GRADE: 20-valent pneumococcal conjugate vaccine (PCV20) for adults aged 19–64 years with underlying medical conditions or other risk factors

Grading of Recommendations, Assessment, Development, and Evaluation

About

  • CDC vaccine recommendations are developed using an explicit evidence-based method based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Introduction

On October 21, 2021, the ACIP recommended use of 20-valent pneumococcal conjugate vaccine (PCV20 [Prevnar 20, Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.]) alone or 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme Corp.]) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23) [Pneumovax23, Merck Sharp & Dohme Corp Inc.]) for all adults aged ≥65 years, and for adults aged 19–64 years with certain underlying medical conditions or other risk factors*, who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown. A systematic review and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach was employed to guide ACIP’s deliberations regarding use of these vaccines.

Introduction Footnote

*Alcoholism, chronic heart/liver/lung disease, chronic renal failure, cigarette smoking, cochlear implant, congenital or acquired asplenia, CSF leak, diabetes mellitus, generalized malignancy, HIV, Hodgkin disease, immunodeficiency, iatrogenic immunosuppression, leukemia, lymphoma, multiple myeloma, nephrotic syndrome, solid organ transplants, or sickle cell disease or other hemoglobinopathies.

Methods

A systematic literature search was completed to review all available evidence on the immunogenicity and safety of PCV15 and PCV20 among age groups for which the vaccines were approved. Since only immunogenicity and safety data were available for PCV15 or PCV20, the search included PCV13 and PPSV23 efficacy or effectiveness studies to help interpret PCV15 and PCV20 immunogenicity study findings. Literature search for evidence on both PCV15 and PCV20 was done simultaneously given the similarities in the policy questions and given that use of both PCV15 and PCV20 were considered by the ACIP simultaneously. GRADE assessment was performed for PCV15 and PCV20 studies only. As a basis for the GRADE analysis, the policy question consisting of the population, intervention, comparison, and outcomes of interest was defined (Table 1).

Table 1: Policy question and definition of the Population, Intervention, Comparison, and Outcome for GRADE analysis

Policy question:
Should PCV20 be recommended to US adults aged 19-64 years with immunocompromising or chronic medical conditions?
Population
US adults aged 19-64 years with immunocompromising or chronic medical conditions
Intervention
One dose of PCV20
Comparison
1. PCV13 followed by PPSV23 (immunocompromised adults aged 19-64 years)*
2. PPSV23 (immunocompetent adults with chronic medical conditions aged 19-64 years)
Outcomes
  • Vaccine-type invasive pneumococcal disease, vaccine-type non-bacteremic pneumococcal pneumonia, and vaccine-type pneumococcal mortality)
  • Serious adverse events following immunization

Table 1 Footnote

*Immunocompromised adults include adults with immunocompromising condition (chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, human immunodeficiency virus, Hodgkin disease, leukemia, lymphoma, multiple myeloma, solid organ transplants, congenital or acquired asplenia, sickle cell disease, or other hemoglobinopathies), CSF leak, or cochlear implant; immunocompetent adults are those without these conditions.

Chronic medical conditions include chronic heart/lung/liver disease, diabetes mellitus, alcoholism, and cigarette smoking.

Table 2: Outcomes and Rankings

Outcome Importance* Included in evidence profile
Vaccine-type invasive pneumococcal disease Critical Yes
Vaccine-type non-bacteremic pneumococcal pneumonia Critical Yes
Vaccine-type pneumococcal mortality Critical Yes
Serious adverse events following immunization Critical Yes

Table 2. Footnote

*Three options: 1. Critical; 2. Important but not critical; 3. Not important for decision making

We leveraged a systematic review presented to the World Health Organization Strategic Advisory Group of Experts (SAGE) meeting in October 2020, which included literature up to March 2019 (1). To identify literature published during April 2019 to February 2021, we searched Pubmed, Medline, Embase, CINAHL, Scopus, Epistemonikos and Cochrane library databases. The search terms are included in appendix I. Search results were supplemented by an updated Pubmed search using “V114*”, “PCV15”, “PCV20”. Unpublished data were provided by the vaccine manufacturers.

