Potent plasmablast-derived antibodies elicited by the National Institutes of Health dengue vaccine

Diogo M. Magnani, Cassia G.T. Silveira, Michael J. Ricciardi, Lucas Gonzalez-Nieto, Núria Pedreño-Lopez, Varian K. Bailey, Martin J. Gutman, Helen S. Maxwell, Aline Domingues, Priscilla R. Costa, Lilian Ferrari, Raphaella Goulart, Mauricio Martins, José M. Martinez-Navio, Sebastian P. Fuchs, Jorge Kalil, Maria do Carmo Timenetsky, Jens Wrammert, Stephen S. Whitehead, Dennis R. BurtonRonald Charles Desrosiers, Esper G. Kallas, David Watkins

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10 Scopus citations

Abstract

Exposure to dengue virus (DENV) is thought to elicit lifelong immunity, mediated by DENV-neutralizing antibodies (nAbs). However, Abs generated by primary infections confer serotype-specific protection, and immunity against other serotypes develops only after subsequent infections. Accordingly, the induction of these nAb responses acquired after serial DENV infections has been a long-soughtafter goal for vaccination. Nonetheless, it is still unclear if tetravalent vaccines can elicit or recall nAbs. In this study, we have characterized the responses from a volunteer who had been previously exposed to DENV and was immunized with the live attenuated tetravalent vaccine Butantan-DV, developed by the NIH and Butantan Institute. Eleven days after vaccination, we observed an ~70-fold expansion of the plasmablast population. We generated 21 monoclonal Abs (MAbs) from singly sorted plasmablasts. These MAbs were the result of clonal expansions and had significant levels of somatic hypermutation (SHM). Nineteen MAbs (90.5%) neutralized at least one DENV serotype at concentrations of 1 μg/ml or less; 6 of the 21 MAbs neutralized three or more serotypes. Despite the tetravalent composition of the vaccine, we observed a neutralization bias in the induced repertoire: DENV3 was targeted by 18 of the 19 neutralizing MAbs (nMAbs). Furthermore, the P3D05 nMAb neutralized DENV3 with extraordinary potency (concentration to achieve half-maximal neutralization [Neut50] = 0.03 μg/ml). Thus, the Butantan-DV vaccine engendered a mature, antigen-selected B cell repertoire. Our results suggest that preexisting responses elicited by a previous DENV3 infection were recalled by immunization.

Original languageEnglish (US)
Article numbere00867-17
JournalJournal of Virology
Volume91
Issue number22
DOIs
StatePublished - Nov 1 2017

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Keywords

  • B cell
  • Butantan-DV
  • Dengue
  • Monoclonal antibodies
  • Plasmablast
  • TV003
  • Vaccines

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Magnani, D. M., Silveira, C. G. T., Ricciardi, M. J., Gonzalez-Nieto, L., Pedreño-Lopez, N., Bailey, V. K., Gutman, M. J., Maxwell, H. S., Domingues, A., Costa, P. R., Ferrari, L., Goulart, R., Martins, M., Martinez-Navio, J. M., Fuchs, S. P., Kalil, J., Timenetsky, M. D. C., Wrammert, J., Whitehead, S. S., ... Watkins, D. (2017). Potent plasmablast-derived antibodies elicited by the National Institutes of Health dengue vaccine. Journal of Virology, 91(22), [e00867-17]. https://doi.org/10.1128/JVI.00867-17