GSK presents positive clinical data on maternal and older adults RSV candidate vaccines

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GSK announced that its Respiratory Syncytial Virus (RSV) candidate vaccines for maternal immunisation (GSK3888550A) and older adults (GSK3844766A) were well-tolerated and highly immunogenic in Phase I/II clinical studies. The data were presented virtually at the ID Week Congress.

RSV is a leading cause of respiratory infections such as bronchiolitis (inflammation and congestion of the small airways or bronchioles of the lung) and pneumonia (an inflammatory condition of the lung small air sacs or alveoli) in infants and older adults. It is estimated to cause about 3 million hospitalisations of children under 5 year of age globally[1], and 177,000 hospitalisations of older people in the US alone[2].

Both candidate vaccines contain a recombinant subunit pre-fusion RSV antigen (RSVPreF3) which is believed to trigger the required immune response. The vaccine for older adults also includes GSK’s proprietary AS01 adjuvant system[3] to boost the immune response as this population tends to show weaker immune response to vaccination than younger adults.

The vaccine candidate for older adults was first tested in 48 healthy adults (18-40 years old) and then in 1,005 healthy older adults (60-80 years old) with different dosages of antigen and adjuvant compared with a placebo. The interim data 1-month post-immunisation show that:

the candidate vaccine elicited a robust humoral and cellular immunity compared with baseline
a close to 10 times increase of protective antibodies (RSVPreF3 IgG and RSV-A neutralising antibodies) was induced in the vaccinated group importantly, the cellular immunity (RSVPreF3-specific CD4+ T-cells) of the vaccinated older adults was boosted to reach similar range to that observed in the younger adults after vaccination with the non-adjuvanted formulation, despite the initial lower baseline level observed in older adults compared with young adults.

The maternal RSV candidate vaccine was tested with 3 different doses compared with placebo in 502 healthy non-pregnant women over monthly visits (Day 8, Day 31 and Day 91 post immunisation). The data show that, compared with baseline:

the investigational vaccine was able to rapidly boost the pre-existing immunity at all dose levels, leading to high levels of protective neutralising antibodies
at Day 8, a 14-fold increase in RSV-A and RSV-B neutralising antibodies titers was observed.

These two vaccines are part of a tailored, portfolio approach GSK is pursuing with three RSV candidate vaccines – maternal, paediatric and older adults – using different novel technologies aiming to help protect the populations most impacted: infants and older adults. All three candidate vaccines have received FDA fast-track designation.

Emmanuel Hanon, Senior Vice-President and Head of Vaccines R&D, said: “RSV is an infectious disease that can have a very serious impact on families and societies. We are delighted to see these positive results confirming our approach to develop dedicated vaccines building on the strategic use of our platform technologies for the populations most at risk from RSV infections – young infants and older adults. Our portfolio strategy takes into account the unique needs of the immune system of these vulnerable populations and we look forward to progressing these assets to Phase III trials to evaluate their potential efficacy”.

Vaccines for RSV prevention could lead to significant reductions in disease, doctor’s visits, and hospitalisations in infants, toddlers, and older adults, thus having the potential for a significant benefit to individual health in the most vulnerable populations as well as a positive impact on the burden and costs of healthcare systems around the world.

Based on available data and engagement with regulators, Phase III studies for both older adults and maternal RSV candidate vaccines are in preparation and on-track to start in the coming months, while the Phase I/II (in RSV-seronegative infants) and Phase II (in RSV-seropositive infants) studies with the paediatric RSV candidate vaccine are ongoing. Phase I/II safety and immunogenicity data on the paediatric RSV candidate vaccine in RSV-seropositive infants will be presented at European Society for Paediatric Infectious Diseases (ESPID) on 26-29 October 2020.

About GSK’s RSV candidate vaccine for older adults (GSK3844766A)

The Phase I/II study investigates the safety, reactogenicity and immune response of GSK’s RSV candidate vaccine in older adults aged 60 to 80 (NCT03814590). This candidate vaccine contains GSK’s proprietary AS01 adjuvant, which is also used in GSK’s shingles vaccine. The safety, reactogenicity and immune responses (humoral and cellular-mediated) were first assessed in 48 healthy adults aged 18–40 years who were vaccinated with either 30, 60 or 120 μg dose level of RSVPreF3 non-adjuvanted vaccine or placebo. Following favourable safety outcomes, 1005 adults aged 60–80 years were randomised in a 2-step staggered manner to receive 1 of the 9 RSV vaccine formulations containing either 30, 60 or 120 μg dose level of RSVPreF3, non-adjuvanted or adjuvanted with AS01E or AS01B, or placebo.

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