Poly I:C elicits broader and stronger humoral and cellular responses to a Plasmodium vivax circumsporozoite protein malaria vaccine than Alhydrogel in mice

Front Immunol. 2024 Apr 8:15:1331474. doi: 10.3389/fimmu.2024.1331474. eCollection 2024.

Abstract

Malaria remains a global health challenge, necessitating the development of effective vaccines. The RTS,S vaccination prevents Plasmodium falciparum (Pf) malaria but is ineffective against Plasmodium vivax (Pv) disease. Herein, we evaluated the murine immunogenicity of a recombinant PvCSP incorporating prevalent polymorphisms, adjuvanted with Alhydrogel or Poly I:C. Both formulations induced prolonged IgG responses, with IgG1 dominance by the Alhydrogel group and high titers of all IgG isotypes by the Poly I:C counterpart. Poly I:C-adjuvanted vaccination increased splenic plasma cells, terminally-differentiated memory cells (MBCs), and precursors relative to the Alhydrogel-combined immunization. Splenic B-cells from Poly I:C-vaccinated mice revealed an antibody-secreting cell- and MBC-differentiating gene expression profile. Biological processes such as antibody folding and secretion were highlighted by the Poly I:C-adjuvanted vaccination. These findings underscore the potential of Poly I:C to strengthen immune responses against Pv malaria.

Keywords: TLR3-ligand; adjuvant; antibody-secreting cells; malaria; memory B cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic
  • Aluminum Hydroxide* / immunology
  • Animals
  • Antibodies, Protozoan* / immunology
  • Female
  • Immunity, Cellular
  • Immunity, Humoral
  • Immunoglobulin G* / blood
  • Immunoglobulin G* / immunology
  • Malaria Vaccines* / immunology
  • Malaria, Vivax* / immunology
  • Malaria, Vivax* / prevention & control
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium vivax* / immunology
  • Poly I-C* / immunology
  • Protozoan Proteins* / genetics
  • Protozoan Proteins* / immunology

Substances

  • Malaria Vaccines
  • Protozoan Proteins
  • Antibodies, Protozoan
  • Poly I-C
  • circumsporozoite protein, Protozoan
  • Aluminum Hydroxide
  • Immunoglobulin G
  • Adjuvants, Immunologic

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by São Paulo Research Foundation (FAPESP) grants awarded to AG (Process 2014/18102-7), HN (Process 2018/14933-2), ES (Process 2017/11931-6), and IS (Process 2012/13032-5) and the National Council for Scientific and Technological Development (CNPq) awarded to ES (Process 304377/2021-0). ES was also supported by PIPAE (2021.1.10424.1.9) and Programa de Apoio aos Novos Docentes grants from the University of São Paulo. IS was also funded by the National Institute of Science and Technology of Vaccines (CNPq 465293/2014-0) and Finep (1208/21). TC-G was a Fapesp (Process 2019/06494-1) and CNPq fellow (Process 162652/2021-6). AF was a Fapesp fellow (Process 2019/25373-0)