title: Considerations for a phase-III trial to evaluate a group B Streptococcus polysaccharide-protein conjugate vaccine in pregnant women for the prevention of early- and late-onset invasive disease in young-infants.
abstract: In 2010, an estimated 393,000 infection-related neonatal deaths occurred worldwide with Group B streptococcus (GBS) being a leading cause. Prevention of early-onset disease (0-6 days; EOD) is currently focused on intra-partum antibiotic prophylaxis to mothers identified as being at risk; such strategies reduce EOD by 75-80% but are resource-intensive and logistically-difficult to implement in developing countries. Vaccination of pregnant women is an alternate strategy for preventing both EOD and late-onset disease (7-89 days; LOD). A trivalent GBS polysaccharide-protein conjugate vaccine (GBS-CV) composed of capsular epitopes from serotypes Ia, Ib and III is undergoing phase-II evaluation among pregnant women in Europe, North America and Africa. These serotypes cause 70-80% of all invasive GBS disease in early-infancy. Maternal anti-GBS antibodies are associated with protection from EOD, however, since a correlate of efficacy has not been defined, a phase III efficacy trial may be required for licensure. Criteria for selecting appropriate sites include sufficiently high GBS incidence in large birth cohorts, as well as adequate clinical and microbiological diagnostic skills and capacities. Alternate pathways to licensure should be explored, e.g. identification of serological correlates of protection with subsequent phase IV studies establishing vaccine-effectiveness against invasive GBS disease. Conducting a randomized, placebo-controlled efficacy trial, however, has the additional advantage of also being able to evaluate the role of GBS contributing to neonatal culture-negative sepsis, stillbirths, prematurity and low-birth weight.
authors: National Institute for Communicable Diseases, Division of National Health Laboratory Service, Centre for Vaccines and Immunology, Sandringham, South Africa. madhis@rmpru.co.za
authors: Shabir A
authors: SA
authors: Madhi
authors: Ziyaad
authors: Z
authors: Dangor
authors: Paul T
authors: PT
authors: Heath
authors: Stephanie
authors: S
authors: Schrag
authors: Alaine
authors: A
authors: Izu
authors: Ajoke
authors: A
authors: Sobanjo-Ter Meulen
authors: Peter M
authors: PM
authors: Dull
mesh_terms: D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control; D013290:Streptococcal Infections / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000627:therapeutic use*; D013292:Streptococcus agalactiae / Q000145:classification; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000627:therapeutic use
chemical_list: D022541:Streptococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Conjugate vaccine; Group B streptococcus; Pregnant women