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© 2024 Moderna, inc. All rights reserved.Overview of Moderna’s 
Investigational RSV Vaccine (mRNA-1345) in Adults ≥ 60 Years of Age
Advisory Committee on Immunization Practices (ACIP)
Rituparna Das, MD, PhD
Feb 29, 2024The safety and efficacy of this investigational RSV vaccine have 
not been established in any country for any use   
Outline of 
PresentationOverview of mRNA- 1345, Moderna’s 
investigational RSV vaccine
Pivotal Phase 2/3 trial
Efficacy
Safety
Immunogenicity
Persistence of antibody and revaccination – 
 Phase 1 trial
Concomitant administration with influenza and 
COVID- 19 vaccines
Summary 
NE-3
Investigational RSV Vaccine (mRNA -1345) Designed to Encode 
for a Stabilized Prefusion F Glycoprotein
•LNP encapsulated mRNA -based vaccine 
encoding the RSV fusion (F) glycoprotein
stabilized in the prefusion conformation
•Prefusion F elicits potent neutralizing 
antibody response1,2
•Antibodies to the F protein cross -react between RSV -A and RSV -B
•RSV vaccine uses the same LNP as 
Moderna COVID -19 vaccines3
•Phase 1: mRNA -1345 is well tolerated with 
persistent antibody levels through 12 
months4
1. Crank et al. Science , 2019;  2. McKekkan et al. Science, 2013; 3. Aranda and Polack, Front Immunol , 2019; 4. Simorellis et al. ESWI  2023 
NE-4
Pivotal Safety and Efficacy Trial of RSV Vaccine, 
mRNA-1345 (Study 301)
NE-5
Study Design
Population
Healthy adults including those with chronic, stable medical conditions, and/or frailty 
≥ 60 years of age
22 countries (both Northern and Southern Hemisphere)
Regimen and follow -up
Single-dose regimen (1:1 50 μg RSV vaccine or saline placebo)
24-month follow -up
Weekly active RSV case surveillance performed throughout study to addresses 
unpredictability of RSV seasons following pandemic
Stratified by 
Age (60 - 74 and ≥ 75 years)
Presence or absence of congestive heart failure or chronic  obstructive pulmonary 
diseaseStudy 301
clinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434
NE-6
Enrollment Enriched for High -Risk Groups
Study 301
COPD
CHF
Asthma
Chronic respiratory disease1 
Diabetes
Advanced liver disease
Advanced renal diseaseMeasured by Edmonton Frail Scale across 9 domains: 
Cognition
General health status
Functional independence
Social support
Medication use
0-17 point scale
Fit (0 –3)
Vulnerable (4– 5)
Frail (6 -17)
Individuals with Comorbidities
 Frail Individuals
1 Chronic respiratory disease includes chronic pulmonary 
fibrosis (idiopathic and otherwise), restrictive lung 
disease, asbestosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, and history of tuberculosisNutrition
Mood
Continence
Functional 
performance
NE-7
Study Design – Randomization
Study 301
No safety signals identified after DSMB review of Phase 2 safety data
Allowed for seamless transition to start of Phase 3Adults 
≥ 60 Years
N = 36,557 
Clinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434
DSMB = Data Safety and Monitoring Board
Phase 2
United States
Initiated November 2021
N = 1,991
Phase 3
Global Sites
Initiated February 2022
N = 34,566
Investigational RSV Vaccine (mRNA -1345, 50 μg)
N = 993
Placebo
N = 998
Investigational RSV Vaccine (mRNA -1345, 50 μg)
N = 17,311
Placebo
N = 17,2551:1
1:1
NE-8
36,557 Participants Enrolled in 22 Countries 
(as of April 30, 2023 data cutoff)
Study 301
Number of participants in each country shown in parentheses269 Study Sites Across Northern and Southern Hemisphere
Australia  (256) 
Bangladesh (2,421)
Japan  (822) 
New Zealand  (299)
Singapore  (8) 
South Korea (27)
Taiwan  (84)
South Africa (982)Belgium  (413)
Finland (96)
Germany  (471)
Poland (346)
Spain (220)
United Kingdom (450) Canada  (706)
United States  (19,571)
Mexico  (733)
Argentina  (3,589)
Chile  (679)
Colombia  (2,625)
Costa Rica (208)
Panama  (1,551)Randomization Set
NE-9
Primary and Additional Efficacy Analyses
US 2021-2023 RSV Hospitalization Rates (RSV -NET) in Adults ≥ 65 Years1
*Median RSV hospitalization rate for 2016 – 2019. Data only collected from October to April each year. 
