The changing landscape of adult pneumococcal vaccines
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Although vaccines have reduced the burden of pneumococcal disease, pneumonia due to Streptococcus pneumoniae and invasive pneumococcal disease remains prevalent.
Two pneumococcal conjugate vaccines (PCVs) — PCV15 and PCV20 — are available for both children and adults. Following the introduction of PCVs into infant immunization programs, there was a substantial drop in pediatric invasive pneumococcal disease (IPD), along with a modest drop in adult disease through reduced transmission. Since the introduction of PCVs, the burden of IPD has shifted to adults, often caused by serotypes not in current vaccines. Because the epidemiology of pneumococcal disease varies between these populations, there was a need for an adult-specific pneumococcal vaccine.
PCV21: A new vaccine for adults
The recently approved PCV21 was developed specifically to target the pneumococcal serotypes that cause 85% of IPD in adults aged 65 years or older. This includes 30% attributed to eight serotypes in PCV21 that are not in any other currently approved vaccines.
In a prevalence study of pneumococcal pneumonia and serotype distribution conducted from 2018 to 2022 in Tennessee and Georgia, a serotype contained in PCV21 — but not PCV15 or PCV20 — was detected in 4.1% of patients, accounting for 38% of serotype detections.
PCV21 is also different than other PCVs because it is formulated without an adjuvant, which increases immune response in children but not in adults.
The vaccine was initially evaluated in a phase 1/2 randomized controlled trial against the 23-valent pneumococcal polysaccharide vaccine (PPSV23), which has the highest number of serotypes in common with PCV21.
In phase 1, researchers compared two different sized doses of PCV21 — 2 g per pneumococcal polysaccharide (PnP) or 4 g per PnP — with PPSV23. The phase 2 portion continued with PCV21 at 4 g per PnP and PPSV23.
The researchers found that PCV21 was noninferior to PPSV23 for 12 shared serotypes and superior for nine unique serotypes contained in PCV21. The most common injection site reaction was pain (46% for PCV21 vs. 38% for PPSV23) in phase 2, and the most common systemic event was fatigue (19% vs. 12%).
The randomized controlled STRIDE-3 trial evaluated the safety, tolerability and immunogenicity of PCV21 compared with PCV20 in adults. It was divided into two cohorts: adults aged 50 years or older and adults aged 18 to 49 years.
The researchers found that PCV21 was noninferior to PCV20 for the serotypes common in both vaccines and superior to PCV20 for all serotypes unique to PCV21 except 15C. There were good immune responses against serotype 15C, but it did not meet the prespecified superiority criteria, possibly because of cross-reactivity between 15B (PCV20) and 15C (PCV21).
There was evidence of cross-reactive immune response in the PCV21 group to 15B (from 15C) and in both groups to 6C (from 6A). Younger adults had generally higher immune responses compared with older adults, and there was a generally lower — though adequate — immune response to both vaccines with increasing age. Adverse events and tolerability were similar between the vaccines, with the most common injection site adverse event being pain and most common systemic event being fatigue and headache.
After the FDA approved the vaccine on June 17 for adults aged 18 years or older, the CDC’s Advisory Committee on Immunization Practices voted unanimously on June 27 to recommend a single dose of PCV21 in the following populations:
- adults aged 65 years or older who have not previously received a pneumococcal conjugate vaccine or whose previous vaccination history is unknown;
- adults aged 19 to 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; and
- adults aged 19 years or older who started their pneumococcal vaccine series with PCV13 but have not received all recommended PPSV23 doses.
Additionally, shared clinical decision-making is recommended regarding use of a supplemental dose of PCV20 or PCV21 for adults aged 65 years or older who have completed their vaccine series with both PCV13 and PPSV23.
The recent changes in pneumococcal vaccination recommendations have made it difficult for clinicians to know which vaccine should be given and when. The CDC created a website and app called PneumoRecs VaxAdvisor to help clinicians quickly and easily determine which pneumococcal vaccines a patient needs and when.
A look at the pipeline
The approval of PCV21 is unlikely to be the last change for pneumococcal vaccination in adults. There are several additional pneumococcal vaccines for adults and children in clinical development.
