05 Pneumococcal Moro 508

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National Center for Emerging and Zoonotic Infectious Diseases
Post -licensure safety surveillance of 20 -valent 
pneumococcal conjugate vaccine (PCV20) 
among U.S. adults in the Vaccine Adverse 
Event Reporting System (VAERS)
Pedro L. Moro, MD, MPH
Immunization Safety Office
Division of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC)
Advisory Committee on Immunization Practices (ACIP)
February 29, 2024
Disclaimer
The findings and conclusions in this presentation are 
those of the author and do not necessarily represent the official position of the CDC
The use of product trade names is for identification purposes only
2
Background on pre -l icensure safety of 20 -valent
pneumococcal conjugate vaccine (PCV20)
Adverse events following PCV20 reported to the Vaccine
A
dverse Event Reporting System (VAERS)
Adverse events of special interest: Guillain -Barr é
Syndrome (GBS)
Summary
3Topics
Background: Pre -licensure clinical trials PCV20
1 Pfizer’s Adult and Pediatric Clinical Trial Programs for 20 -Valent Pneumococcal Conjugate Vaccine Presented at IDWeek  2020. October 21, 2020.
2 Kobayashi M, Farrar JL, Gierke R, et al. Use of 15 -Valent Pneumococcal Conjugate Vaccine and 20 -Valent Pneumococcal Conjugate V accine Among U.S. Adults: Updated Recommendations of the Advisory 
Committee on Immunization Practices — United States, 2022. MMWR Morb  Mortal Wkly  Rep 2022;71:109 –117. DOI: http://dx.doi.org/10.15585/mmwr.mm7104a1  
3 Prevnar20 vaccine insert https://www.fda.gov/vaccines -blood -biologics/vaccines/prevnar -20 Pre-licensure clinical trial data of PCV20 in adults has been reassuring
Six randomized controlled trials in adults aged ≥ 18 years, which included more than 
6,000 participants1,2
Most common adverse reactions were injection site pain, muscle pain, fatigue, headache, and joint pain
2,3
Serious adverse events (SAEs) balanced among vaccinees and controls2
No SAEs or deaths considered to be related to study vaccines3
No cases of Guillain -Barré Syndrome (GBS) identified in prelicensure studies2,3
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Introduction
June 8, 2021 –  PCV20 approved for adults aged ≥ 18 years 
by the FDA
October 20, 2021 – ACIP recommendation
PCV20 for adults aged ≥65
PCV20 for adults aged 19– 64 years with underlying medical 
conditions
FDA: Food and Drug Administration
ACIP: Advisory Committee on Immunization Practices
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Objectives
Describe the safety profile of reports submitted to the
V
accine Adverse Event Reporting System (VAERS) following
PCV20 in
Adults aged ≥65 years
Adults aged 19 –64 years
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VAERS
Strengths
National data 
Accepts reports from anyone
Rapidly detects safety signals 
Can detect rare adverse events
Data available to publicLimitations
Reporting bias 
Inconsistent data quality and 
completeness
Lack of unvaccinated comparison group or denominator
Generally cannot assess causality
•VAERS accepts all reports from all reporters without making judgments on 
causality or judging clinical seriousness of the event
•As a hypothesis generating system, VAERS identifies potential vaccine safety concerns that can be studied in more robust data systems
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Methods – 1: PCV20
Searched VAERS database for U.S. PCV20 reports during:
•October 21, 2021 through December 31, 2023 for adults aged ≥ 19 years 
(19– 64 years and ≥ 65 years)
Signs and symptoms of AEs coded using Medical Dictionary for Regulatory 
Activities (MedDRA)1 Preferred Terms (PTs)
•PTs are not mutually exclusive
•A single report may be assigned more than one PT
Review of serious2 reports and medical records; categorized main diagnosis 
in a MedDRA system organ class  
Case definitions for AESIs: Guillain -Barré Syndrome3
1  https://www.meddra.org/   ; 2 Based on the Code of Federal Regulations 21 CFR 600.80 ; 3Sejvar JJ, et al.  Brighton Collaboration GBS Working Group. Guillain -Barré syndrome and 
Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vacc ine. 2011 Jan 10;29(3):599 -612. doi: 
10.1016/j.vaccine.2010.06.003. Epub 2010 Jun 18. PMID: 206004918
Methods – 2: PCV20
Reporting rates
•Use of doses distributed of PCV20 in the United States during 2022 a nd
2023 (20,
579,720 doses)
Empirical Bayesian data mining (FDA)*
•Used to detect disproportional reporting for the entire post marketing
pe
riod for each product
•Identifies adverse events reported more frequently than expected afterv
accine of interest compared with other vaccines in the VAERS database
•Analysis by age groups and se rious reports.**
9*The presence of disproportionality may not  suggest a safety signal.  Conversely, the absence of disproportionality does not  confirm the absence of a safety signal
nor negate a signal detected by other methods.
