Pneumococcal conjugate vaccine: A glimpse into current recommendations

Pneumococcal conjugate vaccine: A glimpse into current recommendationsLatest revision | Image Credit: © AdobeStock_74430853 - © AdobeStock_74430853 - stock.adobe.com.

Streptococcus pneumoniae, a lancet-shaped, gram-positive, facultative anaerobe,is a common cause of acute otitis media, sinusitis, community-acquired pneumonia, and pediatric conjunctivitis.^1,2 Additionally, S pneumoniae is the most common cause of bacterial meningitis in infants and children aged 2 months to 11 years in the US.² Complications of S pneumoniae include hemolytic uremic syndrome and pleural empyema. Infants, young children, and older adults are at the highest risk for pneumococcal infection, and viral illnesses, such as influenza, may predispose sensitive groups to pneumococcal infection.² Pneumococci are common bacteria of the respiratory tract. There are over 100 known serotypes of S pneumoniae, and while most of these serotypes have the potential to cause disease in humans, the majority of pneumococcal disease is caused by a minority of the serotypes.¹

Current vaccinations available for S pneumoniae are made of either pneumococcal polysaccharides, such as the PPSV23 vaccine, or pneumococcal conjugates, such as the pneumococcal conjugated vaccine-13 (PCV13) and the recently approved PCV15 and PCV20. Although PPSV23 covers more serotypes, the conjugated vaccine provides better immunogenicity than the polysaccharide version. Since the introduction of the earlier versions of the conjugated PCV7 (2000) and PCV13 (2010), racial disparities with pneumococcal infection have decreased and overall invasive pneumococcal disease caused by serotypes contained within the PCV13 vaccine have decreased. Furthermore, rates of penicillin-nonsusceptible and ceftriaxone-resistant isolates have decreased since the introduction of PCV7 and PCV13. However, recent reports of invasive pneumococcal disease in Alaskan Native and Southwestern American Indian populations have reported incidences of disease caused by serotypes not covered in the PCV13 vaccine.²

From February to October 2021, the Advisory Committee on Immunization Practices (ACIP) analyzed the pneumococcal disease epidemiology and immunology of PCV15 and PCV20 in the adult population. PCV15 included the serotypes covered in PCV13 plus serotypes 22F and 33F, and PCV20 included serotypes 8, 10A, 11A, 12F, and 15B in addition to the 15 serotypes in PCV15. This review found that PCV15 provided noninferior immunogenicity of the 13 shared serotypes compared with PCV13 and a significantly greater response to 3 serotypes, including serotype 3, which is shared between PCV13 and PCV15, as well as the PCV15-specific serotypes 22F and 33F. PCV20, when compared with PCV13, met noninferiority criteria for immunogenicity for all 13 shared serotypes in adults aged 60 years and older. When compared with PPSV23, PCV20 had a higher percentage of seroresponders to 6 of 7 shared, non-PCV13 serotypes.³

In the phase 3 trial PNEU-PED (NCT03893448), conducted from 2019 to 2021, PCV15 showed noninferiority of immunogenicity to PCV13 in 12 of the 13 shared serotypes with superior immunogenicity to serotypes 3, 22F, and 33F in healthy infants. Adverse effects of PCV15 were comparable to those seen with PCV13.⁴ In June 2022, the FDA approved the use of PCV15 in pediatric patients aged 6 weeks and older.^5,6 The phase 3 trial comparing PCV13 and PCV20 was conducted from 2020 to 2022 and demonstrated noninferior immunogenic responses to the 13 shared serotypes and a larger response to the 7 additional serotypes included in the PCV20 vaccination. Safety profiles of PCV20 were comparable to those of PCV13.⁷ PCV20 was subsequently approved in April 2023 (Table 1).^6,9