1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://data.cdc.gov/Public -Health- Surveilla nce/Weekly -Rates -of-Laboratory -Confirmed -RSV-Hospitali/29hc -
w46k/data_preview. 2. Wilson E, et al. NEJM. 2023;389:2233- 2244. RSV efficacy study 
conducted across2021 – 2022 and 
2022 – 2023 seasons
>50% of participants enrolled in US
Primary Analysis: Met success criteria
2
Additional Analysis: 94% of participants followed for ≥ 6 monthsOverall RSV 
Hospitalization 
Rate per 
100,000 Adults 
≥ 65 Years 
01234567
2016 -2019 
RSV Seasons*2021 -2022 
RSV Season 2016 -2019 
RSV Seasons*Additional  Analysis
November 2021 –  April 2023
Median 8.6 Months (range 0.5 – 17.7) Follow -upVaccination Period
November 2021 –  December 2022
Primary Analysis
November 2021 –  November 2022
Median 3.7 Months (range 0.5 - 12.6) Follow -up
2022 -2023 
RSV Season
NE-10
Demographics of Study Participants
CharacteristicRSV Vaccine (mRNA -1345)
(N = 18,304)Placebo
(N = 18,253)
Median Age, years 67 67
Male, n (%) 9,376 ( 51%) 9,277 (51%)
Age Group, n (%)
60 – 69 Years 11,348 (62%) 11,301 (62%)
70 – 79 Years 5,512 (30%) 5,500 (30%)
≥ 80 Years 1,444 (8%) 1,452 (8%)
Race/Ethnicity, n (%)
White 11,318 (62%) 11,290 (62%)
Black or African American 2,210 (12%) 2,175 (12%)
Asian 2,014 (11%) 2,001 (11%)
American Indian or Alaska Native 907 (5%) 897 (5%)
Native Hawaiian or Other Pacific Islander 28 (0.2%) 19 (0.1%)
Hispanic / Latino Ethnicity 6,118 (33%) 6,169 (34%)Study 301
Age, gender, race, and ethnicity balanced between vaccine and placebo recipients
Race/ethnicity generally representative of US populationRandomization Set
NE-11
1. Chronic respiratory disease includes chronic pulmonary fibrosis (idiopathic and otherwise), restrictive lung disease, asbesto sis, bronchiectasis, cystic fibrosis,
    pulmonary hypertension, sarcoidosis, and history of tuberculosis 
2. Based on 17- point Edmonton Frailty ScoreParticipants with Lower Respiratory Tract Disease (LRTD) 
Risk Factors and Comorbidities of Interest 
CharacteristicRSV Vaccine (mRNA -1345)
(N = 18,304)Placebo
(N =18,253)
CHF or COPD, n (%) 1,310 (7%) 1,316 (7%)
≥1 Comorbidity of Interest, n (%)
COPD, CHF, asthma, chronic respiratory disease1, 
diabetes, advanced liver disease, advanced renal disease5,417 (30%) 5,316 (29%)
Frailty2, n (%)
Vulnerable (score of 4- 5) 2,852 (16%) 2,917 (16%)
Frail (score of 6- 17) 1,013 (6%) 1,033 (6%)Study 301
Randomization Set
Enrollment included those at highest risk of severe RSV
NE-12
Safety Data
Study 301
Safety Set –  April 30, 2023 data cutoff
Based on 6 months of follow -up for ~94% of participants
NE-13
Primary Safety Endpoints and Duration of Follow -up
Study 301
1. Neurologic events of interest include Guillain -Barre syndrome, 
acute disseminated encephalomyelitis, Bell’s palsy, and seizuresActive Safety 
SurveillanceSolicited Local and 
Systemic Adverse 
Reactions
Unsolicited Adverse Events
Medically Attended AEs, Serious AEs Including Death, AEs Leading to 
Discontinuations
Adverse Events of Special Interest(including Myocarditis, Pericarditis, Thrombocytopenia, Neurologic Events
1, and Anaphylaxis )
7 Days 28 Days 24 months
(ongoing)
NE-14Solicited Local Reactions within 7 Days After RSV Vaccine vs 
Placebo
Study 301 - Solicited Safety Set 
55.9%
13.8%
2.0% 0.6%3.7%0.0%15.2%
6.1%
0%20%40%60%80%100%Injection 
Site PainInjection Site 
ErythemaInjection Site 
