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The Effect of Bcg Revaccination on the Response to Unrelated Vaccines in Urban Ugandan Adolescents: Results of the Popvac C Randomised, Controlled Trial
26 Pages Posted: 21 Dec 2023
More...Abstract
Background: There is increasing evidence that immune responses induced by several important vaccines are reduced in low-income equatorial and rural settings, compared to high-income and urban settings. BCG immunisation has been shown to enhance responses to several unrelated vaccines in high-income populations. We hypothesized that revaccination with BCG might enhance responses to unrelated vaccines in Ugandan schoolchildren.
Methods: We designed an open-label, randomised, controlled trial of BCG revaccination versus no BCG revaccination to determine the effect on the immunogenicity of subsequent unrelated vaccines among schoolchildren aged 13–17 years from a Ugandan, urban birth cohort. Computer-generated 1:1 randomisation was implemented in REDCap. Participants received BCG or no BCG at week zero, followed by yellow fever, oral typhoid (Ty21a), and HPV-prime at week 4, and HPV-boost and tetanus/diphtheria at week 28. Primary outcomes (all participants, intention to treat) were vaccine responses at week 8 and, for tetanus/diphtheria, at week 52. Linear regression compared log-transformed outcomes between trial arms, with results back-transformed to geometric mean ratios (GMR). Registration ISRCTN10482904.
Results: Between 31st August and 12th October 2020, we enrolled 300 participants, 58% male, 151 in the BCG revaccination arm, and 149 in the no BCG arm, of whom 142 (94%) and 136 (91%), respectively, completed trial follow-up. There was no effect of BCG revaccination, compared to no BCG revaccination, on the response observed for any vaccine:yellow fever neutralising antibody (GMR 0.94 (95% confidence interval (CI) 0.75-1.19)); Salmonella Typhi O:LPS specific IgG (0.99 (0.80-1.23)), HPV-16 IgG (0.97 (0.69-1.35)), HPV-18 IgG (1.03 (0.76-1.40)), tetanus IgG (1.13 (0.87-1.47)) or diphtheria IgG (1.00 (0.87-1.16)). There were no serious adverse events.
Interpretation: We found no evidence that BCG revaccination is an effective strategy to improve immune responses to other vaccines in this setting.
Trial Registration: Registration ISRCTN10482904
Funding: UK Medical Research Council (MR/R02118X/1)
Declaration of Interest: All authors declare no competing interests.
Ethical Approval: The trial was approved by the ethics committees of the Uganda Virus Research Institute (reference: GC/127/18/09/682), the London School of Hygiene and Tropical Medicine (reference: 16034), the Uganda National Council for Science and Technology (reference: HS 2491) and the Uganda National Drug Authority (reference: CTA0094). We obtained written informed assent and consent from all participants and their guardians/ parents, respectively.
Keywords: BCG revaccination, vaccine response, Yellow fever, typhoid, HPV, tetanus, diphtheria, randomised controlled trial
Suggested Citation: Suggested Citation