Studies were included if they presented primary data on PCV20 in adults with underlying medical conditions or other risk factors†. Of the 2,499 titles screened for WHO SAGE and 923 titles screened for the updated review in 2021, 1 unpublished and 2 published PCV20 studies were included in the GRADE analysis (2-4). Characteristics of these studies are presented in appendix II. Beneficial and harmful outcomes for the GRADE assessment were selected by the ACIP Pneumococcal Vaccines Work Group calls and via an email survey in which Work Group members were asked to rank the relative importance of each outcome. Vaccine-type invasive pneumococcal disease, vaccine-type non-bacteremic pneumococcal pneumonia, vaccine-type pneumococcal mortality, and serious adverse events (SAEs) following immunization were deemed to be critical outcomes (Table 2).

Methods Footnote

*V114 is the name used for Merck’s investigational 15-valent pneumococcal conjugate vaccine candidate

Alcoholism, chronic heart/liver/lung disease, chronic renal failure, cigarette smoking, cochlear implant, congenital or acquired asplenia, CSF leak, diabetes mellitus, generalized malignancy, HIV, Hodgkin disease, immunodeficiency, iatrogenic immunosuppression, leukemia, lymphoma, multiple myeloma, nephrotic syndrome, solid organ transplants, or sickle cell disease or other hemoglobinopathies

Table 3a. Summary of Studies Reporting Immunogenicity

Study Age or other characteristic of importance N intervention N comparison Comparator vaccine GMR range* (serotype) GMT/GMR interpretation*,†,§ Absolute difference in % seroresponders
(serotype)
Interpretation of % serorespondners¶,** Study limitations (Risk of Bias)
B7471007 Adults ≥60 years 1435 1420 PCV13 0.76 (6A) to 1.0 (14)
  • PCV20<PCV13 in 12/13 serotypes (= for serotype 14)
  • PCV20 GMTs significantly lower in 5/13
  • Noninferiority criteria met for all 13/13 serotypes
-5.6 (3) to -0.5 (7F)
  • PCV20<PCV13 in 12/13 PCV13 serotypes
  • PCV20 significantly lower in 1/13 serotype (Serotype 3)
Not serious
1433 1383 PCV13+PPSV23 (28-42 day interval between vaccines; 1-month post-PPSV23; only compared the 7 shared non-PCV13 PPSV23/PCV20 serotypes) 0.55 (8) to 3.1 (15B)
  • PCV20>PCV13+PPSV23 in 6/7 non-PCV13 serotypes
  • PCV20 significantly higher in 5/7 serotypes
  • Significantly lower for 1/7 (serotype 8)
  • Noninferiority criteria met for 6/7 serotypes (not met for serotype 8)
-9 (8) to 14 (15B)
  • PCV20>PCV13+PPSV23 in 6/7 non-PCV13 serotypes
  • PCV20 significantly higher in 6/7
  • PCV20 significantly lower in 1/7 (Serotype 8)
Adults 18-49 years 336 993 PCV20 (in 60-64 year or ≥60 year-olds) 1.00 (3) to 4.8 (23F) (18-49 year-olds compared to ≥60 year-olds)
  • GMTs among 18-49 year-olds>GMTs among 60-64 year-olds in 20/20 serotypes
  • 18-49 year-olds GMTs significantly higher in 14/20
  • Noninferiority criteria met for all 20 serotypes
-11.9 (11A) to 16.3 (9V) (in ≥60 year-olds)
  • PCV20 in 18-49 year-olds>PCV20 in ≥60 year-oldsin 18/20 serotypes
  • Significantly higher in 11/20
  • Significantly lower in 1/20 (Serotype 11A)
Hurley 2020 Adults 60-64 years 195-210 194-208 PCV13 0.62 (19F) to 0.90 (6B)
  • PCV20<PCV13 in 13/13 serotypes
  • Significantly lower in 4/13
-9.8 (19F) to 1.3 (6A)
  • PCV20<PCV13 in 12/13 serotypes (all non-significant)
Not serious
185-207 181-204 PCV13+PPSV23 (1-month interval between vaccines; 1-month post-PPSV23; only compared 7 shared non-PCV13 serotypes) 0.64 (8) to 2.64 (10A)
  • PCV20>PCV13+PPPSV23 in 6/7 non-PCV13 serotypes
  • Significantly higher in 3/7
  • PCV20<PCV13+PPSV23, PCV20 significantly lower in 1/7 (8)
-4.9 (8) to 14.7 (10A)
  • PCV20>PCV13+PPPSV23 in 6/7 non-PCV13 serotypes
  • Significantly higher in 2/7
  • PCV20<PCV13+PPSV23 lower in 1/7 (Serotype 8, non- significant)
201-208 196-203 PCV13+PPSV23 (1-month interval between vaccines; 1-month post-PPSV23; only compared 13 shared PCV13 serotypes) 0.50(3) to 0.79(6B)
  • PCV13+PPSV23>PCV20 in 13/13 serotypes
  • PCV20 significantly lower in 9/13
Not Reported Not Reported
Klein 2021 Adults 18-49 years 1463 245 PCV13 0.67 (19F) to 1.00 (14)
  • PCV20<PCV13 in 12/13 serotypes
  • PCV20 significantly lower in 3/13 (1,5,19F)
  • Noninferiority criteria met for all 13/13 serotypes
-7.5 (1) to 1 (14)
  • PCV20<PCV13 in 12/13 serotypes
  • PCV20 significantly lower in 3/13 (Serotypes 1, 5,19F)
Not Serious

