Speaker

Natalie Silmon de Monerri

Natalie Silmon de Monerri

Associate Director, Bacterial Vaccines & Technology

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Dr. Silmon de Monerri is a microbiologist with >15 years of experience in basic research in infectious diseases. Dr. Silmon de Monerri received her undergraduate Master’s degree in Molecular and Cellular Biology from the University of Bath, United Kingdom. During her undergraduate years, she developed a passion for infectious diseases and protein biochemistry, while focusing on Staphylococcus aureus mechanisms of immune evasion. She received her PhD in Infection and Immunity in 2010 from the MRC National Institute for Medical Research in London, United Kingdom, which focused on proteases that regulate the malaria parasite life cycle. In 2011, Dr. Silmon de Monerri moved to New York for her postdoctoral training at Albert Einstein College of Medicine, which focused on posttranslational modifications and epigenetic regulation using molecular and systems biology approaches in the parasite Toxoplasma gondii.
Dr. Silmon de Monerri joined Pfizer in 2017 to focus on microbial genomics and transcriptional regulation in bacterial pathogens. She has been the Molecular Biology / Microbiology team lead for Bacterial Vaccines since 2018, and leads a team of bench scientists focused on early-stage vaccine antigen development and preclinical research. Dr. Silmon de Monerri is the Research Scientific Lead for the Group B Streptococcus vaccine program, where she is responsible for leading scientific strategy as well as internal and external research projects and to support licensure of the Pfizer GBS vaccine candidate.

Potential efficacy of a maternal GBS vaccine to prevent invasive GBS disease in infants

Background/ hypothesis

Natural history studies have correlated group B streptococcus (GBS) serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with reduced risk of GBS disease in early life. Hexavalent CPS glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive GBS in young infants.
Methods

C1091002 is an ongoing phase 2, placebo-controlled, study in pregnant women, assessing the safety and immunogenicity of a single dose of various GBS6 formulations with analysis of maternally transferred anti-CPS antibodies. Data is presented from participants in South Africa. A parallel seroepidemiology study in the same population assessed anti CPS IgG concentrations in infant sera associated with risk of invasive disease. A similar seroepidemiology study was undertaken in Finland.

Results
In both studies, naturally acquired anti-CPS IgG concentrations correlates well with reduced risk of disease. GBS6 induces a robust maternal antibody response to all six vaccine serotypes, with a measurable transplacental transfer of anti-CPS IgG. Natural immunity anti-CPS IgG levels, associated with a >80% risk reduction of invasive GBS disease, were used to predict the efficacy of maternally transferred (GBS6-induced) antibody levels.

Conclusion
This first evaluation of the GBS6 vaccine in pregnant women demonstrates that it induces antibodies transferred to infants at levels associated with a significant reduced risk of infant invasive GBS disease, based on natural immunity studies.

Development and Validation of a 6-plex Luminex Assay for Measuring Human Serum Antibodies to GBS

Six serotypes (Ia, Ib, II, III, IV, and IV) cause nearly all group B streptococcal (GBS) disease globally. Several studies have shown that anti-capsular polysaccharide IgG concentration is associated with risk of invasive GBS disease, however the lack of a standardized assay to measure anti-CPS IgG has precluded comparison of protective antibody concentrations across these studies, or to immunogenicity data from capsular polysaccharide conjugate vaccine clinical trials. A multiplex Luminex-based direct immunoassay (dLIA) has been developed to simultaneously measure the concentration of serum IgG specific for the six prevalent GBS CPS serotypes. The assay uses poly-L-lysine (PLL)-conjugated CPS that is chemically coupled to spectrally distinct Luminex microspheres. Assay validation was performed using serum samples obtained from human subjects vaccinated with an investigational 6-valent GBS CPS conjugate vaccine. Assay results are expressed as IgG concentrations (µg/mL) using a human serum reference standard composed of pooled sera from vaccinated subjects. Weight-based IgG assignments were established using surface plasmon resonance (SPR) to generate a homologous calibrator for calibration in the dLIA. The lower limits of quantitation (LLOQ) for all serotypes covered in the 6-plex GBS IgG dLIA fell within the range of 0.002-0.022 µg/mL IgG. Taken together, the 6-plex GBS IgG dLIA platform is specific for six GBS serotypes included in Pfizer’s investigational vaccine, has a wide dilution adjusted assay range and is precise (<18.5% relative standard deviation) for all serotypes. The 6-plex GBS IgG dLIA permits direct cross-serotype comparison of CPS-specific IgG, and in combination with the validation presented in this work, positions the assay as a powerful tool to serve as the primary serological readout for global seroepidemiology studies and vaccine clinical trials.

Natalie Silmon de Monerri

Associate Director, Bacterial Vaccines & Technology

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