PRIORITIZING PNEUMOCOCCAL VACCINE AND ITS HEALTH IMPLICATIONS.pptx

The United States uses 2 types of pneumococcal vaccines. Each individual vaccine helps protect against different serotypes of pneumococcal bacteria.

Pneumococcal conjugate vaccines (PCVs)
PCV15
PCV20
PCV21
Pneumococcal polysaccharide vaccine
PPSV23

1. Emerging need  of Adult Vaccination Ghia CJ, et al. Health Serv Res Manag Epidemiol . 2021;8:23333928211030791 . VPD: Vaccine-preventable disease AMR: Anti Microbial Resistance Increasing burden of VPDs in adults in India >95% of VPD-associated deaths Age Recommended for people aged ≥50 years age. Comorbidities in the aging population 2- to 4-fold increase in the risk of community-acquired pneumonia. Emerging drug resistance Immunosenescence Immunosenescence after age of 50 years. Increasing trends of AMR. Gupta M et al . Need and Rationale of the Adult Immunisation in India: A Review. Preventive Medicine Research & Reviews. :2024. | DOI: 10.4103/PMRR.PMRR_13_24

2. 1 . Ghoshal AG, et al. J Assoc Physicians India . 2016;64:8–11. 2. Eshwara VK, et al. Indian J Med Res. 2020;151(4):287–302. 3 . Prasad P, Bhat S. Lung India. 2017;34(5):491–492. 4. Dey AB et al. Natl Med J India. 1997;10(4):169–172. Burden of Pneumococcal Disease CAP: Community-acquired pneumonia; DALY: Disability-adjusted life year; GBD: Global burden of disease; WHO: World Health Organization. 23%: Global burden 36%: WHO regional pneumonia burden 1 25% of hospitalized patients are affected by bacteremic pneumonia 1 13%–55% prevalence of S. pneumoniae in CAP infection 2-4 Images for representation purpose only Incidence of pneumococcal disease in India

3. ~40‑45 million cases/year of community‑acquired pneumonia (CAP) Pneumococcus in CAP - 30‑40% of cases Hospitalization rates falls within range of 10% to 30%, I ncreases with age to 60‑70% in elderly individuals Disease burden of pneumonia in India Koul PA et al. Lung India 2024;41:307-17.

4. Aged population Adults aged 50 years or older 1 Chronic illness Conditions like CHD,CLD,CKD, l ung diseases, diabetes, or alcoholism 2 Mass gatherings Travellers spending time in crowded areas or are in close contact with children Immunocompromised population People with medical conditions such as cancer, damaged/absent spleen Who are at a higher risk of developing P neumococcal disease? Source: 1. Sharma OP. Indian recommendations for vaccination in older adults. Delhi: Geriatric society of India . 2015; 2. Risk factors and Transmission of Pneumococcal Disease, CDC CHD; Chronic Heart Disease;CLD:Chronic Liver Diseas;CKD : Chronic Kidney Disease

5. Impact of various risk factors on incidence of pneumococcal disease Grant LR,  Open Forum Infectious Diseases . 2023; 10 (5). Rates of pneumococcal disease tend to increase with age and risk profile. Higher incidence rates were observed in higher age group patients with different comorbidities. Increased Risk of Pneumococcal Disease in At-Risk and High-Risk Populations

6. Adults who are at increased risk for P neumococcal diseases including severe infections Risk factors for IPD Alcoholism Cerebrospinal fluid leak Chronic heart, kidney, liver, or lung disease Cigarette smoking Cochlear implant Decreased immune function from disease or drugs (i.e., immunocompromising condition) Diabetes mellitus Immuno-compromising conditions Chronic renal failure or nephrotic syndrome Congenital or acquired asplenia or splenic dysfunction Congenital or acquired immunodeficiency Disease or condition treated with immunosuppressive drugs or radiation therapy* HIV infection Sickle cell disease or other hemoglobinopathies *including Hodgkin disease, leukemias , lymphomas, malignant neoplasms, and solid organ transplant Clinical Overview of Pneumococcal Disease | Pneumococcal | CDC

7. Prevalence and duration of health conditions reported as worsened by pneumonia Health condition Reported worsening (%) Days until return to baseline Asthma 23.0 24.8 COPD 24.4 52.4 Chronic bronchitis 12.2 32.8 Chronic emphysema 8.6 60.0 High blood pressure 20.1 21.6 Heart disease 5.9 38.7 Diabetes 9.8 18.0 Others 8.5 48.3 A content-valid questionnaire assessing pneumonia symptoms and comorbid conditions was administered online to adults aged ≥50 years with a recent diagnosis of CAP Existing Health Conditions Can Be Worsened by Pneumonia CAP : Community-acquired pneumonia; COPD : Chronic obstructive pulmonary disease. Wyrwich KW, et al. Patient Relat Outcome Meas. 2015;6:215-223.

