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Centers for Disease Control and Prevention
National Center for Immunization and Respiratory Di seases
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ACIP Adult RSV Work Group Considerations
Respiratory Syncytial Virus (RSV) in Adults Use of RSV vaccines in adults aged 50–59 years
Amadea Britton, MD, MS Advisory Committee on Immunization Practices October 25, 2023
Review current recommendation for use of RSV vaccin es in adults aged 60 years and
older
Summarize available safety and immunogenicity data on the use of RSVPreF3 vaccine
in adults aged 50–59 years
Share preliminary Adult RSV Work Group interpretati ons on the use of RSV vaccines in
adults aged 50–59 years and upcoming policy decisio ns Overview
2
Review of current ACIP recommendation for use of RSV vaccines in adults aged 60 years and older
RSVPreF3 ( Arexvy, GSK ) is a 1-dose adjuvanted (AS01 E) recombinant
prefusion F protein (preF) vaccine.
RSVpreF ( Abrysvo, Pfizer ) is a 1-dose recombinant preF vaccine.* In June 2023, ACIP and CDC recommended the first two RSV
vaccines for older adults.
*The same vaccine formulation is FDA-approved and C DC-recommended for vaccination of pregnant persons for RSV prevention in infants.
https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm4
GSK’s adjuvanted RSVPreF3 and Pfizer’s RSVpreF vaccin es both
demonstrated significant efficacy against lower respiratory tract disease
caused by RSV among older adults over at least two seas ons.
–Trials were underpowered to show efficacy in the olde st adults and in frail adults
–Trials were underpowered to show efficacy against RSV hospitalization, although efficacy
against symptomatic illness may indicate efficacy aga inst more severe disease
Acknowledging these limitations, the Work Group and ACI P felt that RSV
vaccination had the potential to prevent considerable mor bidity from RSV
disease among older adults. Vaccine Efficacy
https://www.cdc.gov/vaccines/acip/meetings/download s/slides-2023-06-21-23/06-RSV-Adults-Melgar-508.pdf5
Six cases of inflammatory neurologic events (includin g Guillain-Barré
syndrome) were reported across trials in older adults within 6 weeks after
RSV vaccination, compared with no cases within 6 weeks after placebo.
–3 cases after vaccination with GSK’s RSVPreF3*
–3 cases after vaccination with Pfizer’s RSVpreF
Imbalance in the small number of atrial fibrillation e vents; more cases
among vaccine recipients, compared with placebo recip ients.
It is unknown at this time whether these events occurred b y chance, or
whether RSV vaccination increases the risk of these eve nts. Vaccine Safety
https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm
* Two of the 3 reported inflammatory neurologic eve nts after vaccination with GSK’s RSVPreF3 were repo rted as acute disseminated encephalomyelitis (ADEM) in
participants that simultaneously received RSVPreF3 vaccine and standard dose seasonal influenza vaccin e. The site investigator that initially reported th e cases has
since revised the diagnosis in both cases (from ADE M to hypoglycemia and dementia, and from ADEM to st roke). FDA’s package insert for RSVPreF3 vaccine continues
to list these as Serious Adverse Events. 6
In June, the Adult RSV Work Group proposed:
–A universal recommendation for RSV vaccination in ad ults 65 and older
–RSV vaccination in adults aged 60–64 years, using s hared clinical decision-making
During ACIP deliberations an amendment was proposed a nd accepted for
the following recommendation:
–Adults ages 60 years and older (both those 60–64 and 65 and older) may receive a single
dose of RSV vaccine using shared clinical-decision maki ng.
The shared clinical decision-making recommendation w as intended to
allow flexibility for providers and patients to conside r individual risk for
RSV disease and target RSV vaccination to those most like ly to benefit. ACIP deliberations leading to a recommendation on t he use
of RSV vaccine in adults 60 and older
ACIP Adult RSV Session. June 21, 2023. Webcast: htt ps://www.youtube.com/watch?v=DunxtgBmRxI&list=PLvrp 9iOIL TQb6D9e1YZWpbUvzfptNMKx2&index=20 7
Chronic underlying medical conditions associated with increased risk of severe RSV disease
Lung disease
Cardiovascular disease
Moderate or severe immune compromise
Diabetes Mellitus
Other conditions that might increase the risk for severe disease Neurologic or neuromuscular conditions
Kidney disorders
Hematologic disorders
Liver disorders
https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm
8
Other factors associated with increased risk of severe RSV disease
Residence in a nursing home or other long-term care facility (L TCF)
Frailty
Advanced age
https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm9
Next steps: new data on the safety and immunogenicity of RSVPreF3 in adults aged 50–59 years
Humoral immune response* at day 31 after a single d ose of RSVPreF3 in adults 60 and
older compared to:
–Adults 50–59, healthy (without prespecified conditions associated with increased risk of severe
RSV disease) OR
–Adults 50–59, at-increased-risk (AIR, with conditions associated with increased risk of severe RSV
disease)
•AIR conditions included: COPD resulting in activity restricting symptoms or use of long-term
medication, chronic cardiovascular disease, diabete s mellitus type 1 or 2, chronic kidney disease,
and chronic liver disease
Cellular immune response appeared similar across gr oups, but was not statistically
evaluated
Safety profile of RSVPreF3 in adults 50–59 years si milar to profile in 60 and older Today, GSK shared data demonstrating that the humoral i mmune
response to a single dose of RSVPreF3 in adults 50– 59 years is non-
inferior to that in adults 60 and older.