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In a 2023 surveillance of invasive pneumococcal disease, including bacteremic pneumonia, meningitis, and bacteremia, in pediatric patients aged 5 years and younger, serotypes 19A, 3, 10A, and 12F were the most common cause of disease. Serotype 19A is covered in PCV13. Serotype 3 was identified as a common cause of invasive disease in countries with short-term and long-term utilization of PCV10 or PCV13 vaccinations. Several rationales are proposed, including a decline in vaccination rates and developing resistance.⁹ Serotypes 10A and 12F are novel to the PCV15 and PCV20 vaccines compared with the historically used products. Given that there are reports of these serotypes causing a significant number of cases of invasive disease, incorporation of these serotypes into vaccines and the preferential utilization of the newer vaccines has the potential to decrease rates of invasive pneumococcal disease even further. (Table 2)^9,10

In summary, the PCV15 and PCV20 vaccinations provide a wider coverage of pneumococcal serotypes than the previously utilized conjugated pneumococcal vaccines. The expanded coverage of vaccinations includes 22F and 33F in PCV15 and 22F, 33F, 15B, 10A, 11A, 12F, and 8 in PCV20. A further decline in rates of invasive pneumococcal disease is anticipated in the near future. No studies directly compare PCV15 with PCV20 at this time. As practice evolves, the Centers for Disease Control and Prevention should always be consulted (https://www.cdc.gov/vaccines/acip/recommendations.html).

References:

1. Clinical overview of pneumococcal disease. Centers for Disease Control and Prevention. February 6, 2024. Accessed September 1, 2024. https://www.cdc.gov/pneumococcal/hcp/clinical-overview/index.html

2. Streptococcus pneumoniae (pneumococcal) infections. In: Kimberlin DW, Banerjee R, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2024-2027 Report of the Committee on Infectious Diseases. 33rd ed. American Academy of Pediatrics; 2024. Accessed July 11, 2024. https://publications.aap.org/redbook/book/755/chapter-abstract/14082214/Streptococcus-pneumoniae-Pneumococcal

3. Kobayashi M, Farrar JL, Gierke R, et al. 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. MMWR Morb Mortal Wkly Rep. 2022;71:109-117. doi:10.15585/mmwr.mm7104a1

4. Lupinacci R, Rupp R, Wittawatmongkol O, et al. A phase 3, multicenter, randomized, double-blind, active-comparator-controlled study to evaluate the safety, tolerability, and immunogenicity of a 4-dose regimen of V114, a 15-valent pneumococcal conjugate vaccine, in healthy infants (PNEU-PED). Vaccine. 2023;41(5):1142-1152. doi:10.1016/j.vaccine.2022.12.054

5. Vaxneuvance. Prescribing information. Merck Sharp & Dohme LLC; 2024. Accessed July 11, 2024. https://www.merck.com/product/usa/pi_circulars/v/vaxneuvance/vaxneuvance_pi.pdf

6. Farrar JL, Gierke R, Andrejko KL, et al. Use of 20-valent pneumococcal conjugate vaccine among U.S. children: updated recommendations of the Advisory Committee on Immunization Practice ― United States, 2023: supplementary report. MMWR Morb Mortal Wkly Rep. 2023;72(39):1072. doi:10.15585/mmwr.mm7239a5

7. Klein NP, Peyrani P, Yacisin K, 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;39(38):5428-5435. doi:10.1016/j.vaccine.2021.07.004

8. Prevnar 20. Prescribing information. Pfizer Inc; 2023. Accessed July 11, 2024. https://labeling.pfizer.com/ShowLabeling.aspx?id=15428

9. Grant LR, Slack MPE, Theilacker C, et al. Distribution of serotypes causing invasive pneumococcal disease in children from high-income countries and the impact of pediatric pneumococcal vaccination. Clin Infect Dis. 2023;76(3):e1062-e1070. doi:10.1093/cid/ciac475

10. ACIP updates: recommendations for use of 20-valent pneumococcal conjugate vaccine in children ― United States, 2023. MMWR Morb Mortal Wkly Rep. 2023;72:1072. doi:10.15585/mmwr.mm7239a5