Format

Send to

Choose Destination
J Infect Dis. 2019 Feb 19. pii: jiz062. doi: 10.1093/infdis/jiz062. [Epub ahead of print]

A novel hexavalent capsular polysaccharide conjugate vaccine (GBS6) for the prevention of neonatal group B streptococcal infections by maternal immunization.

Author information

1
Vaccine Research and Development, Pfizer Inc., Pearl River, NY, USA.

Abstract

BACKGROUND:

Group B streptococcus (GBS) causes serious diseases in newborn infants, often resulting in lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early and late onset disease and maternal complications potentially could be addressed.

METHODS:

Capsular polysaccharide conjugate vaccine GBS6 was designed using Whole Genome Sequencing surveillance data of recent, global GBS isolates responsible for invasive neonatal GBS disease. Capsular polysaccharides were isolated, oxidized using sodium periodate and conjugated to CRM197 by reductive amination in dimethyl sulfoxide. Immune responses in mice and rhesus macaques were measured in a multiplex Luminex IgG assay and opsonophagocytic activity assays.

RESULTS:

The optimized conjugates were immunogenic, alone and in combination, in mice and rhesus macaques, inducing IgG antibodies that mediated opsonophagocytic killing. Active immunization of murine dams with GBS6 prior to mating resulted in serotype-specific protection of pups from a lethal challenge with group B streptococcus. Protection following passive administration of serotype-specific IgG monoclonal antibodies to dams demonstrated conclusively that anti-capsular polysaccharide IgG alone is sufficient for protection.

CONCLUSIONS:

The findings support the ongoing clinical evaluation of maternal GBS6 vaccination as a potential alternative prevention method of GBS disease in infants.

KEYWORDS:

Streptococcus agalactiae ; CRM197; GBS6; capsular polysaccharide; conjugate; group B streptococcus; maternal vaccine

PMID:
30778554
DOI:
10.1093/infdis/jiz062

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center