Journal article
Safety and immunogenicity of newborn MVA85A vaccination and selective, delayed Bacille Calmette-Guerin (BCG) for infants of HIV infected mothers: A phase 2 randomized controlled trial.
- Abstract:
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Background
Vaccination of HIV-infected infants with bacille Calmette-Guérin (BCG) is contraindicated. HIV-exposed newborns need a new tuberculosis (TB) vaccination strategy that protects against TB early in life; and avoids the potential risk of BCG disease until after HIV infection has been excluded.
Methods
This double-blind randomized controlled trial compared newborn MVA85A prime vaccination (1 x108 PFU) vs. Candin® control, followed by selective deferred BCG vaccination at 8 weeks of age for HIV-uninfected infants, and 12 months follow-up for safety and immunogenicity.
Results
248 HIV-exposed infants were enrolled. More frequent mild-moderate reactogenicity events were seen after newborn MVA85A vaccination, but no significant difference was observed in the rate of Severe or Serious Adverse Events; HIV acquisition (n=1 per arm); or incident TB disease (n=5 MVA85A; n=3 control) compared to the control arm. MVA85A vaccination induced modest, but significantly higher Ag85A-specific IFNγ+ CD4+ T cells compared to control at weeks 4 and 8 (p<0.0001). BCG did not further boost this response in MVA85A vaccinees. The BCG-induced Ag85A-specific IFNγ+ CD4+ T cell response at weeks 16 and 52 was of similar magnitude in the control arm compared to the MVA85A arm at all time points. Proliferative capacity, functional profiles and memory phenotype of BCG-specific CD4 responses were similar across study arms.
Conclusions
MVA85A prime vaccination of HIV-exposed newborns was safe and induced an early modest antigen-specific immune response that did not interfere with, or enhance, immunogenicity of subsequent BCG vaccination. New protein-subunit and viral-vectored TB vaccine candidates should be tested in HIV-exposed newborns.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Proof, pdf, 1.5MB, Terms of use)
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- Publisher copy:
- 10.1093/cid/cix834
Authors
- Publisher:
- Oxford University Press
- Journal:
- Clinical Infectious Diseases More from this journal
- Publication date:
- 2017-10-26
- Acceptance date:
- 2017-10-23
- DOI:
- EISSN:
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1537-6591
- ISSN:
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1058-4838
- Pmid:
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29028973
- Language:
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English
- Keywords:
- Pubs id:
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pubs:737323
- UUID:
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uuid:b0287863-f243-4de2-8eb2-79ef41e756bf
- Local pid:
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pubs:737323
- Source identifiers:
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737323
- Deposit date:
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2017-10-20
- ARK identifier:
Terms of use
- Copyright holder:
- McShane et al
- Copyright date:
- 2017
- Notes:
- © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
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