**A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that meets any of the following criteria: 1. Resul ts in death; 2. Is life -threatening;
3.Re
quires inpatient hospitalization or prolongation of existing hospitalization; 4. Results in persistent or significant disab ility/incapacity; 5. Is a congenital 
anomaly/birth defect. [FDA regulatory definition; U.S. Code of Federal Regulations, 21 CFR 600.80. Postmarketing reporting of adverse experiences (2014).
Available at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=600.80 ]
PCV20 reports to VAERS, October 2021 –December 2023
19 – 64 years ≥ 65 years ≥ 19 years All2
Characteristics1                      N (%) N (%) N (%) N (%)
Total reports 798 1,178 1,976 2,393
Female 582 (72.9) 846 (71.8) 1,428 (72.3) 1,598 (66.7)
Male 212 (26.6) 330 (28.0) 542 (27.4) 680 (28.4)
Unknown sex 4 (0.5) 1 (0.1) 5 (0.3) 115 (4.8)
Serious reports349 (6.1) 70 (5.9) 119 (6) 149 (6.2)
Deaths 2 (0.3) 9 (0.8) 11 (0.6) 20 (0.8)
Median age [IQR] in years 54 [45,60] 69 [66,75] 65 [56,70]
Median onset interval [IQR] in days 1 [0,2] 1 [0,2] 1 [0,2] 1 [0,1]
Received PCV20 alone 438 (54.9) 711 (60.4) 1,149 (58.1) 1,412 (59.0)
3 Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of hospitalization 
                    or permanent disability 101 U.S. primary reports (foreign reports excluded) ; 2Includes reports in adults aged ≥19 years and 176 reports in persons aged 0 -18 years and 241 reports of unknown age
Most common signs and symptoms1 in reports to VAERS following 
PCV20 in adults aged 19 –64 years, October 2021– December 2023
PCV20  Non- serious (N=749) N (%) 
Injection site reaction 227 (30)
Pain 129 (17)
Erythema 117 (16)
Fever 103 (14)
Pain in extremity 90 (12)
Peripheral swelling 77 (10)
Headache 59 (8)
Skin warm 59 (8)
Fatigue 56 (7)
Arthralgia 52 (7)
1 Coded using the MedDRA  Preferred Terms;  more than one MedDRA  Preferred Term  may be assigned to a single report (i.e., not mutually exclusive) 11PCV20  Serious (N=49) N (%) 
Fever 14 (29)
Dyspnea 12 (25)
Condition aggravated 10 (20)
Cough 10 (20)
Pain 10 (20)
Nausea 9 (18)
Pain in extremity 8 (16)
Dizziness 7 (14)
Fatigue 7 (14)
Headache 7 (14)
Most common signs and symptoms1 in reports to VAERS following 
PCV20 in adults aged ≥65 years, October 2021 –December 2023
PCV20  non- serious (N=1,108) N (%) 
Injection site reaction 417 (35)
Pain 180 (15)
Pain in extremity 162 (14)
Erythema 158 (13)
Fever 135 (12)
Peripheral swelling 103 (9)
Rash 99 (8)
Fatigue 96 (8)
Headache 88 (7)
Pruritus 78 (7)
1 Coded using the MedDRA  Preferred Terms;  more than one MedDRA  Preferred Term  may be assigned to a single report (i.e., not mutually exclusive) 12PCV20 Serious (N=70) N (%)
Pain 14 (20)
Asthenia 13 (19)
Gait disturbance 11 (16)
Guillain Barre Syndrome 11 (16)
Dyspnea 8 (11)
Fatigue 8 (11)
Fever 8 (11)
Chest pain 7 (10)
Death 7 (10)
Dysphagia 7 (10)
Empirical Bayesian data mining (as of January 26, 2024)
Disproportional reporting observed for:
•PT for “Guillain -Barré Syndrome” when limited to serious reports 
(EB05=3.6)1