8. Clinical effectiveness of Pneumococcal Conjugated Vaccine (PCV) 13

9. Study description 1 A double-blind, randomised , parallel-group, placebo-controlled vaccine efficacy trial 84,496 Immunocompetent adults aged 65 and older 59 sites throughout the Netherlands conducted surveillance 3.93 years ―median duration of follow-up 2 had ≥1 comorbid condition that increased their risk for pneumococcal disease 1,2 42.3 % of patients The Efficacy of PCV13 in the Community-Acquired Pneumonia Immunization Trial in Adults ( CAPiTA ) 25.4% heart disease 15.1% lung disease or asthma 12.5% type 1 and type 2 diabetes mellitus 12.3% reported smoking at baseline Secondary Prevention of a first episode of confirmed nonbacteremic and non-invasive vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease  Primary Prevention of a first episode of confirmed vaccine-type CAP CAP : Community-acquired pneumonia . 1 . Bonten MJ, et al. N Engl J Med. 2015;372(12):1114-1125 . 2. Prevnar 13 ( Pneumococcal 13-valent Conjugate Vaccine [ Diphtheria CRM 197 Protein]) Prescribing Information, Wyeth Pharmaceuticals LLC, 2019. Study endpoints 1

10. 10 20 30 40 50 60 70 80 80 100 Vaccine efficacy (%) Primary endpoint: Prevention of the first episode of VT-CAP 46% P <0.001 45% P = 0.007 75% P <0.001 Secondary endpoint: Prevention of a first episode of VT non- bacteraemic / non-invasive CAP Secondary endpoint: Prevention of the first episode of VT-IPD Reduction in pneumococcal disease with PCV13 1,2 PCV13 Demonstrated Efficacy Against a First Episode of VT-CAP in Adults Aged 65 Years and Older In one of the largest vaccine trials ever conducted in adults 65 years and older, PCV13 demonstrated efficacy against VT non-invasive pneumococcal pneumonia and invasive disease CAP : Community-acquired pneumonia; CAPiTA : Community-Acquired Pneumonia Immunization Trial in Adults; VT : Vaccine type. 1. Bonten MJ, et al. N Engl J Med. 2015;372(12):1114-1125 . 2. Prevnar 13 ( Pneumococcal 13-valent Conjugate Vaccine [ Diphtheria CRM 197 Protein]) Prescribing Information, Wyeth Pharmaceuticals LLC, 2019.

11. BODE Index: Body-mass index, Airflow Obstruction, Dyspnea, and Exercise Capacity; COPD: Chronic obstructive pulmonary disease; PCV13: 13-valent pneumococcal conjugate vaccine; PPV23: 23-valent pneumococcal polysaccharide vaccine . Ignatova GL , et al . Sci Rep . 2021;11(1):15948. Prevention of pneumonia Pneumonia after 5 years was reported in 3.3% of patients receiving PCV13 and 47% receiving PPV23. Reduced rate of COPD exacerbations COPD exacerbations were seen in 23.6% of PCV13 recipients and 81.3% of PPV23 recipients after 5 years. Improved quality of life PCV13 vaccination significantly reduced and maintained the BODE index over 5 years. Positive effects last 5 years with PCV13 but decline from year 2 with PPV23. Only PCV13 shows persistent effectiveness over the 5-year follow-up Patients administered PPV23 exhibit notably elevated pneumonia risks. PCV13 Showed Persistent Clinical Effectiveness in Reducing Rates of Pneumonia and COPD Exacerbations Images for representation purpose only PCV13 reduces pneumonia and COPD exacerbations while maintaining the Body-mass index, Airflow Obstruction, Dyspnea, and Exercise Capacity (BODE) index over 5 years versus PPV23.

12. Post hoc analysis of the CAPiTA study, a double blind, randomized controlled trial PCV13 yielded 89.5% VE in patients with DM in preventing first episode of VT-CAP. VE: Vaccine effectiveness VT-CAP: Vaccine type Community acquired pneumonia Huijts SM, van Werkhoven CH, Bolkenbaas M, Grobbee DE, Bonten MJM. Post-hoc analysis of a randomized controlled trial: Diabetes mellitus modifies the efficacy of the 13-valent pneumococcal conjugate vaccine in elderly. Vaccine. 2017 Aug 3;35(34):4444-4449. doi : 10.1016/j.vaccine.2017.01.071.

