PCV20 and pneumococcal disease: CME notes

Revision notes from this CME, written from the speaker's own slides. The talk ran in four parts, from disease burden through to how PCV20 is used in practice. The slides carried Pfizer product references, and the clinical evidence and recommendations are reproduced here as they were presented.

Part 1

Burden of Pneumococcal Disease

Dr Khizer Hussain Junaidy, MD (Pharmacology), Diabetologist & Bariatric Physician

Pneumococcal disease causes heavy global and Indian mortality, hospitalisation and community-acquired pneumonia, with the highest risk in the elderly and those with comorbidities.

In 2021, S. pneumoniae was responsible for 5,05,000 deaths globally, the highest among all pathogens (GBD 2021). WHO reports that CAP accounts for 4 million deaths per year and 7% of total annual mortality.
For invasive pneumococcal disease (IPD) in adults, the case fatality rate may reach 15% to 20%, and 30% to 40% in the elderly. Pneumonia causes about 6.8 million hospitalisations each year in older adults worldwide.
India contributes 23% of the global pneumonia burden, with case fatality rates of 14% to 30%. S. pneumoniae causes 30% to 55% of CAP in Indian adults.
In a South Indian hospital study (n=408), pneumonia made up 39% of adult IPD cases with a 19% case fatality rate. Pneumonia accounts for 10% to 30% of hospitalisations in India, rising to 60% to 70% in the elderly.
Adults with comorbid conditions have up to 7.7 times higher risk of pneumococcal disease than healthy adults (Shea KM, et al. 2014).
In adults, pneumococcal pneumonia is the commonest form of the disease. In a Spanish CAP cohort of 680 adults aged 18 years and above (2016-2020), about 85% was non-bacteremic and about 15% bacteremic, so most cases will not show up on blood culture.
In 2021, S. pneumoniae caused the largest share of non-COVID lower respiratory infection episodes globally, about 98 million LRIs, spread across all age bands from under 5 years to 70 years and above.

In clinicAsk about comorbidities and age at every adult visit, and treat pneumococcal risk as a routine screening item rather than something raised only after an admission.

Part 2

Why a Higher-Valent Conjugate Vaccine

Dr Khizer Hussain Junaidy, MD (Pharmacology), Diabetologist & Bariatric Physician

Emerging serotypes, short-lived polysaccharide immunity and complex multi-dose schedules created the case for a 20-valent conjugate vaccine built on the PCV13 platform.

Until PCV20, the vaccines approved in India for adults were PCV13 and PPSV23, both used in adults aged 18 years and above and in high-risk groups.
Emerging serotypes carry specific clinical problems. Serotypes 11A, 15B, 22F and 33F show a propensity for antimicrobial resistance; 8 and 12F are linked to outbreaks; 12F, 22F and 33F are common causes of meningitis; 10A and 11A carry a higher case fatality rate; and 8, 10A, 11A, 15B, 22F and 33F tend to cause more severe disease.
Four drivers were given for a higher-valent conjugate vaccine: the spread of emerging serotypes needing broader immunity, poor compliance with multi-dose regimens, the need for durable single-dose protection, and the decline of PPSV23 protection over time requiring revaccination.
PCV20 covers 20 serotypes: 4, 6B, 9V, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, 19A, plus the seven additional serotypes 8, 10A, 11A, 12F, 15B, 22F and 33F.
PCV20 keeps the PCV13 backbone. All serotypes are conjugated to CRM197, the excipients are the same as PCV13, and each new serotype carries 2.2 micrograms of polysaccharide (4.4 micrograms for 6B), consistent with the PCV13 strategy.
Compared with PCV13, PCV20 was reported to add 32.9% IPD serotype coverage, 24.6% hospitalisation-associated serotype coverage and a 1.7 times increase in mortality-causing serotype coverage, with Indian data used for non-invasive isolate coverage.
Indian surveillance data (Jayaraman et al, IPD 2007-2017; Varghese et al, non-invasive pneumonia 2018-2020) showed PCV20 adds 8% IPD coverage and 14% non-invasive CAP coverage over PCV13, and 0.7% non-invasive CAP coverage over PPSV23.

In clinicExplain to patients why serotype coverage matters, and record which pneumococcal vaccine and which year the patient received, so future choices are based on documented history.

Part 3

Clinical Evidence for PCV13 and PCV20

Dr Khizer Hussain Junaidy, MD (Pharmacology), Diabetologist & Bariatric Physician

PCV13 efficacy trials and real-world data underpin PCV20, whose immunogenicity and safety were shown across five phase 3 studies including one in Indian adults.

