Colloidal Manganese Salt Improves the Efficacy of Rabies Vaccines in Mice, Cats, and Dogs

J Virol. 2021 Nov 9;95(23):e0141421. doi: 10.1128/JVI.01414-21. Epub 2021 Sep 8.


Rabies, caused by rabies virus (RABV), remains a serious threat to public health in most countries worldwide. At present, the administration of rabies vaccines has been the most effective strategy to control rabies. Herein, we evaluate the effect of colloidal manganese salt (Mn jelly [MnJ]) as an adjuvant of rabies vaccine in mice, cats, and dogs. The results showed that MnJ promoted type I interferon (IFN-I) and cytokine production in vitro and the maturation of dendritic cells (DCs) in vitro and in vivo. Besides, MnJ serving as an adjuvant for rabies vaccines could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, plasma cells (PCs), and RABV-specific antibody-secreting cells (ASCs), consequently improve the immunogenicity of rabies vaccines, and provide better protection against virulent RABV challenge. Similarly, MnJ enhanced the humoral immune response in cats and dogs as well. Collectively, our results suggest that MnJ can facilitate the maturation of DCs during rabies vaccination, which can be a promising adjuvant candidate for rabies vaccines. IMPORTANCE Extending the humoral immune response by using adjuvants is an important strategy for vaccine development. In this study, a novel adjuvant, MnJ, supplemented in rabies vaccines was evaluated in mice, cats, and dogs. Our results in the mouse model revealed that MnJ increased the numbers of mature DCs, Tfh cells, GC B cells, PCs, and RABV-specific ASCs, resulting in enhanced immunogenicity and protection rate of rabies vaccines. We further found that MnJ had the same stimulative effect in cats and dogs. Our study provides the first evidence that MnJ serving as a novel adjuvant of rabies vaccines can boost the immune response in both a mouse and pet model.

Keywords: adjuvant; colloidal manganese salt; dendritic cells; rabies vaccine; rabies virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Antibodies, Viral / blood
  • Antibody-Producing Cells / immunology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes
  • Cats
  • Dendritic Cells / immunology
  • Disease Models, Animal
  • Dogs
  • Female
  • Germinal Center / immunology
  • Immunity, Humoral
  • Manganese / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Plasma Cells / immunology
  • Rabies / immunology
  • Rabies Vaccines / immunology*
  • Rabies virus / immunology
  • Vaccination
  • Vaccine Development


  • Adjuvants, Immunologic
  • Antibodies, Viral
  • Rabies Vaccines
  • Manganese