GSK's Maternal RSV Vaccine Enters Phase 3 Clinical Trial: Rapidly Induces Robust Immunity

November 23, 2020 /Bio ValleyBIOON/ --GlaxoSmithKline(GSK) recently announced that the Phase 3 GRACE study (NCT04605159), evaluating the safety and efficacy of its respiratory syncytial virus (RSV) candidate vaccine for maternal immunization (GSK3888550A vaccine), has begun vaccinating participants.

GRACE is a double-blind Phase 3 study that will be conducted in 10,000 pregnant women aged 18–49 years to evaluate the efficacy of a single-dose intramuscular administration of an unadjuvanted maternal RSV vaccine in preventing RSV-associated lower respiratory tract infection (LRTI) in neonates among healthy pregnant women aged 18–49 years. The study will also assess the safety of this vaccine in vaccinated mothers and their infants. The study is expected to conclude in early 2024, with interim results anticipated in the second half of 2022.

Respiratory syncytial virus (RSV) is the leading cause of respiratory tract infections in infants and young children, such as bronchiolitis (inflammation and congestion of the small airways or bronchioles in the lungs) and viral pneumonia (an inflammatory condition of the small air sacs or alveoli in the lungs). Currently, there are no vaccines available for RSV. It is estimated that globally, 33 million cases of RSV occur annually in children under five years of age, with approximately 3 million hospitalizations and around 120,000 deaths due to infection-related complications. RSV-associated lower respiratory tract infections (LRTI) carry significant morbidity and mortality among infants under six months of age, with nearly half of pediatric hospitalizations (approximately 1.4 million cases) and deaths occurring in this age group.

Emmanuel Hanon, Senior Vice President and Head of Vaccine R&D at GSK, stated: “The burden of RSV in young children is substantial. A vaccine capable of protecting them from its effects would represent a significant advancement in addressing the RSV burden, preventing infant illness and family distress, and alleviating the associated societal burden. Advancing our RSV candidate vaccine portfolio based on robust available data is a critical step toward achieving GSK’s goal of reducing the global burden of RSV-associated disease.”

RSV also poses a significant threat to the health of older adults. In the United States alone, there are 177,000 RSV-associated hospitalizations and 14,000 deaths annually. As the population ages, the incidence and mortality rates of respiratory infections, including RSV, will steadily increase.

Last month, GSK announced positive Phase I/II data on the safety, reactogenicity, and immunogenicity of its RSV vaccines for maternal immunization (GSK3888550A vaccine) and older adult immunization (GSK3844766A vaccine).

Both candidate vaccines contain the recombinant subunit prefusion RSV antigen (RSVPreF3), which is believed to trigger the desired immune response. The vaccine for older adults also includes GSK’s proprietary AS01 adjuvant system to enhance the immune response, as this population tends to have a weaker immune response to vaccination compared to younger individuals.

Maternal RSV candidate vaccines were tested in 502 healthy, non-pregnant adults, comparing three different doses of the RSV candidate vaccine against placebo, with monthly visits (on days 8, 31, and 91 post-immunization). The data showed that, compared to baseline: (1) the candidate vaccine rapidly boosted pre-existing immunity at all dose levels, resulting in high levels of protective neutralizing antibodies; (2) on day 8, a 14-fold increase in neutralizing antibody titers against RSV-A and RSV-B was observed. Initial data from pregnant women will be released in 2021.

The candidate vaccine for the elderly was first tested in 48 healthy adults (aged 18–40 years) and then in 1,005 healthy older adults (aged 60–80 years), using different doses of antigen and adjuvant, and compared with placebo. Interim data one month after immunization showed: (1) the candidate vaccine induced robust humoral and cellular immune responses compared to baseline; (2) protective antibodies (RSVPreF3-IgG and RSV-A neutralizing antibodies) increased nearly 10-fold in the vaccinated group; (3) importantly, cellular immunity (RSVPreF3-specific CD4+ T cells) was enhanced in vaccinated older adults, reaching levels similar to those observed in younger adults, despite lower initial baseline levels in the elderly population.

These two vaccines are part of GSK’s RSV vaccine program, which features three RSV candidate vaccines tailored to different populations (maternal, pediatric, and older adult vaccines) and utilizes distinct novel technologies to protect the most vulnerable groups heavily impacted by the disease: infants and older adults. All three candidate vaccines have received U.S.FDAFast Track Designation (FTD)

RSV vaccines can significantly reduce disease incidence, medical visits, and hospitalization rates among infants, young children, and the elderly, thereby exerting a substantial impact on the health and healthcare costs of the most vulnerable populations worldwide. Based on existing data and interactions with regulatory authorities, Phase 3 studies of RSV candidate vaccines for the elderly are scheduled to launch in the coming months, while Phase I/II trials (in RSV-negative infants) and Phase II trials (in RSV-seropositive infants) of pediatric RSV candidate vaccines are still ongoing. (Bioon.com)

Original Source: GSK starts phase 3 study of RSV maternal candidate vaccine