Poly(I:C) adjuvant strongly enhances parasite-inhibitory antibodies and Th1 response against Plasmodium falciparum merozoite surface protein-1 (42-kDa fragment) in BALB/c mice

Med Microbiol Immunol. 2018 Apr;207(2):151-166. doi: 10.1007/s00430-018-0535-4. Epub 2018 Feb 3.

Abstract

Malaria vaccine development has been confronted with various challenges such as poor immunogenicity of malaria vaccine candidate antigens, which is considered as the main challenge. However, this problem can be managed using appropriate formulations of antigens and adjuvants. Poly(I:C) is a potent Th1 inducer and a human compatible adjuvant capable of stimulating both B- and T-cell immunity. Plasmodium falciparum merozoite surface protein 142 (PfMSP-142) is a promising vaccine candidate for blood stage of malaria that has faced several difficulties in clinical trials, mainly due to improper adjuvants. Therefore, in the current study, poly(I:C), as a potent Th1 inducer adjuvant, was evaluated to improve the immunogenicity of recombinant PfMSP-142, when compared to CFA/IFA, as reference adjuvant. Poly(I:C) produced high level and titers of anti-PfMSP-142 IgG antibodies in which was comparable to CFA/IFA adjuvant. In addition, PfMSP-142 formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-4 (23.9) and IgG2a/IgG1 (3.77) with more persistent, higher avidity, and titer of IgG2a relative to CFA/IFA, indicating a potent Th1 immune response. Poly(I:C) could also help to induce anti-PfMSP-142 antibodies with higher growth-inhibitory activity than CFA/IFA. Altogether, the results of the current study demonstrated that poly(I:C) is a potent adjuvant that can be appropriate for being used in PfMSP-142-based vaccine formulations.

Keywords: Growth-inhibitory antibody; MSP-1; Malaria vaccine; Plasmodium falciparum; Poly(I:C) adjuvant.

Publication types

  • Comparative Study

MeSH terms

  • Adjuvants, Immunologic / administration & dosage*
  • Animals
  • Antibodies, Protozoan / blood*
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Interleukin-4 / metabolism
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology*
  • Merozoite Surface Protein 1 / administration & dosage
  • Merozoite Surface Protein 1 / immunology*
  • Mice, Inbred BALB C
  • Plasmodium falciparum / immunology*
  • Poly I-C / administration & dosage*
  • Th1 Cells / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / immunology

Substances

  • Adjuvants, Immunologic
  • Antibodies, Protozoan
  • Immunoglobulin G
  • Malaria Vaccines
  • Merozoite Surface Protein 1
  • Vaccines, Synthetic
  • Interleukin-4
  • Interferon-gamma
  • Poly I-C