LB19. Progress Toward a Vaccine for Maternal Immunization to Prevent Respiratory Syncytial Virus (RSV) Lower Respiratory Tract Illness (LRTI) in Infants
| Autor: | Pedro A. Piedra, Nita Patel, Greg Glenn, Joyce S Plested, Louis Fries, Gale Smith, D. Nigel Thomas, Iksung Cho |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Vaccine safety Pregnancy business.industry medicine.disease medicine.disease_cause Vaccination Abstracts 03 medical and health sciences 030104 developmental biology Infectious Diseases Respiratory syncytial virus (RSV) medicine.anatomical_structure Oncology Maternal antibody Immunization Immunology medicine Respiratory system C. Late Breaker Abstracts business Respiratory tract |
| Zdroj: | Open Forum Infectious Diseases |
| ISSN: | 2328-8957 |
| DOI: | 10.1093/ofid/ofy229.2193 |
| Popis: | Background RSV is the leading cause of infant LRTI and hospitalization worldwide. The greatest burden of severe disease is in term infants Method After dose-finding studies in 1,050 women, we studied vaccine safety and immunogenicity in a Phase 2 trial in 50 healthy third trimester pregnant women. Safety was assessed in mothers and infants, focusing on pregnancy and peri-partum outcomes. We measured binding and functional RSV antibodies in mothers at baseline, day 14, delivery, and days 35 and 180 post-partum, in cord blood, and in infant sera on days 14, 35, 60, and 180 of life. Anti-F antibody specificities were probed with biolayer interferometry and monoclonal antibodies (mabs) to known epitopes. Result In Phase 2, RSV F nanoparticle vaccine was immunogenic, safe, and well-tolerated in pregnant women. Anti-F IgG and neutralizing antibodies were elicited. Increases in antibodies competitive with mabs to neutralizing epitope sites Ø, VIII, II, and IV, and also the p27 domain displayed by the pre-fusogenic F protein, were present in maternal and infant sera of vaccinated subject pairs. Transplacental transfer of RSV antibodies was more efficient (110 to 120%) in women immunized >30 days before delivery compared with those vaccinated later; RSV antibody t1/2 ranged from 30 to 41 days in infants. We have subsequently enrolled 4,636 pregnant women and their infants in a global observer-blind, randomized, placebo-controlled Phase 3 trial assessing efficacy against medically significant RSV LRTI. In November 2017, an informational analysis performed by an independent statistician, the sponsor remaining blinded, yielded a posterior probability of ≥90% that efficacy was >0%. Conclusion RSV F nanoparticle vaccine is immunogenic in pregnancy, and neutralizing antibodies, including those competing for pre-and post-fusion F epitopes, are transferred efficiently transplacentally. An analysis of Phase 3 efficacy against medically signifcant infant RSV LRTI is projected for Q1, 2019. Disclosures L. Fries, Novavax: Employee and Shareholder, Salary. D. N. Thomas, Novavax: Employee, Salary. G. Smith, Novavax: Employee and Shareholder, Salary. J. Plested, Novavax: Employee, Salary. P. Piedra, Novavax: Collaborator, Consultant, Research Contractor and Scientific Advisor, Consulting fee, contract fees for immunologic assays and Research support. N. Patel, Novavax: Employee and Shareholder, Salary. I. Cho, Novavax: Employee and Shareholder, Salary. G. Glenn, Novavax: Employee and Shareholder, Salary. |
| Databáze: | OpenAIRE |
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