL in adults; 0.05 mL in infants) via DSJI or NS. Wheal diameter (mm) and skin fluid deposition at the site of injection (SOI) were measured immediately post-vaccination. Adverse events and SOI reactogenicity data were collected 30 min and 1, 2, 4, and 12 weeks after vaccination for adults and at 30 min and 4, 10, and 14 weeks for infants. Blood was collected in infants at 10 and 14 weeks to assess BCG-specific T-cell immune responses.
  
  
  RESULTS
  More infant BCG vaccinations by DSJI deposited >5 μL fluid on the skin surface, compared to NS (49% versus 9%, p=0.001). However, all 12 infant vaccinations that did not produce any SOI wheal occurred in the NS group (36%, p<0.001). Median wheal diameter, in participants for which an SOI wheal formed, did not differ significantly between groups in infants (combined 3.0mm IQR 2.0 to 4.0, p=0.59) or in adults (combined 9.0mm IQR 7.0 to 10.0, p=0.13). Adverse events were similar between study arms. Proportion of participants with BCG scars after three months did not differ in adults (combined 97%, p=0.67) or infants (combined 62%, p=0.13). Frequencies of BCG-specific clusters of differentiation 4 (CD4) and clusters of differentiation 8 (CD8) T-cells co-expressing IFN-γ, TNF-α, IL-2, and/or IL-17 were not different in the DSJI and NS groups.
  
  
  CONCLUSIONS
  BCG vaccination of newborn infants via DSJI was more likely to deliver an appropriate intradermal wheal at the SOI as compared to NS, despite leaving more fluid on the surface of the skin. Safety, reactogenicity, and antigen-specific T-cell immune responses did not differ between DSJI and NS techniques.
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa. Electronic address: hennie.geldenhuys@uct.ac.za.
authors: Hennie D
authors: HD
authors: Geldenhuys
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa.
authors: Helen
authors: H
authors: Mearns
authors: PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98109, USA.
authors: Jennifer
authors: J
authors: Foster
authors: PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98109, USA.
authors: Eugene
authors: E
authors: Saxon
authors: Vaccine for Africa Initiative (VACFA), Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa.
authors: Benjamin
authors: B
authors: Kagina
authors: PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98109, USA.
authors: Laura
authors: L
authors: Saganic
authors: PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98109, USA.
authors: Courtney
authors: C
authors: Jarrahian
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa.
authors: Michele D
authors: MD
authors: Tameris
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa.
authors: One B
authors: OB
authors: Dintwe
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa.
authors: Michele
authors: M
authors: Van Rooyen
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa.
authors: Kany-Kany A
authors: KK
authors: Luabeya
authors: Vaccine for Africa Initiative (VACFA), Institute of Infectious Disease and Molecular Medicine (IDM), University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa.
authors: Gregory
authors: G
authors: Hussey
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa.
authors: Thomas J
authors: TJ
authors: Scriba
authors: South African Tuberculosis Vaccine Initiative (SATVI), Institute of Infectious Disease and Molecular Medicine (IDM) and Department of Paediatrics and Child Health, University of Cape Town, Brewelskloof Hospital, Haarlem Street, Worcester 6850, South Africa.
authors: Mark
authors: M
authors: Hatherill
authors: PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98109, USA.
authors: Darin
authors: D
authors: Zehrung
mesh_terms: D000293:Adolescent; D000328:Adult; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007271:Injections, Intradermal / Q000009:adverse effects / Q000379:methods; D007277:Injections, Jet / Q000009:adverse effects / Q000379:methods; D008297:Male; D008875:Middle Aged; D013019:South Africa; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult
chemical_list: D001500:BCG Vaccine; D016207:Cytokines
keywords: BCG; Intradermal vaccine; Jet injector; Mantoux; Vaccine administration