SwellingAxillary Swelling 
or Tenderness
<1%Grade 2
Grade 3Grade 1
RSV vaccine, n=18174; placebo, n=18102
For placebo, grade 2 erythema and grade 2 and grade 3 swelling were < 1%No grade 4 local adverse reactionsSafety Set
Mostly grade 1, onset day 1-2, median duration of 1 -2 days for RSV vaccinePlacebo RSV Placebo RSV Placebo RSV Placebo RSV
NE-15Solicited Systemic Reactions within 7 Days After RSV Vaccine vs 
Placebo
Study 301 - Solicited Safety Set 
2.8% 1.3%26.7%
18.8%30.8%
20.0%25.6%
14.4%21.7%
14.0%
7.0%5.3%11.6%
6.8%
0%20%40%60%80%100%Headache Fatigue Myalgia ArthralgiaNausea / 
VomitingChills Fever
RSV vaccine, n=18174; placebo, n=18102
Grade 4 fever was reported (mRNA -1345 [n=29] and placebo [n=35]); no other categories reported any grade 4 reactionsSafety Set
Mostly grade 1, onset day 1-2, median duration of 1 -2 days for RSV vaccineGrade 2
Grade 3Grade 1
Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV 
NE-16Unsolicited Adverse Events Within 28 Days After Injection, 
Regardless of Relationship to Vaccine/Placebo
RSV Vaccine (mRNA -1345)
(N = 18,245)Placebo
(N = 18,184)
 All, n (%) 3,749 (21%) 3,412 (19%)
Serious 115 (0.6%) 111(0.6%)
Fatal 1(<0.1%) 6 (<0.1%)
Medically -Attended 1,606 (9%) 1,531 (8%)
Leading to Study Discontinuation 2(<0.1%) 11(<0.1%)
Severe/≥ Grade 3 129(0.7%) 135(0.7%)
Non- Serious 3,634 (20%) 3,301 (18%)
Any Adverse Event of Special Interest  (AESI) 3(<0.1%) 8(<0.1%)Study 301 - Solicited Safety Set 
No imbalances in any categories between vaccine and placebo recipientsSafety Set
Based on April 30, 2023 cutoff
NE-17
Adverse Events of Special Interest (AESI)
Neurological Disorders
No cases of Guillain- Barre syndrome or acute disseminated 
encephalomyelitis (ADEM) 
No imbalance observed for other neurological disorders including Bell’s 
palsy/facial paralysis
Cardiac Events
No imbalance observed in cardiac arrhythmias such as atrial fibrillation
No CEAC adjudicated cases of:
Acute myocarditis in vaccine recipients
Acute pericarditis in vaccine recipients with onset < 42 daysStudy 301 
Safety Set
CEAC – Cardiac Event Adjudication Committee
 Based on April 30, 2023 cutoff
NE-18
Efficacy
Study 301
NE-19
Key Efficacy Endpoints 
Study 301
Vaccine efficacy to prevent first episode of RSV -LRTD (Lower Respiratory Tract Disease) 
between 14 days and 12 months post -injection
≥ 2 signs/symptoms
≥ 3 signs /symptoms
Primary Efficacy Objectives
Vaccine efficacy to prevent:
First episode of RSV -ARD (Acute Respiratory Disease) between 14 days and 12 months post -
injection
First hospitalization associated with RSV -ARD or RSV -LRTD between 14 days and 12 months 
post-injection
Key Secondary Efficacy Objectives
Vaccine efficacy against RSV -LRTD with shortness of breath (a surrogate measure of more severe 
disease)1, 2
Exploratory Endpoint
1. Falsey et al NEJM , 2005; 2. Panozzo et al ESWI , 2023  
NE-20
Definitions of LRTD and ARD
Study 301
+
RT-PCR
Confirmed
 RSVRSV Lower Respiratory Tract Disease (LRTD)
New or Worsening of ≥ 2 or ≥ 3 of Signs/Symptoms for ≥ 24 Hours
RSV Acute Respiratory Disease (ARD) 
New or Worsening of ≥ 1 Signs/Symptoms for ≥ 24 Hours
Sinus 
PainHoarsenessStuffy 
NoseTachypneaShortness 
of BreathSputum 
Production
Wheezing
Sore 
ThroatRunny 
NoseChills HypoxemiaFeverPleuritic 
Chest PainCoughTachypneaShortness 
of BreathSputum 
Production Wheezing 
and/or 
rales and/or 
rhonchiFever and/ 
