title: Cross-reactive antibodies enhance live attenuated virus infection for increased immunogenicity.
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.
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
authors.forename: Kuan Rong
authors.initials: KR
authors.lastname: Chan
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
authors.forename: Wilfried A A
authors.identifier: http://orcid.org/0000-0002-7974-5288
authors.initials: WAA
authors.lastname: Saron
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
authors.forename: Esther Shuyi
authors.initials: ES
authors.lastname: Gan
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
authors.forename: Hwee Cheng
authors.initials: HC
authors.lastname: Tan
authors.affiliation: Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.
authors.forename: Darren Z L
authors.initials: DZL
authors.lastname: Mok
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
authors.forename: Summer Li-Xin
authors.initials: SL
authors.lastname: Zhang
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology (SMART), Singapore 138602.|KK Research Centre, KK Women's and Children's Hospital, Singapore 229899.
authors.forename: Yie Hou
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology (SMART), Singapore 138602.
authors.forename: Cui
authors.initials: C
authors.lastname: Liang
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, Singapore 169856.
authors.forename: Limin
authors.initials: L
authors.lastname: Wijaya
authors.affiliation: Centre for Computational Biology, Duke-NUS Medical School, Singapore 169857.
authors.forename: Sujoy
authors.identifier: http://orcid.org/0000-0002-7601-165X
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Center for Quantitative Medicine, Duke-NUS Medical School, Singapore 169857.|Department for International Health, University of Tampere, 33100 Finland.
authors.forename: Yin Bun
authors.initials: YB
authors.lastname: Cheung
authors.affiliation: Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology (SMART), Singapore 138602.|Department of Biological Engineering and Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Tannenbaum
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.|Department of Immunology and the Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.
authors.forename: Ashley L
authors.initials: AL
authors.lastname: St John
authors.affiliation: Department of Infectious Diseases, Singapore General Hospital, Singapore 169856.
authors.forename: Jenny G H
authors.initials: JGH
authors.lastname: Low
authors.affiliation: Program in Emerging Infectious Diseases, Duke-NUS Medical School, Singapore 169857.|Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.|Interdisciplinary Research Group in Infectious Diseases, Singapore-MIT Alliance for Research & Technology (SMART), Singapore 138602.
authors.forename: Eng Eong
authors.initials: EE
authors.lastname: Ooi