Method: After dose-finding studies in 1,050 women, we studied vaccine safety and immunogenicity in a Phase 2 trial in 50 healthy 3rd 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 to 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.
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 .
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