or CoughHypoxemiaPleuritic 
Chest Pain
LRTD cases are a subset of the ARD cases 
RSV surveillance was conducted year-round throughout study follow-up
NE-21
Primary Analysis
Study 301
Per Protocol Analysis – November 30, 2022 data cutoff
NE-22Efficacy of mRNA -1345 Against RSV LRTD and RSV ARD 
among Adults ≥ 60 Years
Study 301  - Per Protocol Analysis
Vaccine efficacy for primary and key secondary endpoints (median 3.7 months) met lower bound 
of CI criterion (>20%)
Regulatory criteria for licensure metPrimary Analysis
1. Alpha adjusted CI: 95.88% for RSV LRTD ≥ 2 symptoms, 96.36% for RSV LRTD ≥ 3 symptoms, 95.0% for RSV ARD
Wilson et al. NEJM,  2023Cases, n (%)
RSV Vaccine 
(mRNA- 1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy (%) 
Based on Hazard Ratios1
RSV LRTD
≥ 2 symptoms9 (0.05%) 55 (0.31%)83.7%
(66.0%, 92.2%)
RSV LRTD
≥ 3 symptoms3 (0.02%) 17 (0.10%)82.4% 
(34.8%, 95.3%)
RSV ARD 26 (0.15%) 82 (0.47%)68.4%
(50.9%, 79.7%)
NE-23
Vaccine Efficacy Against RSV -A and RSV-B by Endpoint 
Numbers of Events
RSV Vaccine 
(mRNA -1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy
(CI)
RSV LRTD
≥ 2 Symptoms Overall 9 55 83.7% (66.0, 92.2)
RSV-A 3 36 91.7% (73.0, 97.4)
RSV-B 6 19 68.5% (21.1, 87.4)
RSV LRTD≥ 3 Symptoms Overall 3 17 82.4% (34.8, 95.3)
RSV-A 1 10 90.0% (22.0, 98.7)
RSV-B 2 7 71.5% (-37.0, 94.1)
RSV-ARDOverall 26 82 68.4% (50.9, 79.7)
RSV-A 11 51 78.5% (58.8, 88.8)
RSV-B 15 31 51.7% (10.6, 73.9)Study 301 -  Per-Protocol Efficacy Set
-40 -20 0 20 40 60 80 100Primary Analysis
Efficacy was observed for both RSV -A and RSV -B
Fewer cases of LRTD ≥ 3 symptoms resulted in larger confidence intervals for both subtypesVaccine Efficacy, % (Adjusted CIs)
Wilson et al. NEJM , 2023
NE-24Vaccine Efficacy by Age, Comorbidities, and Frailty 
Against RSV LRTD ≥ 2 Symptoms  
Numbers of Events
RSV LRTD with ≥ 2 Symptoms RSV Vaccine 
(mRNA -1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy
(CI)
Overall 9 / 17,572 55 / 17,516 83.7% (66.0, 92.2)
Age60 – 69 Years 8 / 11,168 33 / 11,118 76.0% (48.0, 88.9)
70 – 79 Years 1 / 5,440 22 / 5,416 95.4% (65.9, 99.4)
≥ 80 Years 0 / 964 0 / 982 –
ComorbiditiesNo Comorbidities 7 / 12,377 38 / 12,431 81.6% (58.8, 91.8)
≥ 1 Comorbidities 2 / 5,195 17 / 5,085 88.4% (49.9, 97.3)
Frailty StatusFit (0-3) 8 / 13,396 45 / 13,250 82.3% (62.5, 91.7)
Vulnerable/Frail (≥ 4) 0 / 3,781 6 / 3,858 100.0% (NE, 100.0)Study 301 - Per-Protocol Efficacy Set
-40 -20 0 20 40 60 80 100Primary Analysis
Vaccine Efficacy, % (Adjusted CIs)
Case splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty
No cases observed in ≥ 80- year-olds 
Wilson et al. NEJM, 2023; NE - nonestimable
Comorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal disease
NE-25
Cases, n (%)
RSV Vaccine 
(mRNA -1345)
(N = 17,572)Placebo
(N = 17,516)Vaccine Efficacy (%) 
Based on Hazard Ratios 
(95% CI)
RSV-LRTD Associated 
Shortness of Breath1,2 2 (0.01%) 15 (0.09%)86.7% 
(41.9%, 97.0%)
Medically Attended RSV -LRTD 
(≥ 2 Symptoms and ER/Urgent Care)0 5 (0.03%) NEEfficacy Against Severe (based on Shortness of Breath) 
and Medically Attended LRTD Among Adults ≥ 60 Years
Study 301 - Post Hoc Analysis/Per Protocol Analysis
Post Hoc Analysis
Shortness of breath is a key driver of seeking a higher level of care1,2 
Vaccine is efficacious in preventing shortness of breath associated with RSV -LRTD
Case split favorable for medically attended RSV -LRTD (ER/urgent care visits)