CAPITA was a randomised, double-blind, placebo-controlled trial in adults 65 years and above (84,496 participants, 42,240 PCV13 and 42,256 placebo, in the Netherlands). Vaccine efficacy was 75% for vaccine-type IPD, 46% for vaccine-type CAP and 45% for non-bacteremic vaccine-type CAP. A post hoc analysis in at-risk adults (N=41,385, median age 72 years) showed 40% efficacy against a first episode of vaccine-type CAP.
The Louisville real-world test-negative study in older US adults showed 73% effectiveness against hospitalised vaccine-type CAP and 70% against non-bacteremic vaccine-type CAP (95% CI 4.1% to 90.7%). Limitations were its observational design, low PCV13 uptake of about 14%, and a small case number (n=68).
PCV20 was licensed by immuno-bridging, which WHO, EMA, US FDA and CDSCO accept. The FDA approved PCV20 on immunogenicity data, with opsonophagocytic activity (OPA) titres as the accepted correlate of protection. A 4-fold rise in OPA titre is taken as significant.
Essink (2022), a pivotal phase 3 trial in 3,902 vaccine-naive adults over 18 years, found PCV20 immunogenicity non-inferior to PCV13 and PPSV23 for 19 of 20 serotypes in those 60 years and above. For serotype 8, additional analyses showed 77.8% of participants had a more than 4-fold rise in OPA titres. Responses in adults 18-59 years were non-inferior to those aged 60-64 years.
Cannon (2021), a phase 3 open-label study in 875 adults 65 years and above with prior vaccination, showed OPA responses to all 20 serotypes in all three cohorts (prior PPSV23 only, prior PCV13 only, prior PCV13 then PPSV23). Responses were highest in PCV13-primed participants and lowest in those with prior PPSV23.
The Indian phase 3 single-arm open-label study (NCT05875727, 8 sites, N=400: 200 aged 18-49 years and 200 aged 50 years and above) gave a single 0.5 mL intramuscular dose. Serotype-specific OPA fold rises at one month were substantial in both cohorts, for example 76.1 and 75.2 for serotype 12F. Most local and systemic events were mild or moderate and no safety concerns were identified.
Cannon (2023) randomised 1,796 US adults 65 years and above and found PCV20 co-administered with quadrivalent inactivated influenza vaccine gave non-inferior responses for all 20 pneumococcal serotypes and all 4 influenza strains, with similar adverse event rates and no vaccine-related serious adverse events.

In clinicOffer PCV20 at the same visit as the seasonal influenza vaccine when both are due, since co-administration data support non-inferior responses and similar tolerability.

Part 4

Using PCV20 in Practice

Dr Khizer Hussain Junaidy, MD (Pharmacology), Diabetologist & Bariatric Physician

Guidelines now support a single PCV20 dose for adults 50 years and above and for younger adults with risk conditions, replacing sequential multi-dose regimens.

CDC ACIP guidance covers adults 50 years and above, and adults 19-49 years with certain underlying medical conditions or risk factors, including specified immunocompromising conditions, cochlear implant or CSF leak. Categories include vaccine-naive or unknown history, PCV13 only at least 1 year prior, PPSV23 only at least 1 year prior, and PCV13 at any age with PPSV23 before 65 years at least 5 years prior.
Indian consensus recommendations (API) for PCV20: adults above 50 years get 1 dose of PCV20 only; at-risk adults get 1 dose of PCV20 only; high-risk adults get 1 dose of PCV20 only. The alternative given is PCV15 followed by PPSV23 after 1 year (8 weeks in high risk), but PCV15 is not approved in India. The older Indian approach was PCV13 followed by PPSV23 after 1 year, or after 8 weeks in high-risk patients.
Indian recommendations list vaccination for adults 50 years and above and for risk groups: immunocompromised, HIV infection, asplenia or complement deficiency, CKD or haemodialysis, heart or lung disease or alcoholism, chronic liver disease, diabetes mellitus, travellers and mass gatherings. Healthcare professionals are listed under additional risk factors. It is recommended for all high-risk conditions except during pregnancy.
The Louisville risk profile shows who to prioritise in practice: COPD 53%, immunocompromised 46%, age 80 years and above 35%, coronary artery disease 35%, congestive heart failure 32% and diabetes 32%.
Safety across Essink (2022), Cannon (2021), Klein (2021, 1,710 adults 18-49 years) and the Indian study (2024) was comparable to PCV13, with no new safety concerns and mostly mild or moderate local and systemic events.
Compared with PPSV23, PCV20 is a T cell-dependent conjugate vaccine that induces immune memory, gives protection in a single dose without sequencing, reduces nasopharyngeal carriage, and is stated to protect against non-invasive pneumonia, where PPSV23 protection is variable.
The deck notes that community outreach, patient education and organised clinic systems are needed to raise adult pneumococcal vaccination rates.

In clinicCheck pneumococcal vaccination status in every adult aged 50 years and above and in younger adults with chronic disease, then give a single PCV20 dose where indicated.