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Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response.

Publication ,  Journal Article
McNamara, HA; Idris, AH; Sutton, HJ; Vistein, R; Flynn, BJ; Cai, Y; Wiehe, K; Lyke, KE; Chatterjee, D; Kc, N; Chakravarty, S; Lee Sim, BK ...
Published in: Cell Host Microbe
October 7, 2020

Generating sufficient antibody to block infection is a key challenge for vaccines against malaria. Here, we show that antibody titers to a key target, the repeat region of the Plasmodium falciparum circumsporozoite protein (PfCSP), plateaued after two immunizations in a clinical trial of the radiation-attenuated sporozoite vaccine. To understand the mechanisms limiting vaccine responsiveness, we developed immunoglobulin (Ig)-knockin mice with elevated numbers of PfCSP-binding B cells. We determined that recall responses were inhibited by antibody feedback, potentially via epitope masking of the immunodominant PfCSP repeat region. Importantly, the amount of antibody that prevents boosting is below the amount of antibody required for protection. Finally, while antibody feedback limited responses to the PfCSP repeat region in vaccinated volunteers, potentially protective subdominant responses to PfCSP C-terminal regions expanded with subsequent boosts. These data suggest that antibody feedback drives the diversification of immune responses and that vaccination for malaria will require targeting multiple antigens.

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Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

October 7, 2020

Volume

28

Issue

4

Start / End Page

572 / 585.e7

Location

United States

Related Subject Headings

  • Vaccines, Attenuated
  • Vaccination
  • Sporozoites
  • Plasmodium falciparum
  • Mutation
  • Mice, Inbred C57BL
  • Mice
  • Malaria Vaccines
  • Malaria
  • Immunology
 

Citation

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Chicago
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McNamara, H. A., Idris, A. H., Sutton, H. J., Vistein, R., Flynn, B. J., Cai, Y., … Cockburn, I. A. (2020). Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response. Cell Host Microbe, 28(4), 572-585.e7. https://doi.org/10.1016/j.chom.2020.07.001
McNamara, Hayley A., Azza H. Idris, Henry J. Sutton, Rachel Vistein, Barbara J. Flynn, Yeping Cai, Kevin Wiehe, et al. “Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response.Cell Host Microbe 28, no. 4 (October 7, 2020): 572-585.e7. https://doi.org/10.1016/j.chom.2020.07.001.
McNamara HA, Idris AH, Sutton HJ, Vistein R, Flynn BJ, Cai Y, et al. Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response. Cell Host Microbe. 2020 Oct 7;28(4):572-585.e7.
McNamara, Hayley A., et al. “Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response.Cell Host Microbe, vol. 28, no. 4, Oct. 2020, pp. 572-585.e7. Pubmed, doi:10.1016/j.chom.2020.07.001.
McNamara HA, Idris AH, Sutton HJ, Vistein R, Flynn BJ, Cai Y, Wiehe K, Lyke KE, Chatterjee D, Kc N, Chakravarty S, Lee Sim BK, Hoffman SL, Bonsignori M, Seder RA, Cockburn IA. Antibody Feedback Limits the Expansion of B Cell Responses to Malaria Vaccination but Drives Diversification of the Humoral Response. Cell Host Microbe. 2020 Oct 7;28(4):572-585.e7.
Journal cover image

Published In

Cell Host Microbe

DOI

EISSN

1934-6069

Publication Date

October 7, 2020

Volume

28

Issue

4

Start / End Page

572 / 585.e7

Location

United States

Related Subject Headings

  • Vaccines, Attenuated
  • Vaccination
  • Sporozoites
  • Plasmodium falciparum
  • Mutation
  • Mice, Inbred C57BL
  • Mice
  • Malaria Vaccines
  • Malaria
  • Immunology