Based on Nov 30, 2022 cutoff; NE - nonestimable
1.Falsey et al NEJM, 2005; 2. Panozzo et al. ESWI , 2023 
NE-26
Additional Analysis
Study 301
Per Protocol Analysis – April 30, 2023 data cutoff
NE-27Efficacy of mRNA -1345 Against RSV LRTD and RSV ARD 
among Adults ≥ 60 Years
Study 301 - Per Protocol Analysis
Additional Analysis 
Vaccine protection continues over a longer period (median 8.6 months) through high-transmission 2022/2023 
RSV season
Lower bound of the confidence interval continued to exceed 20%Cases, n (%)
RSV Vaccine 
(mRNA- 1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy (%) 
Based on Hazard Ratios 
(95% CI)
RSV LRTD
≥ 2 symptoms47 (0.26%) 127 (0.70%)63.3%
(48.7%, 73.7%)
RSV LRTD
≥ 3 symptoms19 (0.10%) 51 (0.28%)63.0% 
(37.3%, 78.2%)
RSV ARD 86 (0.47%) 185 (1.03%)53.9%
(40.5%, 64.3%)
NE-28Cumulative Incidence Curve – Efficacy Against RSV 
LRTD with ≥ 2 Symptoms among Adults ≥ 60 Years
Study 301 - Per-Protocol Efficacy Set
Data cutoff date: Apr 30, 2023; *based on hazard ratio Additional Analysis 
Cumulative 
Incidence 
Rate
(%)
Time from Randomization (Months)Vaccine Efficacy *
(95% CI)
63.3%
(48.7%, 73.7%)
8.6 months median 
follow -up (range 
0.5-17.7 months)
Separation in curves observed early and  sustained through follow -up 
mRNA -1345 18112 18040 17971 17886 17789 17355 17076 14191 10634 7534 5073 3474 2327
Placebo 18045 17940 17845 17735 17623 17185 16908 14060 10591 7460 5021 3442 23030.01.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0 1 2 3 4 5 6 7 8 9 10 11 12Placebo
RSV Vaccine 
(mRNA -1345)
number at risk
NE-29
Vaccine Efficacy Against RSV -A and RSV-B by Endpoint 
Numbers of Events
RSV Vaccine 
(mRNA -1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy
(CI)
RSV LRTD
≥ 2 Symptoms Overall 47 127 63.3% (48.7, 73.7)
RSV-A 24 78 69.4%  (51.7, 80.6)
RSV-B 22 50 56.3%  (27.9, 73.5)
RSV LRTD
≥ 3 Symptoms Overall 19 51 63.0% (37.3, 78.2)
RSV-A 10 30 66.9%  (32.2, 83.8)
RSV-B 9 22 59.3%  (11.7, 81.3)
RSV-ARDOverall 86 185 53.9% (40.5, 64.3)
RSV-A 43 106 59.7%  (42.5, 71.7)
RSV-B 42 80 47.9%  (24.3, 64.1)Study 301 - Per-Protocol Efficacy Set
-40 -20 0 20 40 60 80 100
Vaccine Efficacy, % (Adjusted CIs)Additional Analysis 
Efficacy was observed for both RSV -A and RSV -B
NE-30Vaccine Efficacy by Age, Comorbidities, and Frailty 
Against RSV LRTD ≥ 2 Symptoms  
Study 301 - Per-Protocol Efficacy Set
Case splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty
Too few cases in ≥ 80- year-olds to assess efficacy Numbers of Events
RSV LRTD with ≥ 2 Symptoms RSV Vaccine 
(mRNA -1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy
(CI)
Overall 47/18,112 127/18,045 63.3% (48.7, 73.7)
Age60 – 69 Years 31/11,219 77/11,170 60.1%  (39.5, 73.7)
70 – 79 Years 10/5,464 45/5,439 78.0%  (56.3, 88.9)
≥ 80 Years 6/1,429 5/1,436 NE
ComorbiditiesNo Comorbidities 31/12,751 76/12,796 59.5%  (38.5, 73.4)
≥ 1 Comorbidities 16/5,361 51/5,249 69.3%  (46.1, 82.5)
Frailty StatusFit (0-3) 37/13,417 104/13,274 65.0%  (49.0, 75.9)
Vulnerable/Frail (≥ 4) 9/3,817 17/3,884 46.5%  (-20.0, 76.2)
-40 -20 0 20 40 60 80 100
Vaccine Efficacy, % (95% CIs)Additional Analysis 
NE - nonestimable
Comorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal disease
NE-31Efficacy Against Severe LRTD and Hospitalizations 
Among Adults ≥ 60 Years
Cases, n (%)
RSV Vaccine (mRNA -
1345)
(N = 18,112)Placebo
(N = 18,045)Vaccine Efficacy  (%) 