13. Effectiveness of PCV13 in Patients With Acute COPD Exacerbations: HOPE COPD Study The HOPE COPD study P ost hoc cross‑sectional analytical study 120 hospitalized COPD patients with acute exacerbation Mean age: 72.43 years±8.8 PCV13: n=60 Unvaccinated : n= 60 Multilobar consolidation Primary endpoint: Secondary endpoint: R espiratory failure, fever , inflammatory markers, ICU care, vasopressor shock Venkitakrishnan R, et al. J Adv Lung Health. 2024;4(2):77–85. COPD: Chronic obstructive pulmonary disease; HOPE COPD: Health Outcomes of Pneumococcal Vaccination in COPD; ICU: Intensive Care Unit; PCV13: 13-valent pneumococcal conjugate vaccine. Images for representation purpose only To evaluate exacerbation severity in PCV13 conjugate vaccine vs. unvaccinated COPD subjects hospitalized with acute exacerbation.

14. PCV13 Pre-Immunization Lessens Exacerbation Severity, Improves Clinical Outcomes: HOPE COPD Study Multilobar consolidation occurred substantially less in the vaccinated group. The vaccinated group showed a significantly lower incidence of fever, leukocytosis, and elevated CRP . Differences in parameters of exacerbation severity between vaccinated and unvaccinated patients. Venkitakrishnan R, et al. J Adv Lung Health. 2024;4(2 ):77–85. COPD: Chronic obstructive pulmonary disease; CRP: C-reactive protein; HOPE COPD: Health Outcomes of Pneumococcal Vaccination in COPD; ICU: Intensive Care Unit; PCV13: 13-valent pneumococcal conjugate vaccine. Adapted from: Venkitakrishnan R, et al. J Adv Lung Health. 2024;4(2):77–85. p<0.0001 p<0.0001 p =0.0002 P=0.0040 Clinical outcomes Pre-immunization with PCV13 alleviates exacerbation severity in hospitalized COPD patients.

15. PCV13 Pre-Immunization Improves COPD Hospital Outcomes: HOPE COPD Study p=0.04 30% 58.3% Vaccinated patients needed ICU admission Unvaccinated patients needed ICU admission Parameters​ Vaccinated patients​ Unvaccinated patients​ p-value ​ Length of ICU stay (days)​ 0.67±1.11 ​ 1.77±1.89 ​ 0.001​ Length of hospital stay (days)​ 4.50±1.64 ​ 5.47±2.03 ​ 0.005​ COPD: Chronic obstructive pulmonary disease; HOPE COPD: Health Outcomes of Pneumococcal Vaccination in COPD; ICU: Intensive care unit; PCV13: 13-valent pneumococcal conjugate vaccine. Venkitakrishnan R, et al . ERJ Open Res . 2023;9(3). Hospital outcomes COPD patients with prior PCV13 showed improved outcomes during hospitalization for acute exacerbation.

16. What are the prevention options for pneumococcal diseases?

17. Pneumococcal vaccines approved for adults in India PPSV23 PCV13 Pneumococcal disease PPSV23 : 23‑valent pneumococcal polysaccharide vaccine, PCV13 : 13‑valent pneumococcal conjugate vaccine

18. Pneumococcal vaccines approved for adults in India Polysaccharide Vaccine 1,2 Conjugate Vaccine 1-4 T-cell–independent immune response that cannot be boosted Contain polysaccharide antigens Stimulate B cells to produce antibodies T-cell–dependent immune response and booster response with revaccination Contain polysaccharide antigens covalently linked to a carrier protein Stimulate T cells to help B cells produce antibodies and generate immune memory Conjugation allows for stimulation of the T-cell–dependent immune response necessary for immune memory 1. Siegrist CA. In: Plotkin et al, eds. Vaccines. 5th ed. Philadelphia, PA: Saunders Elsevier; 2008:17-36. 2. Pollard AJ, et al. Nat Rev Immunol . 2009;9(3):213-220. 3. Clutterbuck EA, et al. Immunology. 2006;119(3):328-337. 4. de Roux A, et al. Clin Infect Dis. 2008;46(7):1015-1023.