•When not limited to serious reports EB05=1.87
131 EB05 = Empirical Bayesian data mining threshold for statistical alert; alert considered if EB05 >2.0
Reports to VAERS of Guillain Barre Syndrome after PCV20 vaccination 
among adults aged ≥19 years (as of December 31, 2023)
11 verified reports of Guillain Barré Syndrome2
•Median age (range), years: 66 years (46 -79 y ears)3
•Median time to onset (range), days: 14 days (0 -23)
•4 males, 7 females
•All verified reports met Brighton Collaboration criteria for
G
BS:
–2 were Brighton level 1, 6 were level 2 and 3 were level 3
•Other vaccines during same visit (5 of 11):
– Two RZV (Shingrix)
– One F luad  quadrivalent
– One bivalent mRNA COVID - 19 (Pfizer), HD -IIV4, RSV ( Arexvy )
– One Tdap (Boostrix)Preliminary reports of Guillain 
Barre Syndrome (N=20)
Under 
review1 
(n=4)
Excluded 
based upon 
chart review 
(n=5)
Verified GBS by chart review (n=11) 1 Awaiting medical records
2 One patient had a norovirus infection 1 -2 days before neurological symptoms
3 No GBS reports in persons aged <19 years 14
Reporting rate for GBS after PCV20, 2022 –2023
Reporting rate: 0.5 cases per million doses distributed or 0.9 cases per 
100,000 person- years (background rate 1.72 cases per 100,000 persons -
years) 1
1Gubernot D, et al. U.S.  Population- B ased background incidence rates of medical conditions for use in safety assessment of 
CO VID -19 vaccines.  V accine.  2021;  39:  3666–3677.
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Summary   
VAERS received 1,976 reports after PCV20 in adults during October 2021–
December 2023
•798 in adults aged 19– 64 years; 93.9% non- serious 
•1,178 in adults aged ≥65 years; 94.1% non- serious
Most commonly reported adverse events were injection site (e.g. injection site erythema) and systemic reactions (e.g. fever, headache); consistent 
with findings from pre -licensure studies
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Summary (continued)   
Disproportionate reporting for Guillain -Barré Syndrome (GBS) identified in 
VAERS after PCV20 vaccine (11 verified GBS cases in adults) 
Potential safety signals detected in VAERS need to be evaluated in more robust 
population -based active systems such as the Vaccine Safety Datalink (VSD) or 
Center for Medicaid Services (CMS)
 
Separate studies currently in progress in the VSD (CDC) and CMS (FDA) to assess PCV20 vaccine safety 
CDC and FDA will continue to closely monitor the safety of PCV20 
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Acknowledgements
CDC Immunization Safety Office
•VAERS Team
•Clinical Immunization Safety Assessment (CISA) Project
Food and Drug Administration
•Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation
an
d Research
Butantan  In stitute, Sao Paulo, Brazil
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For more information, contact CDC
1-800- CDC- INFO (232 -4636)
TTY:  1 -888- 232- 6348    www.cdc.gov
The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.
Photo credit: James Gathany 
(https://wwwn.cdc.gov/phil/
Details.aspx?pid=8876)