Based on Hazard Ratios
(95% CI)
RSV-LRTD Associated Shortness of 
Breath1,211 (0.06%) 43 (0.24%)74.6%
(50.7%, 86.9%)
RSV LRTD with ≥ 2 Symptoms and 
ER/Urgent Care5 (0.03%) 13 (0.07%)61.8%
(-7.35, 86.45)
Hospitalizations 0 (0%) 2 (0.01%) NEStudy 301 - Post Hoc Analysis/Per Protocol Analysis
Based on April 30, 2023 cutoff
NE -  nonestimable
1. Falsey  et al NEJM , 2005; 2. Panozzo et al ESWI , 2023  Shortness of breath is a key driver of seeking a higher level of care1,2 
Vaccine is efficacious in preventing:
Shortness of breath associated with RSV -LRTD
Medically attended RSV -LRTD (ER/urgent care visits)
2 hospitalizations in placebo recipients (both >70 years with comorbid conditions [asthma]; both recovered)Additional Analysis 
NE-32
Immunogenicity
Study 301
Immunogenicity Subset
NE-33
RSV-A 
Assay
RSV-B 
AssayNeutralizing Antibody Response by RSV Subtype – 
Baseline and Day 29
Study 301 - Microneutralization Antibody (IU/mL)
1350 1305 14257246
1001,00010,000100,000
All Participants Baseline Day 29 Baseline Day 29
5.1-fold rise
(N = 333) (N = 1515)mRNA -1345 
(50 µg)
Placebo
Participants had 
baseline titers consistent with prior exposure to 
RSV
One dose of 50 μg of 
mRNA -1345 increased 
titers by:
>8-fold for RSV -A
>5-fold for RSV -B2404 2417 255321475
1001,00010,000100,000
All Participants Baseline Day 29 Baseline Day 29
8.4-fold rise
GMT
IU/mL
(95% CI)
(N = 333) (N = 1515)Per Protocol Immunogenicity Set
GMT
IU/mL
(95% CI)
NE-34
RSV-B 
AssayRSV-A 
AssayNeutralizing Antibody Response by RSV Subtype and Age – 
Baseline and Day 29 
Study 301 – Microneutralization Antibody (IU/mL)
Per Protocol Immunogenicity Set
Baseline titers similar across age groups
Day 29 titers and fold rise are similar across age groups60–69 Years 70–79 Years  ≥ 80 Years  
230922612
274720374
270621812
1001,00010,000100,000
Baseline Day 29 Baseline Day 29 Baseline Day 29
GMT
IU/mL
(95% CI)GMT
IU/mL
(95% CI)
9.8-fold rise
 7.5-fold rise
 8.1-fold rise
5.5-fold rise
 4.8-fold rise
 5.1-fold risemRNA -1345 (50 µg)
13537457
14987093
14167139
1001,00010,000100,000
Baseline Day 29 Baseline Day 29 Baseline Day 29(n = 619) (n = 618) (n = 671) (n = 671) (n = 223) (n = 222)
(n = 617) (n = 616) (n = 672) (n = 671) (n = 223) (n = 222)Age by Decade
NE-35
T-cell Responses Following Receipt of mRNA -1345
CRID- 001 Study - 15 Adults, 50- 75 Years Old
CD4+ T cells CD8+ T cells
•Vaccine elicits persistent CD4+ and CD8+ T -cell responses RSV- F antigen specific, Interferon -γ+ T-cells (intracellular cytokine staining assay)
NE-36Durability of RSV -A and RSV -B Neutralizing Antibody Response with 
mRNA- 1345 and Revaccination 
Study 101 – Adults 65- 79 Years 
100100010000100000
0123 6 121314RSV-A Neutralizing Antibody
100100010000100000
0123 6 121314
RSV-B Neutralizing Antibody
GMT 
(95% CI)
Study Month
Study Month•RSV-A and RSV -B neutralizing antibodies detectable at 12 months post- vaccination, 2-3 fold above baseline
•Revaccination at 12 months results in increase in GMT  
•Revaccination at 1 and 2 years is being evaluated in Phase 3 studiesGMFR from Day 0 10.1 6.96.8 5.5 2.77.37.0
Study Month6.46.85.8 4.5 2.55.24.5
N = 14 -18 adults
Simorellis et al, ESWI  2023
NE-37
Concomitant Administration of RSV Vaccine 
(mRNA1345) with Quadrivalent Influenza Vaccine (Afluria) or Bivalent COVID -19 Vaccine 
(mRNA-1273.214)
Study 302, Parts A & B
NE-38