19. Global and Indian Recommendations on Pneumococcal Vaccine

20. Risk-based ACIP recommendation: Adults aged 19-64 years of age 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 should receive a pneumococcal vaccine Rationale: 1-The risk of pneumococcal disease increases with age 2-The risk of comorbidities increases from 50 years 3-Comorbidities increase the risk of pneumococcal disease 4-Pneumococcal disease worsens short term and long term outcomes in patients with comorbidities 1. IDSE November 2021. ACIP Recommends Pneumococcal Vaccines for Certain Immunocompromised Adults https://www.idse.net/Bacterial-Infections/Article/11-21/ACIP-Recommends-Pneumococcal-Vaccines-for-Certain-Immunocompromised-Adults/65169 . 2. Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2022 at https://www.cdc.gov/mmwr/volumes/71/wr/mm7104a1.htm . (URLs accessed January 2023). Early (>/=50) recommendation for use of PCV in adults Pneumococcal vaccination is recommended for all adults ≥50 and for all high-risk conditions except during pregnancy.

21. 21 IPD Incidence Rates in the US by Age Group, 2007–2022 Data from CDC Active Bacterial Core surveillance CDC = Centers for Disease Control and Prevention; IPD = invasive pneumococcal disease; PCV = pneumococcal conjugate vaccine; SCDM = shared clinical decision-making Adapted from Kobayashi M. Summary of Work Group interpretation of EtR and policy options. Presentation at the October 2024, ACIP Meeting. October 23, 2024. https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-Kobayashi-Pneumococcal-508.pdf [accessed Oct 23, 2024] Age d <5 years Age d ≥65 years Post-COVID 10 20 40 45 Cases per 100,000 population PCV13: children 5 2007 Year 2008 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2009 35 30 25 15 Age d 50–64 years PCV13: Adults ≥ 65 PCV13: Adults ≥ 65 based on SCDM

22. 22 IPD Mortality Rate in Adults Aged ≥65 Years Has Approached the Rate of Adults Aged 50–64 Years Data from CDC Active Bacterial Core surveillance CDC = Centers for Disease Control and Prevention; IPD = invasive pneumococcal disease Adapted from Kobayashi M. Summary of Work Group interpretation of EtR and policy options. Presentation at the October 2024, ACIP Meeting. October 23, 2024. https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-Kobayashi-Pneumococcal-508.pdf [accessed Oct 23, 2024] Aged 50–64 years Overall Aged ≥65 years 5. 10.0 20.0 Rates (deaths) per 100,000 population Year 2000 2005 2010 2015 2020 1 5.0

23. Vaccine Coverage Tends to Be Lower in Younger Adults Even With an Age-Based Recommendation *Represents those who received ≥2 doses. † Receipt of any pneumococcal vaccine dose among those with risk-based indications Adapted from Kobayashi M. Summary of Work Group interpretation of EtR and policy options. Presentation at the October 2024, ACIP Meeting. October 23, 2024. https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-Kobayashi-Pneumococcal-508.pdf [accessed Oct 23, 2024] 23 25.2% 40.6% 51.5% 73.8% 20.1% (60–64) 22.8% (≥65) 37.3% † 69.7% COVID-19 20 40 80 100 Percent of eligible population vaccinated 10 70 60 50 30 Influenza Recombinant Zoster vaccine* Pneumococcal 90 12.2% (50–59) Adults aged ≥ 65 years Adults aged 50–64 years Vaccines

24. Compared with vaccine coverage in adults aged ≥65 years, pneumococcal vaccine coverage in adults aged 50–64 years with risk-based indication was disproportionately lower 1. 2. 3. 4. Week ending May 11, 2024. Vaccine coverage with the updated 2023- 2024 COVID- 19 vaccine, defined as receipt of at least one vaccination since September 2023. Week ending May 11, 2024. Vaccine coverage for the 2023-2024 influenza season Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC , % represents those who received at least 2 doses BRFSS 2022 data, % represents receipt of any pneumococcal vaccine dose 50–64 yrs ≥65 yrs (50–64 yrs)/ (≥65 yrs) COVID-19 1 25.2% 40.6% 0.62 Influenza 2 51.5% 73.8% 0.70 Recombinant Zoster Vaccine 3 12.2% (50–59) 20.1% (60–64) 22.8% Pneumococcal 4 37.3%* 69.7% 0.54 *Receipt of any pneumococcal vaccine dose among those with risk-based indications

