A Phase 3, observer-blind, randomized, placebo controlled study to evaluate the non inferiority of the immune response and safety of the RSVPreF3 OA investigational vaccine in adults 50-59 years of age, including adults at increased risk of respiratory syncytial virus lower respiratory tract disease, compared to older adults >=60 years of age.

RSV is an RNA virus of which 2 antigenically distinct subtypes exist, referred
to as RSV A and RSV-B. RSV is a highly contagious human pathogen that causes
respiratory tract infections in people of all ages. In temperate climates
throughout the world, RSV predictably causes fall-winter epidemics. In (sub)
tropical regions, viral activity is more endemic, and outbreaks are less
temporally focused.

RSV is one of the important viral pathogens identified in adults with acute
respiratory infections and is increasingly recognized as a cause of serious
illness in high-risk adults, including those with chronic lung and heart
disease. In a prospective cohort study over 4 RSV seasons in healthy elderly
patients (>=65 YOA) and high-risk adults (>=21 YOA) with chronic heart or lung
disease, RSV infection developed annually in 3% to 7% of healthy elderly
patients and in 4% to 10% of high-risk adults. Healthy elderly patients with
RSV infection required fewer visits to the doctor*s office compared to those
with influenza. Utilization of health care services among high-risk adults with
either RSV infection or influenza was similar. RSV infection in the elderly and
high-risk adults has a disease burden similar to that of a non-pandemic
influenza A in a population with a high rate of influenza vaccination.

In different populations of patients with chronic morbidities both the
prevalence and incidence of RSV infections is increased, leading to an increase
in need for medical care and hospitalization in high income countries. A major
US study reported incidence of RSV-related hospitalizations among different
types of high-risk patients of different age groups, in 2 different settings.
Adults with COPD had 3.2-13.4 times higher hospitalization rates than those
without COPD. Adults with asthma had 2.0 - 3.6 times higher estimated
hospitalization rates than those without asthma. Adults with diabetes had 2.4-
11.4 times higher hospitalization rates than those without diabetes. Adults
with CAD had estimated RSV hospitalization rates 3.7-7.0 times higher than
those without CAD. Estimated IRRs for CHF were the largest; adults with CHF had
4.0 33.2 times higher hospitalization rates than those without CHF. Estimated
IRRs for CHF were highest in the youngest age group and declined with
increasing age. Different European, Asian and US studies have reported an
exacerbation of either COPD, asthma, interstitial pulmonary fibrosis or cystic
fibrosis ranging from 2.2% to 17%. Patients with chronic renal disease as well
as those with chronic liver disease have impaired immune functions due to their
disease pathogenesis, which is associated, in general, with increased
susceptibility to infections.

Primary objective:
To demonstrate the non-inferiority (NI) of the humoral immune response in
healthy participants 50-59 YOA compared to OA (>=60 YOA) for the RSV-A strain
after RSVPreF3 OA investigational vaccine administration.
To demonstrate the NI of the humoral immune response in healthy participants
50-59 YOA compared to OA (>=60 YOA) for the RSV-B strain after RSVPreF3 OA
investigational vaccine administration.
To demonstrate the NI of the humoral immune response in participants 50-59 YOA
at increased risk of RSV-LRTD compared to OA (>=60 YOA) for the RSV-A strain
after RSVPreF3 OA investigational vaccine administration.
To demonstrate the NI of the humoral immune response in participants 50-59 YOA
at increased risk of RSV-LRTD compared to OA (>=60 YOA) for the RSV-B strain
after RSVPreF3 OA investigational vaccine administration.
To evaluate the safety and reactogenicity after the RSVPreF3 OA investigational
vaccine administration.

Secondary Objectives:
To evaluate the humoral immune response to the RSVPreF3 OA investigational
vaccine until 12 months post-study intervention administration.

(Sub study, not in the Netherlands)
To evaluate the CMI response after RSVPreF3 OA investigational vaccine
administration until 12 months post-study intervention administration.

Tertiary
(Tertiary objectives, endpoints, and estimands are optional and might be
assessed only if needed; therefore, not all testing might be performed and
reported)
To evaluate the humoral immune response to the RSVPreF3 OA investigational
vaccine in participants 50-59 YOA at increased risk of RSV LRTD, by baseline
co-morbidities.
To further characterize immune responses to the RSVPreF3 OA investigational
vaccine

Overall Design:
Experimental design: Phase 3, observer/participant-blind, randomized,
placebo-controlled study with 2 cohorts:

Cohort 1 (adults 50-59 YOA) n=1140, with 2 sub-cohorts (Adults-HA (Healthy
Adults) and Adults AIR (at increased risk)) and 4 parallel groups:
o Adults-HA-RSV Group n=380
o Adults-HA-Placebo Group n=190
o Adults-AIR-RSV Group n=380
o Adults-AIR-Placebo Group n=190

Cohort 2 (adults >=60 YOA) with a single group (OA-RSV Group) n=380

Duration of the study: approximately 12 months for all participants.
Primary completion date: Day 31 (1 month after the administration of study
intervention).
Control: placebo saline solution.

Vaccination schedule: Participants will receive a single dose of study
intervention (either RSVPreF3 OA investigational vaccine or placebo) at Visit 1
(Day 1).

Participants will receive a single dose of study intervention (either RSVPreF3
OA investigational vaccine or placebo) at Visit 1.
Study participants must be observed closely for at least 30 minutes after the
administration of the study intervention(s). Appropriate medical treatment must
be readily available during the observation period in case of anaphylaxis,
syncope.

Severe allergic reaction (including itchy skin rash, swelling of the face,
difficulty in breathing and swallowing, or a sudden drop in blood pressure)
have been rarely reported after vaccination.
Syncope (fainting) can occur after or even before any vaccination as a stress
response to the needle injection

Observed 1 op 10:
Pain at injection site
Redness at injection site
Swelling at injection site

People who have received vaccines that contain an adjuvant have very rarely (up
to 1 in 10 000 people) developed autoimmune diseases, which can sometimes be
serious and lifelong.

Procedures:
When giving blood the subject may feel dizzy, faint or experience mild pain,
bruising, irritation, or redness from the needle.