Table 3a. Footnotes
GMR=geometric mean ratio, GMT=geometric mean titers, OPA=opsonophagocytic activity, PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine

*GMR (geometric mean ratio) is the ratio of pneumococcal OPA GMTs.Ratio calculated as [GMT (PCV20)] / [GMT (comparator vaccine)].

GMR noninferiority for a serotype was declared if the lower bound of the 2-sided 95% CI for the GMR for that serotype was greater than 0.5 (2-fold criterion).

§If GMR non-inferiority was not assessed, “statistical significance” of GMTs (geometric mean titers) defined as: 95% CI of GMT point estimates did not overlap.

Seroresponse: subjects with ≥4-fold rise in OPA GMT titer 30 days post-vaccination compared to pre-vaccination.

**If seroresponsenon-inferiority was not assessed, “statistical significance” defined as: 95% CI of %serorespondersdid not overlap.

Table 3b. Summary of Studies Reporting Safety

Study Age or other characteristic of importance N intervention N comparison Comparator vaccine Absolute % difference (% SAE PCV20 - % SAE comparator) N related to vaccine Study limitations (Risk of Bias)
B7471007 Adults 60 years and older 1461 1445 PCV13+PPSV23 (6-month observation period) 0.5
(CI overlaps)
0 Not serious
Adults 50-59 334 111 PCV13 (6-month observation period) -0.6
(CI overlaps)
0
Adults 18-49 335 112 PCV13 (6-month observation period) -0.3
(CI overlaps)
0
Hurley, 2020 Adults 60 - 64 years 221 222 PCV13 (1-month observation period) -0.5
(CI overlaps)
0 Not serious
213 214 PCV13+PPSV23 (12-month observation period) -0.9
(CI overlaps)
0
Klein, 2021 Adults 18-49 1463 245 PCV13 (6-month observation period) 0.7 0 Not serious

Table 3b. Footnote
CI= confidence interval, PCV13=13-valent pneumococcal conjugate vaccine, PCV20=20-valent pneumococcal conjugate vaccine, PPSV23=23-valent pneumococcal polysaccharide vaccine, SAE=serious adverse events

Table 4. Grade Summary of Findings Table

Certainty assessment Number of patients Results Certainty Importance
№ of studies (reference) Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Intervention Comparison** Relative effect Absolute effect
Vaccine effectiveness (Vaccine-type invasive pneumococcal disease, Vaccine-type non-bacteremic pneumococcal pneumonia, Vaccine-type pneumococcal mortality)
2 (2-4) Randomized studies Not serious Not serious Very serious*,†,§,¶ Not serious Not serious 3417 2802 PCV20 vs. PCV13: non-inferiority met for all 13 shared serotypes
PCV20 had slightly lower immune responses vs. PCV13 in 13 shared serotypes across studies.
PCV20 vs. PPSV23 (non-PCV13 serotypes): noninferiority met for 6 of 7 serotypes (not met for serotype 8).
PCV20 had greater immune responses vs. PPSV23 for 6 of 7 PCV20 non-PCV13 shared serotypes.
3, Low Critical
Serious adverse events
2 (2-4) Randomized studies Not serious Not serious Not serious Serious†† None 0/3852 0/2172 Non estimable --- 2, Moderate Critical

Table 4. Footnote

*These are all immunogenicity studies and there are no correlates of protection.

B7471007, Klein et al., and Hurley et al. enrolled healthy adults (some with chronic stable conditions, but focus is not those with immunocompromising or chronic medical conditions).

§B7471007 provided primary PCV20 vs PCV13 immunogenicity outcomes for adults ≥60 and then showed non-inferiority for PCV20 in 18-49 year-olds compared to PCV20 in 60-64 year-olds. Did not directly compare immunogenicity of PCV20 vs PCV13 in 18-49 year-olds.

