A delayed fractionated dose RTS,S AS01 vaccine regimen mediates protection via improved T follicular helper and B cell responses

Elife. 2020 Apr 29;9:e51889. doi: 10.7554/eLife.51889.

Abstract

Malaria-071, a controlled human malaria infection trial, demonstrated that administration of three doses of RTS,S/AS01 malaria vaccine given at one-month intervals was inferior to a delayed fractional dose (DFD) schedule (62.5% vs 86.7% protection, respectively). To investigate the underlying immunologic mechanism, we analyzed the B and T peripheral follicular helper cell (pTfh) responses. Here, we show that protection in both study arms was associated with early induction of functional IL-21-secreting circumsporozoite (CSP)-specific pTfh cells, together with induction of CSP-specific memory B cell responses after the second dose that persisted after the third dose. Data integration of key immunologic measures identified a subset of non-protected individuals in the standard (STD) vaccine arm who lost prior protective B cell responses after receiving the third vaccine dose. We conclude that the DFD regimen favors persistence of functional B cells after the third dose.

Keywords: human; immunology; inflammation; malaria vaccine immunity; tfh and malaria vaccine; tfh, b cells and vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Protozoan / immunology*
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • Humans
  • Interleukins / immunology
  • Interleukins / metabolism
  • Malaria / immunology
  • Malaria / prevention & control*
  • Malaria Vaccines / administration & dosage*
  • Malaria Vaccines / immunology
  • Malaria Vaccines / pharmacology*
  • Malaria, Falciparum / immunology
  • Plasmodium falciparum / immunology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • Time Factors

Substances

  • Antibodies, Protozoan
  • Interleukins
  • Malaria Vaccines
  • interleukin-21

Grant support

The funder contributed to conceptualization, data review and manuscript preparation