25. Aged 19–49 years Aged 50–64 years Aged ≥65 years >80% of adult IPD cases have ≥1 risk-based indication for a pneumococcal vaccination Proportion of US Adult IPD Cases With a Risk-Based Indication, 2018−2021 82 % PCV = pneumococcal conjugate vaccine Adapted from Kobayashi M. Summary of Work Group interpretation of EtR and policy options. Presentation at the October 2024, ACIP Meeting. October 23, 2024. https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-Kobayashi-Pneumococcal-508.pdf [accessed Oct 23, 2024] A High Proportion of Adults Aged ≥50 Years with IPD Have ≥1 Risk Condition for ​Pneumococcal Vaccination

26. Key considerations: factors supporting lowering the PCV age-based recommendation to age ≥50 years *Note that these are models that assumed that another vaccine dose is given later in life to ensure older adults are protected from disease The relatively high burden of pneumococcal disease in adults aged 50–64 years, particularly among those with risk conditions Potential for improved vaccine uptake through an age- based recommendation, which is easier to implement compared with the current risk- based recommendation Potential to reduce pneumococcal disease incidence in demographic groups experiencing the highest burden Projected health benefits from economic models despite increased net costs

27. Outside of India, Guidelines From the CDC Support Pneumococcal Vaccination in Adults Aged ≥50 Years and 19-49 Years With Risk Conditions 27 a Age 18 to 49 years with risk conditions in the Indian Consensus Guideline. CDC=US Centers for Disease Control and Prevention. 1. US Centers for Disease Control and Prevention. October 23, 2024. Accessed November 8, 2024. https://www.cdc.gov/media/releases/2024/s1023-pneumococcal-vaccination.html 2. Mathur G, et al. Accessed October 17, 2024. https://www.emvac.in/wp-content/uploads/2024/06/Adult Vaccination-Booklet.pdf 3. US Centers for Disease Control and Prevention. October 26, 2024. Accessed November 13, 2024. https://www.cdc.gov/pneumococcal/vaccines/index.html In October 2024, the CDC Advisory Committee on Immunisation Practices recommended lowering the age of pneumococcal vaccination from 65 to 50 years 1 Because older adults are at increased risk for pneumococcal disease, lowering the age for pneumococcal vaccination gives more adults the opportunity to protect themselves at the age when risk of infection substantially increases Pneumococcal vaccination recommendations by age Indian Consensus Guideline 2 CDC 3 Age 19 to 49 years with risk conditions Age ≥50 years

28. 28 Indian consensus guideline on adult immunization. Available at: https://apiindia.org/reader/immunization . Accessed on: 05 August 24. The Indian Consensus on Adult Immunization Guidelines is a pivotal initiative developed by the Association of Physicians of India (API) in collaboration with representatives from 13 diverse medical societies . In a landscape where existing adult immunization guidelines vary based on age and risk-based conditions, the need for a unified approach becomes imperative. The medical societies include: Indian Association of Preventive & Social Medicine (IAPSM) Heart Failure Association of India (HFAI) Indian Rheumatology Association (IRA) Clinical Infectious Disease Society (CIDS) Cardiological Society of India (CSI) Indian Society of Critical Care Medicine (ISCCM) Federation of Obstetric & Gynecological Societies of India (FOGSI) Indian Chest Society (ICS) Indian Society of Nephrology (ISN) Indian Society of Oncology (ISO) Geriatric Society of India (GSI) Indian Medical Association (IMA) Geriatric Society of India (GSI) The emergence of new medical challenges, coupled with the increasing geriatric population, necessitates a proactive approach to immunization. These guidelines aim to bridge the existing gaps in understanding and implementation by offering a consolidated approach to provide clarity for adult vaccination decision-making. Indian Consensus Guideline on Adult Immunization

29. ≥50 years  Age 18-49 years Pregnancy  Immuno- compromised  HIV Infection  Asplenia,  complement deficiency  CKD/HD Heart/ lung disease/ alcoholism CLD DM HCP Traveler  Mass gathering R – R R R R R R R AR R R R : Recommended | AR : Additional risk factors Key considerations: Recommended for all, especially those with increased risk irrespective of age (for adults) 1 dose of PCV13 followed by PPSV23 1 year later Above 50 years: PCV13 followed by PPSV23, 1 year At risk: PCV13 followed by PPSV23, 1 year High Risk: PCV13 followed by PPSV23, 8 weeks later API: Association of Physicians of India; CLD: Chronic liver disease; CKD: Chronic kidney disease; DM: Diabetes mellitus; HCP: Health care professional; HD: Hemodialysis; HIV: Human immunodeficiency virus; PCV13: 13-valent pneumococcal conjugate vaccine; PPSV23: 23-valent pneumococcal polysaccharide vaccine Indian consensus guideline on adult immunization. Available at: https://apiindia.org/reader/immunization .Accessed on: 15 May 24. Pneumococcal vaccination is recommended for all adults ≥50 and for all high-risk conditions except during pregnancy. Indian Consensus Guideline on Adult Immunization

30. Vaccination Schedule for Health Care Personnel Indian consensus guideline on adult immunization. Available at: https://apiindia.org/reader/immunization . Accessed on: 10 June 24.