Hurley et al. only enrolled 60-64 year-olds.

**Number of patients based on minimum number included in immunogenicity comparisons presented; some comparisons may have had more patients than this minimum.

††No vaccine-related serious adverse events reported; sample size relatively small.

Table 5. Summary of Evidence for Outcomes of Interest

Outcome Importance Included in evidence profile Certainty
Vaccine-type invasive pneumococcal disease Critical Yes 3, low
Vaccine-type non-bacteremic pneumococcal pneumonia Critical Yes 3, low
Vaccine-type pneumococcal mortality Critical Yes 3, low
Serious adverse events following immunization Critical Yes 2, moderate

Summary

The evidence type for use of PCV20 for adults aged 19–64 years with certain underlying medical conditions or other risk factors was determined to be 3 (low certainty of evidence). The ACIP reviewed the results of both GRADE analysis and the Evidence to Recommendations (EtR) framework in September 2021. In October 2021, the ACIP recommended use of PCV20 for adults aged 19–64 years with certain underlying medical conditions or other risk factors who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown.

Reference

  1. World Health Organization. Strategic Advisory Group of Experts on Immunization 5-7 October 2020. 2020 [cited 2021 July 28]; Available from: https://terrance.who.int/mediacentre/data/sage/SAGE_eYB_October_2020.pdf?ua=1.
  2. Essink B, Sabharwal C, Xu X, Sundaraiyer V, Peng Y, Moyer L, et al. 3. Phase 3 Pivotal Evaluation of 20-valent Pneumococcal Conjugate Vaccine (PCV20) Safety, Tolerability, and Immunologic Noninferiority in Participants 18 Years and Older. Open Forum Infect Dis. 2020;7(Suppl 1):S2-S.
  3. Hurley D, Griffin C, Young M, Scott DA, Pride MW, Scully IL, et al. Safety, Tolerability, and Immunogenicity of a 20-Valent Pneumococcal Conjugate Vaccine (PCV20) in Adults 60 to 64 Years of Age. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2020 Jul 27.
  4. Klein NP, Peyrani P, Yacisin K, Caldwell N, Xu X, Scully IL, et al. A phase 3, randomized, double-blind study to evaluate the immunogenicity and safety of 3 lots of 20-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naive adults 18 through 49 years of age. Vaccine. 2021 Sep 7;39(38):5428-35.

Appendix I. Search Strategies

Database Strategy Run Date Records
Medline
(OVID)
1. streptococcus pneumoniae/
2. (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”).tw,kf.
3. 1 or 2
4. vaccination/ or immunization/ or Vaccines, Conjugate/
5. (vaccine? or vaccination? or immunisation or immunization).tw,kf.
6. 4 or 5
7. Pneumococcal Vaccines/
8. (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”).tw,kf.
9. 7 or 8
10. (3 and 6)
11. 10 or 9
12. comparative effectiveness research/ or treatment outcome/ or Vaccine Potency/
13. (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”).tw,kf.
14. 12 or 13
15. adult/ or aged/ or “aged, 80 and over”/ or frail elderly/
16. (adult? or elderly or elderlies).tw,kf.
17. 15 or 16
18. 11 and 14 and 17
19. (201904* OR 201905* OR 201906* OR 201907* OR 201908* OR 201909* OR 201910* OR 201911* OR 201912* OR 2020* OR 2021*).ed,ep,yr,dp,dt.
20. 17 and 18
02/18/2021 351
Embase
(OVID)
1988-
1. Streptococcus pneumoniae/
2. (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”).tw,kw.
3. 1 or 2
4. vaccination/ or immunization/ or vaccine/
5. (vaccine? or vaccination? or immunisation or immunization).tw,kw.
6. 4 or 5
7. Pneumococcus vaccine/
8. (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”).tw,kw.
9. 7 or 8
10. 3 and 6
11. 9 OR 10
12. comparative effectiveness/ or treatment outcome/
13. (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”).tw,kw.
14. 12 or 13
15. aged/ or adult/ or aged hospital patient/ or frail elderly/ or institutionalized elderly/ or very elderly/
16. (adult? or elderly or elderlies).tw,kw.
17. 15 or 16
18. 11 and 14 and 17
19. (201904* OR 201905* OR 201906* OR 201907* OR 201908* OR 201909* OR 201910* OR 201911* OR 201912* OR 2020* OR 2021*).dc
20. limit 19 to (conference abstracts or embase)
02/18/2021 521


