Serum alpha-mannosidase as an additional barrier to eliciting oligomannose-specific HIV-1-neutralizing antibodies

Sci Rep. 2020 May 5;10(1):7582. doi: 10.1038/s41598-020-64500-8.


Oligomannose-type glycans on HIV-1 gp120 form a patch that is targeted by several broadly neutralizing antibodies (bnAbs) and that therefore is of interest to vaccine design. However, attempts to elicit similar oligomannose-specific bnAbs by immunizing with oligomannosidic glycoconjugates have only been modestly successful so far. A common assumption is that eliciting oligomannose-specific bnAbs is hindered by B cell tolerance, resulting from the presented oligomannosides being sensed as self molecules. Here, we present data, along with existing scientific evidence, supporting an additional, or perhaps alternate, explanation: serum mannosidase trimming of the presented oligomannosides in vivo. Mannosidase trimming lessens the likelihood of eliciting antibodies with capacity to bind full-sized oligomannose, which typifies the binding mode of existing bnAbs to the oligomannose patch. The rapidity of the observed trimming suggests the need for immunization strategies and/or synthetic glycosides that readily avoid or resist mannosidase trimming upon immunization and can overcome possible tolerance restrictions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AIDS Vaccines / immunology
  • Animals
  • Antibodies, Neutralizing / immunology*
  • Bacterial Proteins / immunology
  • Epitopes / immunology
  • Female
  • Glycoconjugates
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • HIV Antibodies / immunology*
  • HIV Infections / blood*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1 / immunology*
  • Humans
  • Male
  • Mice
  • Oligosaccharides
  • Polysaccharides / immunology
  • Protein Binding
  • Protein Multimerization
  • Vaccines, Conjugate
  • alpha-Mannosidase / blood*
  • env Gene Products, Human Immunodeficiency Virus / chemistry
  • env Gene Products, Human Immunodeficiency Virus / immunology


  • AIDS Vaccines
  • Antibodies, Neutralizing
  • Bacterial Proteins
  • Epitopes
  • Glycoconjugates
  • Glycoproteins
  • HIV Antibodies
  • Oligosaccharides
  • Polysaccharides
  • Vaccines, Conjugate
  • env Gene Products, Human Immunodeficiency Virus
  • oligomannoside
  • CRM197 (non-toxic variant of diphtheria toxin)
  • alpha-Mannosidase