31. Rao CR, Kamath VG, Nadda A, Parida SP, Sharma N, Goel K, et al. IAPSM’s position paper on Pneumococcal Vaccine (PCV) for adult immunization in India. Indian J Community Med. 2024;49:S132-8.

32. For all healthcare professionals – whether they provide vaccinations or not – to take steps to help ensure that their adult patients are fully immunised . Standards for Adult Immunisation Practice Assess Assess the vaccination status of patients at every clinical encounter Recommend Strongly recommend needed vaccines Administer / refer Offer vaccinations at the same visit or schedule on suitable date Document Document vaccinations Incorporating vaccination as a part of patient management Standards for Adult Immunization Practices | CDC

33. Strongly RECOMMEND vaccines that patients need SHARE HIGHLIGHT ADDRESS REMIND EXPLAIN The tailored reasons why the recommended vaccine is right for the patient depending on patient’s age, health status, lifestyle, occupation, or other risk factors. Positive experiences with vaccines (personal or in your practice), as appropriate, to reinforce the benefits and strengthen confidence in vaccination. Patient questions and any concerns about the vaccine, including side effects, safety, and vaccine effectiveness in plain and understandable language. Patients that vaccines protect them and their loved ones from many common and serious diseases The potential costs of getting the disease, including serious health effects, time lost (such as missing work or family obligations), and financial costs. Standards for Adult Immunization Practices | CDC [Internet]. Cdc.gov. 2016 [cited 14 Feb 2022]. Available from: https://www.cdc.gov/vaccines/hcp/adults/for-practice/standards/index.html Vaccine Recommendation Cdc.gov. [cited 18 February 2022]. Available from: https://www.cdc.gov/vaccines/hcp/adults/downloads/standards-immz-practice-recommendation.pdf

34. New Generation Pneumococcal Vaccine

35. Pneumococcal Vaccines Have Typically Evolved by Adding New Serotypes to the Existing Ones 35 PPSV4 1 PPSV14 1 PPSV23 1 Age >2 years PCV 13 1 PCV15 3,4 PCV 20 5,6,9 1945 1977 1983 2011 US 2011 EMA 2010 India 2021 US 2021 EMA 2021 US 2022 EMA 2025 India Pneumococcal Polysaccharide Vaccines (PPSV) Pneumococcal Conjugate Vaccines (PCVs) Adult Indications Vaccine serotypes are typically selected based on epidemiological and clinical relevance 10 The approach of adding serotypes ensures both maintenance and expanded coverage of some of the most relevant serotypes 10 PCV15 is not approved for use in India PCV 20 is currently not marketed in India

36. The Importance of the Serotypes Included in PCV 20 36

37. PCV13 2 PCV 20 Is Built on the Proven Platform of PCV7 and PCV 13 37 *The amount of polysaccharide in PCV was 2µg for all serotypes except for 6B - 4µg . 1. Prevenar 20 India label: LPDPRV022025, PfLEET number: 2025-0096628 dated 2nd Feb 2025 . 2. Full India PI available on request 3. Prevenar [summary of product characteristics]. Kent, United Kingdom: Pfizer Limited; 2017. PCV 20 is modeled after PCV7 and PCV13, containing 1-3 : The same components as PCV 13, including the 13 capsular polysaccharides each individually conjugated to CRM 197 , plus polysaccharides for 7 additional serotypes, each also conjugated to CRM 197 The same vaccine excipients as PCV13 The amount of polysaccharide (2.2 μ g/dose) selected for each new serotype (8, 10A, 11A, 12F, 15B, 22F, 33F) contained in PCV20 mirrors the approach taken for the addition of the 6 new serotypes when developing PCV 13 4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A 19A 8 10A 11A 12F 15B 22F 33F 2 .2 μ g 4.4 μ g 2 .2 μ g 2 .2 μ g 2 .2 μ g 2 .2 μ g 2 .2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g 2 . 2 μ g CRM 197 PCV20 1 PCV7 3* PCV 20 is currently not marketed in India