duplicates

=
unique items

Cochrane Library (
(
(pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”):ti,ab
AND
([mh Vaccines] OR [mh Immunization] OR (vaccine# or vaccination# or immunisation or immunization):ti,ab)
)
OR
(MH “Pneumococcal Vaccine”) OR TI (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”) OR AB (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”)
)
AND[mh “Treatment Outcomes”] OR (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”):ti,abAND[mh Adult] OR [mh Aged+] OR (adult# or elderly or elderlies):ti,ab
02/18/2021 56


duplicates

=
unique items

CINAHL
(EbscoHost)
(
(TI (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”) OR AB (pneumococcal or pneumococci or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”)) AND ((MH “Vaccines”) OR (MH “Immunization”) OR TI (vaccine# or vaccination# or immunisation or immunization) OR AB (vaccine# or vaccination# or immunisation or immunization))
OR
(MH “Pneumococcal Vaccine”) OR TI (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”) OR AB (heptavalent or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or pcv10 or “pcv 10” or “13valent” or “13 valent” or pcv13 or “pcv 13” or ppv23 or “ppv 23” or “23 valent” or “23valent”)
)
AND
(MH “Treatment Outcomes”) OR TI (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”) OR AB (efficacy or effectiveness or effects or “immune response” or impact or “treatment outcome”)
AND
((MH “Adult”) OR (MH “Aged+”) OR TI (adult# or elderly or elderlies) OR AB (adult# or elderly or elderlies))Limiters – Published Date: 20190401-20210218; Exclude MEDLINE records
02/18/2021 43


duplicates

=
unique items

Scopus
(for WOS)
(TITLE-ABS-KEY(“heptavalent” or “7 valent” or “7valent” or “pcv 7” or pcv7* or “10 valent” or “10valent” or “pcv10” or “pcv 10” or “13valent” or “13 valent” or “pcv13” or “pcv 13” or “ppv23” or “ppv 23” or “23 valent” or “23valent”) OR (TITLE-ABS-KEY(“vaccine$” or “vaccination$” or “immunisation” or “immunization”) AND TITLE-ABS-KEY(“pneumococcal” or “pneumococci” or “streptococcus pneumonie” or “streptococcus pneumoniae” or “s pneumoniae”))) AND TITLE-ABS-KEY(“adult$” or “elderly” or “elderlies”) AND TITLE-ABS-KEY(“efficacy” or “effectiveness” or “effects” or “immune response” or “impact” or “treatment outcome”)

Limit April 2019 –

02/18/2021 458


duplicates

=
unique items

Epistemonikos Search 1:
(pneumococcal OR pneumococci OR “streptococcus pneumonie” OR “streptococcus pneumoniae” OR “s pneumoniae”) AND (vaccine* OR vaccination* OR immunisation OR immunization) AND (efficacy OR effectiveness OR effects OR “immune response” OR impact OR “treatment outcome”) AND (adult* OR elderly OR elderlies)
– limited to 2019-2021Search 2:
(heptavalent OR “7 valent” OR “7valent” OR “pcv 7” OR pcv7* OR “10 valent” OR “10valent” OR pcv10 OR “pcv 10” OR “13valent” OR “13 valent” OR pcv13 OR “pcv 13” OR ppv23 OR “ppv 23” OR “23 valent” OR “23valent”) AND (efficacy OR effectiveness OR effects OR “immune response” OR impact OR “treatment outcome”) AND (adult* OR elderly OR elderlies)
– limited to 2019-2021
02/18/2021 19 + 10


duplicates

=
unique items

Appendix II. Studies Included in the Review of Evidence

Study Study design Country (or more detail, if needed) Age (measure central tendency – mean/SD) Total population N Intervention N comparison Outcomes Funding source
B7471007 Phase III randomized controlled trial US and Sweden Adults ≥ 18-49 years (34.0, SD 8.8) 448 336 (PCV20) 112 (PCV13) Immunogenicity,
Safety
Pfizer
Adults ≥ 50-59 years (54.9, SD 2.8) 445 334 (PCV20) 111 (PCV13)
Adults ≥ 60 years (64.6, SD 4.8) 2997 1507 (PCV20) 1490 (PCV13+PPSV23)
Hurley, 2020 Phase II randomized controlled trial US Adults 60 – 64 years (62.0, SD 1.4) 444 222 222 Immunogenicity, Safety Pfizer
Klein, 2021 Phase III randomized controlled trial US Adults 18-49 years 1708 1463 245 Immunogenicity,
Safety
Pfizer

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