*The primary immunogenicity analysis of non-inferio rity of the healthy and at-increased risk (AIR) 50– 59 year-old group versus the established vaccine ag e group of 60 and older
was based on geometric mean titer ratios and serore sponse rates. Data provided by GSK. 11
12 What do these new data mean for future policy?
The non-inferiority data suggest that RSVPreF3 vacc ine efficacy in
(immunocompetent) adults aged 50–59 years with and without chronic medical
conditions that increase risk of RSV disease will b e similar to efficacy
demonstrated among adults 60 years and older.
The Work Group notes that if FDA licensure is granted for use of RSVPreF3 in
adults aged 50–59 years , then ACIP will likely need to make a policy
recommendation on:
–Whether RSV vaccination should be recommended in th is age group?
–And if so, should the recommendation be the same as in adults aged 60 years and
older, i.e. shared clinical decision-making, or is a different type of recommendation
preferred?
13 Additional work group interpretations of immunogeni city data
in adults aged 50–59 years
Persons with immunocompromising conditions were exc luded from this trial (and
prior trials). This is a group likely to benefit fr om RSV vaccination across the age-
spectrum.
Would have preferred efficacy data in this age grou p, noting that there is no
immunologic correlate of protection against RSV dis ease.
If risk conditions are being prioritized, then thos e under 50 are also at risk and
immuno-bridging (and ideally efficacy) studies in a t-risk adults under 50 would
also provide important information.
Work Group considerations on the use of RSV vaccines in adults aged 50–59 years
RSV disease is a public health problem in adults ag ed 50–59 years. However,
the rate of RSV-associated disease in the general p opulation of adults 50–59
years is less than the rate in adults 60 and older.
Adjusted RSV-associated hospitalization rates* per 100,000 adults ≥18 years by 5-year age group and yea r,
RSV-NET, 2015–2016 to 2019–2020
0100 200 300 400 500 600
18–49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 ≥85 Annual RSV-associated hospitalizations
per 100,000 population 2015–16 2016–17 2017–18 2018–19 2019–20
RSV vaccination currently recommended, with SCDM
26–59
23–42
*Unpublished data from RSV-NET. Rates are adjusted for the frequency of RSV testing during recent prio r seasons and the sensitivity of RSV diagnostic tes ts. 15
Persons with certain risk conditions are at increased risk of
severe RSV disease, even at younger ages.
*Clinical data were collected for all patients with laboratory -confirmed RSV hospitalizations during the 2014–2015 to 2 017–2018 seasons, and for an age- and site-stratified r andom sample of patients with
laboratory-confirmed RSV hospitalizations during the 2022– 2023 season. Displayed percentages were weighted for th e probability of selection.
†National Center for Health Statistics. United States, 202 2. National Health Interview Survey. Generated interactiv ely: Oct 17, 2023 from https://wwwn.cdc.gov/NHISDataQ ueryTool/SHS_adult/index.html Prevalence of certain medical conditions *among non-pregnant adults with RSV-associated hospi talizations (RSV-NET, 2014–2015
to 2017–2018 and 2022–2023) and among the general p opulation (National Center for Health Statistics †, 2022) by age group
16 50–64 years ≥65 years
General
population RSV-NET RSV-
NET/
Pop General
population RSV-NET RSV-
NET/
Pop Condition % (95% CI) % (95% CI) % (95% CI) % (95% CI)
Coronary artery disease 5.0 (4.4, 5.6) 18.9 (16.9, 21.0) 3.8 15.3 (14.4, 16.2) 31.3 (29.1, 33.6) 2.0
COPD 6.2 (5.5, 6.9) 35.4 (32.9, 37.9) 5.7 9.8 (9.1, 10.5) 33.2 (30.1, 35.5) 3.4
Diabetes mellitus 13.8 (12.9, 14.7) 37.7 (35.1, 40.4) 2.7 20.1 (19.1, 21.1) 31.8 (29.6, 34.1) 1.6
Asthma 9.1 (8.4, 9.9) 28.6 (26.3, 31.0) 3.1 8.0 (7.3, 8.6) 17.6 (15.8, 19.4) 2.2
Obesity 37.6 (36.2, 38.9) 46.4 (43.7, 49.0) 1.2 30.4 (29.2, 31.6) 28.4 (26.1, 30.8) 0.9
In adults aged 50–59 years, hospitalization rates are higher among Black and
American Indian/Alaska Native adults than among White adults. There is an important equity component when considering the
use of RSV vaccine among adults aged 50–59 years.