Study 302: Safety and Immunogenicity Study of Concomitant Administration 
of mRNA- 1345 with Quadrivalent Influenza Vaccine (Afluria) or COVID -19 
Bivalent Vaccine in Adults ≥ 50
Planned 
Sample Size Randomized
RSV Vaccine PlaceboCOVID- 19 
Bivalent Vaccine
RSV VaccineCOVID- 19 
Bivalent VaccinePlacebo
COVID- 19 
Bivalent VaccinePlacebo PlaceboPart B
Group 1
Group 2
Group 3RSV Vaccine Placebo
RSV VaccineQuadrivalent 
Flu Vaccine
Quadrivalent 
Flu VaccinePlacebo
Group 1
Group 2
Group 3Part ADay 1
Day 29420 2491
600 690
600 692
560 562
560 566
560 563
1.Due to randomization error, sample size lower than planned
NE-39
Comparison of Day 29 Geometric Mean Titer Ratio (GMR) – Concomitant vs 
Nonconcomitant Administration of mRNA -1345 and Quadrivalent Influenza Vaccine
Antibody GMR (95% CI)
RSV-A Neutralizing Antibody (IU/mL) 0.81 (0.67, 0.97)
RSV-B Neutralizing Antibody (IU/mL) 0.85 (0.73, 1.00)
Influenza A/H1N1 Antibody 0.89 (0.77, 1.03)
Influenza A/H3N2 Antibody 0.97 (0.86, 1.09)
Influenza B/Phuket Antibody 0.91 (0.81, 1.02)
Influenza B/Washington Antibody 0.93 (0.82, 1.05)Study 302, Part A
0.5 1 1.5
All GMR non -inferiority criteria met (LB of the 2- sided 95% CI of GMR > 0.667)GMR  (95% CI)0.667
NE-40
Comparison of Day 29 Geometric Mean Titer Ratio (GMR) – Concomitant vs 
Nonconcomitant Administration of mRNA -1345 and COVID -19 Bivalent Vaccine
Antibody GMR (95% CI)
RSV-A Neutralizing Antibody (IU/mL) 0.80 (0.70, 0.90)
RSV-B Neutralizing Antibody (IU/mL) 0.89 (0.79, 1.00)
COVID- 19 (Wuhan) (AU/ml) 0.96 (0.87, 1.06)
COVID- 19 (Omicron) (AU/ml) 1.01 (0.89, 1.14)Study 302, Part B
0.5 1 1.5
GMR  (95% CI)0.667
All GMR non -inferiority criteria met (LB of the 2- sided 95% CI of GMR > 0.667)
NE-41Solicited Local Reactions within 7 Days After mRNA -1345 Alone or 
Co-administered with Quadrivalent influenza Vaccine (Afluria) in Adults ≥ 50
Study 302, Part A - Solicited Safety Set
mRNA -1345 + Afluria,  n= 678; mRNA -1345 + placebo, n= 249; Afluria + placebo;  n= 683
One grade 4 event (0.4%) of axillary swelling or tenderness in mRNA -1345 + placebo group
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + Flu Solicited Safety Set
48% 47%
26%
1% 1% 2% 2% 3%1%12%15%
9%
0%10%20%30%40%50%60%70%80%90%100%
mRNA
+ flumRNA
+ pboflu +
pbomRNA
+ flumRNA
+ pboflu +
pbomRNA
+ flumRNA
+ pboflu +
pbomRNA
+ flumRNA
+ pboflu +
pboInjection Site Pain Injection Site 
ErythemaInjection Site 
SwellingAxillary Swelling 
or Tenderness
%Grade 1
Grade 2
Grade 3 + 4
RSV + 
AfluriaAfluria + 
PlaceboRSV + 
PlaceboRSV + 
AfluriaAfluria + 
PlaceboRSV + 
PlaceboRSV + 
AfluriaAfluria + 
PlaceboRSV + 
PlaceboRSV + 
AfluriaAfluria + 
PlaceboRSV + 
Placebo
NE-42Solicited Systemic Reactions within 7 Days After mRNA -1345 Alone or 
Co-administered with Quadrivalent Influenza Vaccine in Adults ≥ 50
Study 302, Part A - Solicited Safety Set
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + Flu Solicited Safety Set
20% 21%14%9% 11%7% 9% 11%7%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo3%7%2%23% 25%17%26% 25% 22% 24% 23%
14%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pboFever Headache Fatigue Myalgia
%
Arthralgia Nausea / Vomiting Chills
%Grade 1
Grade 2
Grade 3 + 4
mRNA -1345 + Afluria,  n= 678; mRNA -1345 + placebo, n= 249; Afluria + placebo;  n= 683
Grade 4 fever reported in  1 recipient of mRNA 1345+ placeboRSV + 
AfluriaAfluria + 
PlaceboRSV + 
PlaceboRSV + 
AfluriaAfluria + 
