Immunogenicity and Safety of Two Respiratory Syncytial Virus Vaccine Strategies in Lung and Allogeneic Haematopoietic Stem Cell Transplant Recipients.

Condition(s) studied

Investigational drug(s) / intervention(s)

RSVpreF3-AS01: Administration of a single 0.5 mL dose on day 0 (D0) by intramuscular injection

RSVpreF3: Administration of a 0.5 mL dose on day 0 (D0) and a 0.5 mL dose on day 30 by intramuscular injection

Study summary

Respiratory syncytial virus (RSV) is a major cause of acute respiratory infections (ARIs), which occur in seasonal outbreaks. Among the adult population, immunocompromised individuals, particularly lung transplant recipients and recipients of allogeneic haematopoietic stem cell transplants (HSCTs), are at the highest risk of severe ARI. RSV can also cause prolonged inflammation of the airways, leading to persistent deterioration in lung function. Thus, in lung transplant recipients, RSV is a major cause of chronic lung allograft dysfunction (CLAD), the leading cause of lung transplant failure and mortality beyond the first post-transplant year. In recipients of ACSH, RSV infection is associated with the onset and/or worsening of bronchiolitis obliterans syndrome, which leads to increased mortality. Preventing RSV-associated lower respiratory tract disease (LRTD) and its short- and long-term consequences in these populations is therefore a key priority.

Three inactivated RSV vaccines, targeting the RSV fusion glycoprotein in its pre-fusion conformation (RSVpreF), have recently been approved for use in adults. These comprise two recombinant protein vaccines - one with an adjuvant (RSVpreF3-AS01, Arexvy®, GSK) and one without (RSVpreF, Abrysvo®, Pfizer) - and one mRNA vaccine. Although these vaccines have demonstrated their safety, immunogenicity and efficacy (reducing the risk of RSV-related IMRI by approximately 80-85 per cent) in adults aged 60 and over, the pivotal trials excluded immunocompromised patients.

To date, there is limited data on the efficacy, immunogenicity and tolerability of these vaccines in high-risk immunocompromised populations, such as recipients of bone marrow transplants and allogeneic stem cell transplants. Real-world studies suggest that RSV vaccines may reduce the risk of RSV-associated acute respiratory infection and hospitalisations in elderly immunocompromised adults. With regard to immunogenicity, the available cohort studies, conducted on small sample sizes, indicate that the vaccine response is heterogeneous and, overall, lower than that observed in immunocompetent older people. Preliminary data suggest that booster vaccination regimens may be necessary to optimise the immune response in these populations.

Given the significant morbidity associated with RSV in recipients of bone marrow transplants and allogeneic stem cell transplants, it is a priority to assess the immunogenicity and safety profile of RSV vaccines, and to determine the optimal vaccination schedule for these high-risk, immunocompromised populations.

The investigators hypothesise that the immune response to RSV vaccines in severely immunocompromised TP and ACSH recipients is weaker than in immunocompetent older adults, and that enhanced vaccination strategies may be required. In this study, two vaccination strategies will be evaluated in these populations:

* a single dose of the adjuvanted RSVpreF3-AS01 vaccine (Arexvy®),
* or a booster regimen comprising two doses of the non-adjuvanted RSVpreF vaccine (Abrysvo®), administered one month apart.

Eligibility

Primary outcome measure(s)

• RSVpreF-binding antibody response to each of the two RSV vaccine strategies in two distinct subcohorts (LTR and HSCTR) — One month after completing vaccination (Visit 2 - Day 30 for patients with RSVpreF3-AS01 or Day 60 for patients with RSVApreF3)
  Proportion of participants in each group who achieve a seroresponse one month after completion of vaccination (visit 2). A seroresponse is defined as either (1) seroconversion, i.e., an RSVpreF-binding serum IgG concentration ≥4 times the lower limit of quantification (LLOQ) when baseline is \<LLOQ, or (2) a ≥4-fold rise in RSVpreF-binding serum IgG concentration from baseline

Trial sites (16)

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