Protein/AS01B vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors

Cell Rep Med. 2021 Feb 22;2(3):100207. doi: 10.1016/j.xcrm.2021.100207. eCollection 2021 Mar 16.

Abstract

Interactions between B cells and CD4+ T follicular helper (Tfh) cells are key determinants of humoral responses. Using samples from clinical trials performed with the malaria vaccine candidate antigen Plasmodium falciparum merozoite protein (PfRH5), we compare the frequency, phenotype, and gene expression profiles of PfRH5-specific circulating Tfh (cTfh) cells elicited by two leading human vaccine delivery platforms: heterologous viral vector prime boost and protein with AS01B adjuvant. We demonstrate that the protein/AS01B platform induces a higher-magnitude antigen-specific cTfh cell response and that this correlates with peak anti-PfRH5 IgG concentrations, frequency of PfRH5-specific memory B cells, and antibody functionality. Furthermore, our data indicate a greater Th2/Tfh2 skew within the polyfunctional response elicited following vaccination with protein/AS01B as compared to a Th1/Tfh1 skew with viral vectors. These data highlight the impact of vaccine platform on the cTfh cell response driving humoral immunity, associating a high-magnitude, Th2-biased cTfh response with potent antibody production.

Trial registration: ClinicalTrials.gov NCT02927145.

Keywords: AS01; T follicular helper cells; Tfh cells; Th1; Th2; adaptive immunity; antibody; clinical trials; heterologous viral vectors; malaria; vaccines.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / immunology
  • Adolescent
  • Adult
  • Antibodies, Protozoan / biosynthesis*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • Carrier Proteins / administration & dosage
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Vectors / chemistry
  • Genetic Vectors / immunology
  • Humans
  • Immunity, Humoral / drug effects*
  • Immunogenicity, Vaccine
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-5 / genetics
  • Interleukin-5 / immunology
  • Lipid A / administration & dosage
  • Lipid A / analogs & derivatives
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / genetics
  • Malaria Vaccines / immunology*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology
  • Malaria, Falciparum / prevention & control*
  • Male
  • Middle Aged
  • Plasmodium falciparum / immunology*
  • Receptors, CXCR5 / genetics
  • Receptors, CXCR5 / immunology
  • Saponins / administration & dosage
  • T Follicular Helper Cells / cytology
  • T Follicular Helper Cells / immunology
  • Th2 Cells / cytology
  • Th2 Cells / immunology
  • Vaccination
  • Vaccines, Subunit
  • Vaccinia virus / genetics
  • Vaccinia virus / immunology

Substances

  • AS01B adjuvant
  • Antibodies, Protozoan
  • CXCR5 protein, human
  • Carrier Proteins
  • IFNG protein, human
  • IL5 protein, human
  • Interleukin-5
  • Lipid A
  • Malaria Vaccines
  • RH5 protein, Plasmodium falciparum
  • Receptors, CXCR5
  • Saponins
  • Vaccines, Subunit
  • Interferon-gamma

Associated data

  • ClinicalTrials.gov/NCT02927145