PlaceboRSV + 
PlaceboRSV + 
AfluriaAfluria + 
PlaceboRSV + 
PlaceboRSV + 
AfluriaAfluria + 
PlaceboRSV + 
Placebo
NE-43Solicited Local Reactions within 7 Days After mRNA -1345 Alone or 
Co-administered with COVID -19 Bivalent Vaccine in Adults ≥ 50
Study 302, Part B - Solicited Safety Set
mRNA -1345 + COVID -19, n= 558; mRNA -1345 + placebo, n= 555; COVID -19 + placebo;  n= 557
No grade 4 eventsSolicited Safety Set
61%
54% 55%
3% 3% 3% 3% 3% 3%19%17% 15%
0%10%20%30%40%50%60%70%80%90%100%
rsv +
covidrsv +
pbocovid +
pborsv +
covidrsv +
pbocovid +
pborsv +
covidrsv +
pbocovid +
pborsv +
covidrsv +
pbocovid +
pboInjection Site Pain Injection Site 
ErythemaInjection Site 
SwellingAxillary Swelling 
or Tenderness
%Grade 1
Grade 2
Grade 3
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + COVID -19
RSV + 
COVID-19COVID-19 
+ PlaceboRSV 
+ 
PlaceboRSV + 
COVID-19COVID-19 
+ Placebo RSV 
+ 
PlaceboRSV + 
COVID-19COVID-19 
+ PlaceboRSV 
+ 
PlaceboRSV + 
COVID-19COVID-19 
+ PlaceboRSV 
+ 
Placebo
NE-44Solicited Systemic Reactions within 7 Days After mRNA -1345 Alone or 
Co-administered with COVID -19 Bivalent Vaccine in Adults ≥ 50
Study 302, Part B - Solicited Safety Set
Mostly grade 1, onset day 1-2, median duration of 2 days for RSV + COVID -19 Solicited Safety Set
35%
22%26%
10%7% 9%22%
13%17%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo8%2% 3%32%27% 30%41%
30% 33%40%
27%31%
0%20%40%60%80%100%
mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pbo mRNA +
flumRNA +
pboflu + pboFever Headache Fatigue Myalgia
%
Arthralgia Nausea / Vomiting Chills
%Grade 1
Grade 2
Grade 3 + 4
mRNA -1345 + COVID -19 vaccine,  n= 558; mRNA -1345 + placebo, n= 555; COVID -19 vaccine + placebo;  n= 557
Grade 4 fever reported in 1 recipient of COVID -19 + placeboRSV + 
COVID-19COVID-19 
+ PlaceboRSV 
+ 
PlaceboRSV + 
COVID-19COVID-19 
+ PlaceboRSV 
+ 
PlaceboRSV + 
COVID-19COVID-19 
+ PlaceboRSV 
+ 
PlaceboRSV + 
COVID-19COVID-19 
+ PlaceboRSV 
+ 
Placebo
NE-45Safety Events of Interest – Study of Concomitant Administration of 
mRNA- 1345 with Influenza or COVID -19 Vaccine
No reports of: 
Deaths, SAEs, or AESIs as assessed as related by the investigator
Anaphylaxis
Guillain Barre Syndrome
Acute disseminated encephalomyelitis (ADEM)
Bell’s palsy/facial paralysis
Acute myocarditis or acute pericarditisStudy 302 A and B – Based on 6 Months Follow-up
Safety Set
NE-46
SUMMARY
NE-47
Vaccine efficacious; met all regulatory criteria for licensure
Continued to be efficacious through median 8.6 months follow -up
Shown to prevent severe RSV disease (based on analysis of shortness of breath
 and medically attended RSV -LRTD)Investigational RSV Vaccine (mRNA -1345)
Safety
Efficacy  Vaccine generally well tolerated in >19,500 individuals
No GBS, no ADEM, or other safety concerns
Strong humoral and cellular immune responses
Detectable through 12 months post -vaccination; boosting observed with 1- year
 revaccination
RSV-A & RSV -B nAb responses similar across age groups, including
 those ≥ 80 years old
Immunogenicity
Concomitant 
Administration Pre-specified immunogenicity criteria met & and no new safety signals observed 
with concomitant administration of mRNA -1345 with influenza vaccine or mRNA -
COVID -19 vaccineSummary
NE-48
THANK YOU! Investigators
Study site personnel
Laboratory personnel
Most importantly, the individuals who 
participated in these trials