Safety and Immunogenicity of an Investigational Respiratory Syncytial Virus Vaccine (RSVPreF3) in Mothers and Their Infants: A Phase 2 Randomized Trial

Abstract

Background In a phase I/II study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. Methods In this phase II observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18-40-year-old healthy pregnant women through six months post-delivery and their offspring through infancy; immunogenicity was evaluated through day 43 post-delivery and day 181 post-birth, respectively. Results RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo-related. In the 60 and 120 µg RSVPreF3 groups: (i) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, one month post-vaccination and remained 8.9–10.0-fold over pre-vaccination at day 43 post-delivery, (ii) nAb titers were consistently higher compared to placebo recipients, (iii) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (iv) nAb levels in infants were highest at birth and declined through day 181 post-birth. Conclusions RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns.

Respiratory syncytial virus infection in the modern era

“…Later analysis of samples collected during clinical trials conducted with DS-Cav1 and MEDI7510 (a vaccine candidate containing RSV post-F) showed that DS-Cav1 induced antibodies that more potently neutralized both RSV-A and -B strains due to targeting of antigenic sites which are only present on the pre-F protein [32 ▪ ]. Another subunit vaccine candidate (RSVPreF3) has been developed by GlaxoSmithKline Biologicals (GSK) and assessed in a Phase 2 clinical trial (NCT04126213) in pregnant women (18–40 years) [33] and a Phase 3 clinical trial (NCT04886596) in older adults (≥60 years) (34). Inoculation of pregnant women with RSVPreF3 during the late second or third trimester induced high levels of neutralizing antibodies against both RSV-A and RSV-B subtypes leading to transfer of maternal RSV-specific antibodies to infants, which persisted until at least 6 months post-birth [33].…”

“…Another subunit vaccine candidate (RSVPreF3) has been developed by GlaxoSmithKline Biologicals (GSK) and assessed in a Phase 2 clinical trial (NCT04126213) in pregnant women (18–40 years) [33] and a Phase 3 clinical trial (NCT04886596) in older adults (≥60 years) (34). Inoculation of pregnant women with RSVPreF3 during the late second or third trimester induced high levels of neutralizing antibodies against both RSV-A and RSV-B subtypes leading to transfer of maternal RSV-specific antibodies to infants, which persisted until at least 6 months post-birth [33]. An efficacy of 94.1% against severe RSV-induced LRTI and 71.7% against RSV-related acute respiratory infection was observed in older adults inoculated with RSVPreF3 [34 ▪▪ ].…”

Review and Update of Active and Passive Immunization Against Respiratory Syncytial Virus

“…Preliminary data released by Pfizer reported a vaccine efficacy of 81.8% (99% CI 40.6–96.3) against severe medically attended LRTI due to RSV from birth to 90 days of life and 69.4% (99% CI 44.3–84.1) up to 6 months [ 132 ]. GSK recently reported data from a phase II observer-blind, placebo-controlled RCT (NCT04126213) [ 133 ]. An RSVPreF3 maternal vaccine administered to 213 pregnant women aged 18–40 years during the second or third trimester was well tolerated.…”

Respiratory viral infections including COVID-19 in solid organ transplantation

“…Currently, there are only two RSV vaccines approved by the US Food and Drug Administration and studies in SOT are underway, summarized in Table 6 along with investigational vaccines and other passive immunization agents against RSV currently undergoing development [80,83–94].…”

“…Recent trials show benefit against medically attended RSV-associated LRI in at-risk preterm and healthy late preterm and term infants [81,82]. Currently, there are only two RSV vaccines approved by the US Food and Drug Administration and studies in SOT are underway, summarized in Table 6 along with investigational vaccines and other passive immunization agents against RSV currently undergoing development [80,[83][84][85][86][87][88][89][90][91][92][93][94].…”