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Chan KR, Wang X, Saron WAA, et al. Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity. Nat Microbiol. 2016;1:16164doi: 10.1038/nmicrobiol.2016.164.
Chan, K. R., Wang, X., Saron, W. A. A., Gan, E. S., Tan, H. C., Mok, D. Z. L., Zhang, S. L., Lee, Y. H., Liang, C., Wijaya, L., Ghosh, S., Cheung, Y. B., Tannenbaum, S. R., Abraham, S. N., St John, A. L., Low, J. G. H., & Ooi, E. E. (2016). Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity. Nature microbiology, 116164. https://doi.org/10.1038/nmicrobiol.2016.164
Chan, Kuan Rong, et al. "Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity." Nature microbiology vol. 1 (2016): 16164. doi: https://doi.org/10.1038/nmicrobiol.2016.164
Chan KR, Wang X, Saron WAA, Gan ES, Tan HC, Mok DZL, Zhang SL, Lee YH, Liang C, Wijaya L, Ghosh S, Cheung YB, Tannenbaum SR, Abraham SN, St John AL, Low JGH, Ooi EE. Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity. Nat Microbiol. 2016 Sep 19;1:16164. doi: 10.1038/nmicrobiol.2016.164. PMID: 27642668; PMCID: PMC7097525.
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Nat Microbiol. 2016 Sep 19;1:16164. doi: 10.1038/nmicrobiol.2016.164.

Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity.

Nature microbiology

Kuan Rong Chan, Xiaohui Wang, Wilfried A A Saron, Esther Shuyi Gan, Hwee Cheng Tan, Darren Z L Mok, Summer Li-Xin Zhang, Yie Hou Lee, Cui Liang, Limin Wijaya, Sujoy Ghosh, Yin Bun Cheung, Steven R Tannenbaum, Soman N Abraham, Ashley L St John, Jenny G H Low, Eng Eong Ooi

Affiliations

  1. Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
  2. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
  3. Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology (SMART), Singapore 138602.
  4. KK Research Centre, KK Women's and Children's Hospital, Singapore 229899.
  5. Department of Infectious Diseases, Singapore General Hospital, Singapore 169856.
  6. Centre for Computational Biology, Duke-NUS Medical School, Singapore 169857.
  7. Center for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857.
  8. Department for International Health, University of Tampere, 33100 Finland.
  9. Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
  10. Department of Immunology and the Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.

PMID: 27642668 PMCID: PMC7097525 DOI: 10.1038/nmicrobiol.2016.164

Abstract

Vaccination has achieved remarkable successes in the control of childhood viral diseases. To control emerging infections, however, vaccines will need to be delivered to older individuals who, unlike infants, probably have had prior infection or vaccination with related viruses and thus have cross-reactive antibodies against the vaccines. Whether and how these cross-reactive antibodies impact live attenuated vaccination efficacy is unclear. Using an open-label randomized trial design, we show that subjects with a specific range of cross-reactive antibody titres from a prior inactivated Japanese encephalitis vaccination enhanced yellow fever (YF) immunogenicity upon YF vaccination. Enhancing titres of cross-reactive antibodies prolonged YF vaccine viraemia, provoked greater pro-inflammatory responses, and induced adhesion molecules intrinsic to the activating Fc-receptor signalling pathway, namely immune semaphorins, facilitating immune cell interactions and trafficking. Our findings clinically demonstrate antibody-enhanced infection and suggest that vaccine efficacy could be improved by exploiting cross-reactive antibodies.

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