Serum alpha-mannosidase as an additional barrier to eliciting oligomannose-specific HIV-1-neutralizing antibodies.
Sci Rep
; 10(1): 7582, 2020 05 05.
Article
em En
| MEDLINE
| ID: mdl-32371950
ABSTRACT
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.
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article