Maternal immunization with Group B Streptococcus six‐valent polysaccharide conjugate vaccine supported by lack of toxicity in rat and rabbit fertility and developmental toxicity studies

ABSTRACT The presence of immunoglobulin G (IgG) antibodies against group B streptococcus (GBS) type III polysaccharide (PS) has been correlated with protection against GBS disease. The GBS type III PS is structurally similar to the pneumococcal type 14 PS, differing only in the presence of sialic acid residues. Four different preparations of GBS type III PS were evaluated for their specificity in enzyme-linked immunosorbent assay (ELISA): free PS, free PS mixed with methylated human serum albumin (mHSA), PS conjugated to biotin and PS conjugated to human serum albumin. Three groups of human sera were used to evaluate these PS preparations: sera from recipients of a GBS PS vaccine, sera from women receiving a GBS type III PS-tetanus toxoid conjugate vaccine, and sera from nonimmunized healthy women of childbearing age. Estimated antibody concentrations were different depending on the PS preparation used. Using any of the four preparations, we were able to measure ≤0.05 μg of IgG antibody to the GBS type III PS per ml. The specificity of the assay was determined by competitive inhibition with homologous and heterologous PS. The pneumococcal type 14 PS did not inhibit binding of antibody to the native GBS type III PS in sera from adults receiving the GBS PS vaccine or in sera from nonimmunized adults (except serum G9). The pneumococcal type 14 PS inhibited 50% in sera from recipients of GBS type III conjugate vaccine and in serum G9 when GBS type III PS conjugated to biotin or to HSA was used as antigen in ELISA. These data show that free GBS type III PS or PS mixed with mHSA is a sensitive and specific antigen for ELISA and that conjugation can alter the antigenic specificity of a PS.

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OC 8465 THE DEVELOPMENT OF A CONJUGATE VACCINE AGAINST GROUP B STREPTOCOCCUS: AN AFRICAN PERSPECTIVE

BMJ Global Health ◽

10.1136/bmjgh-2019-edc.18 ◽

2019 ◽

Vol 4 (Suppl 3) ◽

pp. A8.1-A8

Author(s):

Seanette Wilson ◽

Patrick Tippoo

Keyword(s):

South Africa ◽

Clinical Trial ◽

Conjugate Vaccine ◽

Capsular Polysaccharide ◽

Disease Risk ◽

Group B Streptococcus ◽

International Health ◽

Infant Deaths ◽

Young Infants ◽

Group B

BackgroundStreptococcus agalactiae, or group B streptococcus (GBS), is a gram-positive streptococcal bacterium that is well-recognised as one of the leading causes of infant death, particularly in the early neonatal period (the first week of life). An estimated one in five pregnant women around the world carries GBS bacteria in their gastrointestinal or genitourinary tracts and vertical transmission from colonised mothers can lead to invasive disease in their offspring. A recent study conservatively estimated that out of 410,000 GBS cases globally every year, there are at least 1 47 000 stillbirths and infant deaths. Despite being home to only 13% of the world’s population, Africa has the highest GBS disease burden, with 54% of estimated cases and 65% of stillbirths and infant deaths.An effective GBS vaccine, given during pregnancy, is a promising strategy to protect against GBS disease. Currently, no licensed vaccine exists to prevent it, but scientific evaluation of feasibility is favourable. The leading vaccine candidates are capsular polysaccharide-protein conjugate vaccines. Evidence suggests maternal immunisation with a safe and effective GBS vaccine may reduce the disease risk in neonates and young infants.The Biovac Institute was established as a private-public partnership and is the only Southern African vaccine manufacturer. Located in Cape Town, South Africa, Biovac’s mission is to become a leading vaccine developer and producer in South Africa to increase capacity in Africa which only has four other vaccine manufacturers.In collaboration with PATH, an international health organisation, and other partners, Biovac is developing a multivalent conjugate vaccine against GBS. The first stage of the project involves the development of biopharmaceutical manufacturing processes and analytical tests, the preparation of clinical trial product, and execution of a first-in-human clinical trial.This presentation will provide an overview of the project, progress to date, and the path to commercialisation.

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Safety and Immunogenicity of a Second Dose of an Investigational Maternal Trivalent Group B Streptococcus Vaccine in Nonpregnant Women 4–6 Years After a First Dose: Results From a Phase 2 Trial

Clinical Infectious Diseases ◽

10.1093/cid/ciz737 ◽

2019 ◽

Vol 70 (12) ◽

pp. 2570-2579 ◽

Cited By ~ 4

Author(s):

Geert Leroux-Roels ◽

Zourab Bebia ◽

Cathy Maes ◽

Annelies Aerssens ◽

Fien De Boever ◽

...

Keyword(s):

Clinical Trials ◽

Geometric Mean ◽

Group B Streptococcus ◽

Vaccine Dose ◽

Phase 2 ◽

Multiplex Immunoassay ◽

Maternal Immunization ◽

Phase 2 Trial ◽

Group B ◽

Favorable Safety

Abstract Background Maternal immunization against group B streptococcus (GBS) could protect infants from invasive GBS disease. Additional doses in subsequent pregnancies may be needed. We evaluated the safety and immunogenicity of a second dose of an investigational trivalent CRM197-glycoconjugate GBS vaccine (targeting serotypes Ia/Ib/III), administered to nonpregnant women 4–6 years postdose 1. Methods Healthy women either previously vaccinated with 1 dose of trivalent GBS vaccine 4–6 years before enrollment (n = 53) or never GBS vaccinated (n = 27) received a single trivalent GBS vaccine injection. Adverse events (AEs) were recorded. Serotype-specific (Ia/Ib/III) anti-GBS antibodies were measured by multiplex immunoassay prevaccination and 30/60 days postvaccination. Results AEs were reported with similar rates after a first or second dose; none were serious. Of previously GBS-vaccinated women, 92%–98% had anti-GBS concentrations that exceeded an arbitrary threshold (8 µg/mL) for each serotype 60 days postdose 2 vs 36%–56% postdose 1 in previously non–GBS-vaccinated women. Of previously GBS-vaccinated women with undetectable baseline (predose 1) anti-GBS levels, 90%–98% reached this threshold postdose 2. For each serotype, anti-GBS geometric mean concentrations (GMCs) 30/60 days postdose 2 in previously GBS-vaccinated women were ≥200-fold higher than baseline GMCs. Among women with undetectable baseline anti-GBS levels, postdose 2 GMCs in previously GBS-vaccinated women exceeded postdose 1 GMCs in previously non–GBS-vaccinated women (≥7-fold). Conclusions A second trivalent GBS vaccine dose administered 4–6 years postdose 1 was immunogenic with a favorable safety profile. Women with undetectable preexisting anti-GBS concentrations may benefit from a sufficiently spaced second vaccine dose. Clinical Trials Registration NCT02690181

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