*Unpublished data from RSV-NET. Rates are adjusted for the frequency of RSV testing during recent prio r seasons and the sensitivity of RSV diagnostic tes ts. Black, White,
American Indian/Alaska Native and Asian/Pacific Isl ander people were categorized as non-Hispanic 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5
18–49 50–59 60–64 65–74 ≥75
Asian or Pacific Islander White
Hispanic Black
American Indian or Alaska Native Burden-adjusted hospitalization rate ratios* among adults ≥18 years by
race and ethnicity — RSV-NET, 2016–2017 to 2019–2020
17
Work Group is considering multiple policy options.
Upcoming data on the implementation of shared clinica l decision-
making, safety, and effectiveness (if available) wi ll be important to
determine future preferred policy options, both among a dults 50–59 years
and among those 60 and older.
The Work Group continues to believe that a focus on thos e at highest risk
of severe RSV disease is warranted while awaiting pos t-marketing
surveillance data. Work Group preliminary considerations on the policy q uestion
(part 1)
18
19 Work Group preliminary considerations on the policy q uestion
(part 2)
Work Group members broadly agree that use of RSV va ccine among certain adults
aged 50–59 years is likely to have public health be nefit.
–Members particularly acknowledge the equity concern of a recommendation for this
age group.
In addition, they note that if FDA licenses this pr oduct for adults 50–59 years, but
there is NO recommendation made, insurance will not cover use in this age group,
potentially furthering existing disparities.
The current priority of the Work Group is to ensure access to vaccination among
adults 50–59 (and those ≥60) who are at substantial ly increased risk of severe
RSV disease and likely to benefit most.
Risk-based Risk-based Risk-based Risk-based Shared clinical
decision-making Shared clinical
decision-making Shared clinical
decision-making
Universal Universal
50 55 60 65 70 75 80 85 90 Example 5 Example 4 Example 3 Example 2 Example 1 Current recommendation
Age (years) Example potential policy options
20
21 Next steps for the Work Group
Over the next few months, the Work Group will review post-
marketing data on the use of RSV vaccines in adults 60 and older as
they become available, including:
–Vaccine uptake , stratified by demographic characteristics and ris k conditions
–Vaccine safety surveillance
The Work Group will consider the implementation and im plications of
shared clinical decision-making
22 Next steps for the Work Group
The Work Group will then develop an updated policy qu estion for RSV
vaccination in adults through review of:
–Updated GRADE of evidence profile for use of GSK’s RSVPreF3 in adults
–Updated cost effectiveness analysis (CEA) of use of RSVPreF3 in adults
–Updated Evidence to Recommendations framework for adult RSV
vaccination
The Work Group will also begin reviewing safety and efficacy of a new
RSV vaccine (Moderna’s mRNA-1345) for use in adults 60 and older
1. What additional data are needed prior to ACIP votin g on updated recommendations
for RSV vaccination in adults aged ≥50 years?
2. Other questions from ACIP? Questions for ACIP
23
Adult RSV Work Group Membership
24 ACIP Voting Members
Camille Kotton (Chair) Keipp Talbot Sarah Long Ex Officio Members
Rachel Zhang (FDA) Judy Beeler (FDA) Nicholas Geagan (FDA) Nadine Peart Akindele (FDA) Sonnie Kim (NIH/NIAID) Jeffrey Kelman (CMS) Michelle Juaneza (HRSA/VICP) Uzo Chukwuma (IHS) Valerie Marshal (OIDP) Consultants
Robert Atmar (Baylor Coll. of Medicine) Helen Chu (U Washington) Peter Donofrio (Vanderbilt University) Marie Griffin (Vanderbilt University) Cynthia Lucero-Obusan (VHA) Tracy Ruckwardt (NIH/NIAID) Jonathan Temte (U Wisconsin) Rebecca Morgan (Case Western) Doug Campos-Outcalt (U Arizona)
Liaisons
Kenneth Schmader (AGS) Vidya Sundareshan (ACP) Gretchen LaSalle (AAFP) April Killikelly (NACI/PHAC) Winnie Su (NACI/PHAC) Katherine Williams (APTR) Ruth Lynfield (NFID) Bindy Crouch (AIM) Steven Pergam (IDSA) Elizabeth Skoy (APhA)
CDC Contributors
Michael Melgar (co-lead) Lauren Roper Fiona Havers Elisha Hall Chris Taylor Monica Patton Meredith McMorrow Diya Surie Jennifer DeCuir Mila Prill Monica Godfrey Ruth Link-Gelles Amanda Payne Danielle Moulia Megan Wallace Natalie Thornburg Melissa Coughlin Jefferson Jones Katherine Fleming-Dutra Ismael Ortega Sanchez Noelle Molinari Pragna Patel Aron Hall Hannah Rosenblum Derrell Powers Raigan Wheeler Jarrett Gartin Elizabeth Greene Manisha Patel Lisa Grohskopf Anne Hause David Shay Christine Olson Tom Shimabukuro Karen Broder Neil Murthy Patricia Wodi Andrew Leidner Jamison Pike Sarah Meyer Nicole Dowling
25
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The findings and conclusions in this report are tho se of the authors and do not necessarily represent the official
position of the Centers for Disease Control and Pre vention.
Photographs and images included in this presentatio n are licensed solely for CDC/NCIRD online and pres entation
use. No rights are implied or extended for use in p rinting or any use by other CDC CIOs or any externa l audiences.