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Maternal RSV nanoparticle vaccine transfers antibodies through placenta

Pedro Piedra
Pedro A. Piedra

SAN FRANCISCO — A respiratory syncytial virus F nanoparticle vaccine was immunogenic in pregnant women and elicited antibodies that were transferred efficiently through the placenta to infants, according to research presented at IDWeek. The results have led to a landmark, ongoing phase 3 study, according to researchers.

Pedro A. Piedra, MD, a professor of virology, microbiology and pediatrics at Baylor College of Medicine, and colleagues reported that RSV is the leading cause of infant lower respiratory tract infection (LRTI) and hospitalization throughout the world, with the greatest burden of severe disease experienced by infants aged younger than 5 months.

The researchers reported that Novavax is developing an aluminum adjuvanted RSV-F nanoparticle vaccine for women in the third trimester of pregnancy to prevent infant RSV LRTI in the first 3 to 6 months of life. The vaccine works via transplacental transfer of the maternal antibodies.

The vaccine “represents the first potential opportunity to prevent RSV disease in infants,” Gregory M. Glenn, MD, president of research and development at Novavax, told Infectious Diseases in Children in a previous interview. “The lack of effective treatments for RSV necessitates a focus on protecting infants from birth through the first months of their life. Maternal immunization offers the best method of protection from RSV disease in infants under 6 months of age.”

Piedra , Glenn and colleagues conducted a phase 2 study of 50 healthy women in their third trimester of pregnancy, following previous dose-finding studies in 1,050 women. They focused on safety during pregnancy and peripartum outcomes in both mothers and infants. Piedra and colleagues measured binding and functional RSV antibodies at baseline, day 14, delivery and days 35 and 180 postpartum in mothers, as well as in cord blood and on days 14, 35, 60 and 180 of life in infant sera.

They reported that the RSV F nanoparticle vaccine in pregnant women was immunogenic, safe and well-tolerated, and that the women produced anti-F IgG and neutralizing antibodies.

Maternal and infant sera of those who were vaccinated showed increases in antibodies that were competitive with monoclonal antibodies displayed by the pre-fusogenic F protein. These antibodies targeted antigenic sites unique to the pre-fusion F conformation and to shared antigenic sites in both the pre-fusion and post-fusion conformations. The researchers reported that women who were immunized more than 30 days before delivery experienced a more efficient (110% to 120%) transplacental transfer of RSV antibodies compared with women who were vaccinated later.

Piedra and colleagues subsequently enrolled 4,636 pregnant women and their infants for a randomized, placebo-controlled phase 3 study measuring efficacy against medically significant RSV LRTI. The researchers said that they expect to announce results of a phase 3 efficacy analysis in the first quarter of 2019.

“The phase 3 maternal immunization study to prevent severe RSV LRTI in infants is a landmark study,” Piedra told Infectious Diseases in Children. “It is the first phase 3 trial of an RSV vaccine for the prevention of severe RSV disease in infants in over 60 years since the discovery of RSV. I am cautiously optimistic that the broad breath of antibody response induced by the RSV-F nanoparticle vaccine in pregnant women, the efficient transplacental transfer of functional antibodies to the infants, and the excellent vaccine safety profile to date will translate to a well-tolerated vaccine with a high level of efficacy against severe RSV disease in infants during their first 90 to 150 days of life.” – by Bruce Thiel

Reference:

Fries L, et al. Abstract LB19. Presented at: IDWeek; Oct. 3-7, 2018; San Francisco.

Disclosures: Piedra reports serving as a collaborator, consultant, research contractor and scientific adviser to Novavax. Glenn reports being an employee and shareholder of Novavax. Please see the abstract for all other authors’ relevant financial disclosures.

Pedro Piedra
Pedro A. Piedra

SAN FRANCISCO — A respiratory syncytial virus F nanoparticle vaccine was immunogenic in pregnant women and elicited antibodies that were transferred efficiently through the placenta to infants, according to research presented at IDWeek. The results have led to a landmark, ongoing phase 3 study, according to researchers.

Pedro A. Piedra, MD, a professor of virology, microbiology and pediatrics at Baylor College of Medicine, and colleagues reported that RSV is the leading cause of infant lower respiratory tract infection (LRTI) and hospitalization throughout the world, with the greatest burden of severe disease experienced by infants aged younger than 5 months.

The researchers reported that Novavax is developing an aluminum adjuvanted RSV-F nanoparticle vaccine for women in the third trimester of pregnancy to prevent infant RSV LRTI in the first 3 to 6 months of life. The vaccine works via transplacental transfer of the maternal antibodies.

The vaccine “represents the first potential opportunity to prevent RSV disease in infants,” Gregory M. Glenn, MD, president of research and development at Novavax, told Infectious Diseases in Children in a previous interview. “The lack of effective treatments for RSV necessitates a focus on protecting infants from birth through the first months of their life. Maternal immunization offers the best method of protection from RSV disease in infants under 6 months of age.”

Piedra , Glenn and colleagues conducted a phase 2 study of 50 healthy women in their third trimester of pregnancy, following previous dose-finding studies in 1,050 women. They focused on safety during pregnancy and peripartum outcomes in both mothers and infants. Piedra and colleagues measured binding and functional RSV antibodies at baseline, day 14, delivery and days 35 and 180 postpartum in mothers, as well as in cord blood and on days 14, 35, 60 and 180 of life in infant sera.

They reported that the RSV F nanoparticle vaccine in pregnant women was immunogenic, safe and well-tolerated, and that the women produced anti-F IgG and neutralizing antibodies.

Maternal and infant sera of those who were vaccinated showed increases in antibodies that were competitive with monoclonal antibodies displayed by the pre-fusogenic F protein. These antibodies targeted antigenic sites unique to the pre-fusion F conformation and to shared antigenic sites in both the pre-fusion and post-fusion conformations. The researchers reported that women who were immunized more than 30 days before delivery experienced a more efficient (110% to 120%) transplacental transfer of RSV antibodies compared with women who were vaccinated later.

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Piedra and colleagues subsequently enrolled 4,636 pregnant women and their infants for a randomized, placebo-controlled phase 3 study measuring efficacy against medically significant RSV LRTI. The researchers said that they expect to announce results of a phase 3 efficacy analysis in the first quarter of 2019.

“The phase 3 maternal immunization study to prevent severe RSV LRTI in infants is a landmark study,” Piedra told Infectious Diseases in Children. “It is the first phase 3 trial of an RSV vaccine for the prevention of severe RSV disease in infants in over 60 years since the discovery of RSV. I am cautiously optimistic that the broad breath of antibody response induced by the RSV-F nanoparticle vaccine in pregnant women, the efficient transplacental transfer of functional antibodies to the infants, and the excellent vaccine safety profile to date will translate to a well-tolerated vaccine with a high level of efficacy against severe RSV disease in infants during their first 90 to 150 days of life.” – by Bruce Thiel

Reference:

Fries L, et al. Abstract LB19. Presented at: IDWeek; Oct. 3-7, 2018; San Francisco.

Disclosures: Piedra reports serving as a collaborator, consultant, research contractor and scientific adviser to Novavax. Glenn reports being an employee and shareholder of Novavax. Please see the abstract for all other authors’ relevant financial disclosures.

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