Pn-MAPS24V is a novel 24-valent pneumococcal vaccine that contains the 13 serotypes in PCV13, an additional 10 included in PPSV23, and 20B. In a phase 1/2 study compared with PCV13, it was safe, well tolerated and exhibited immunogenicity. Among older adults, the functional antibodies were comparable or higher than those shared with PCV13 and PPSV23.
The FDA has granted the vaccine Breakthrough Therapy Designation, and investigators are preparing a phase 3 study. In addition, the vaccine is in phase 2 studies for infants.
Vax-24 is a 24-valent PCV that could cover 70% of IPD serotypes, achieving higher serotype valency and enhanced immune response through the platform it uses. Researchers compared it with PCV20 among adults in a phase 1/2 study and found that it demonstrated similar safety and tolerability. Vax-24 met immunogenicity noninferiority criteria for the 20 shared serotypes, with statistically significant increases compared with PCV20 for a majority of them.
The FDA has also granted Vax-24 Breakthrough Therapy Designation. Researchers have recently completed a phase 2 trial of the vaccine in adults aged 65 years or older, and completed enrollment for phase 2 studies in infants.
Vax-31 is a 31-valent PCV under development by the same company as Vax-24 and uses the same platform. It is designed to provide coverage against about 95% of IPD serotypes in the U.S. adult population. Researchers have completed enrollment in a phase 1/2 trial assessing the vaccine’s safety, tolerability and immunogenicity compared with PCV20 in adults aged 50 years or older. Results are expected in the third quarter of 2024.
IVT PCV-25, a 25-valent PCV, has completed a phase 2 dose-ranging study compared with PCV20 in young adults. If results from the study are satisfactory, its manufacturer plans a phase 2 study in infants and a later phase 2 study in older adults. The manufacturing process of the vaccine allows for a high-conjugate yield and decreases cost, which may help ensure access globally.
Conclusion
There have been significant changes in the availability and recommendations for adult pneumococcal vaccines over the last few years, and it appears the landscape will continue to change over the next few years. Use of the CDC’s new website and app will help clinicians ensure they are following the most up-to-date recommendations for adult pneumococcal vaccination.
References:
- CDC. ACIP presentation slides: June 26-28, 2024 meeting. https://www.cdc.gov/vaccines/acip/meetings/slides-2024-06-26-28.html. Published June 26, 2024. Accessed Aug. 25, 2024.
- CDC. PneumoRecs VaxAdvisor app for vaccine providers. https://www.cdc.gov/pneumococcal/hcp/vaccine-recommendations/app.html. Updated May 31, 2024. Accessed Aug. 25, 2024.
- CDC. Vaccines by disease. https://www.cdc.gov/vaccines/by-disease/index.html. Updated Aug. 10, 2024. Accessed Aug. 25, 2024.
- Chichili GR, et al. Vaccine. 2022;doi:10.1016/j.vaccine.2022.05.079.
- Inventprise completes vaccination of participants in a phase 2 dose ranging study of its 25-valent pneumococcal vaccine candidate. https://inventprise.com/2024/01/02/inventprise-completes-vaccination-of-participants-in-a-phase-2-dose-ranging-study-of-its-25-valent-pneumococcal-vaccine-candidate/. Published Jan. 2, 2024. Accessed Aug. 25, 2024.
- Platt H, et al. Lancet Infect Dis. 2023;doi:10.1016/S1473-3099(22)00526-6.
- Platt HL, et al. Lancet Infect Dis. 2024;doi:10.1016/S1473-3099(24)00344-X.
- Self WH, et al. Clin Infect Dis. 2024;doi:10.1093/cid/ciae316.
- Vaxcyte completes enrollment of phase 1/2 study evaluating VAX-32 for the prevention of invasive pneumococcal disease (IPD) in adults aged 50 and older. https://investors.vaxcyte.com/news-releases/news-release-details/vaxcyte-completes-enrollment-phase-12-study-evaluating-vax-31. Published Jan. 29, 2024. Accessed Aug. 25, 2024.
- Wassil J, et al. Lancet Infect Dis. 2024;doi:10.1016/S1473-3099(23)00572-8.
For more information:
Kelly M. Percival, PharmD, BCPS, BCIDP, is a clinical pharmacy specialist in infectious diseases at the University of Iowa Hospitals & Clinics. Percival can be reached at kelly-percival@uiowa.edu.
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