Pneumococcal 15-Valent Conjugate Vaccine Provides Heightened Protection Against Certain Serotypes Compared With PCV13

V114 (Vaxneuvance; Merck & Co.), a pneumococcal 15-valent conjugate vaccine (PCV15), demonstrated enhanced immunogenicity against serotypes 22F and 33F and had a comparable safety profile with pneumococcal 13-valent conjugate vaccine (PCV13) in healthy infants, according to results from a systematic review and meta-analysis published by investigators in Vaccine: X.¹

Infants are at risk for invasive pneumococcal disease. | Image Credit: © Marina Demidiuk - stock.adobe.com

Infants Remain at Risk for IPD, Necessitating Vaccine Protection

The risks of invasive pneumococcal diseases (IPD) among older adults are well known, but the dangers to young children and infants are just as pertinent. Estimates from the World Health Organization state that infection with Streptococcus pneumoniae (S. pneumoniae), which causes IPD, kills about 300,000 children aged 5 years and younger annually. In a hopeful development, the introduction of PCVs—including PCV13—has since resulted in a meaningful decrease in the rate of IPD and related hospitalizations.^2,3

However, concerns remain regarding the increase in incidence of IPD caused by serotypes not included in current vaccines, specifically serotypes 22F and 33F, which have caused outsized numbers of IPD cases following the introduction of PCV13. In June 2022, V114 was granted approval by the FDA in individuals aged 6 weeks and older for protection against S. pneumoniae serotypes included in PCV13, with the addition of 22F and 33F.^1,4

Studies investigating the immunogenicity of V114 have found superior immunogenicity to serotypes 22F and 33F, contrasting with immune responses to the shared serotypes of PCV13. Given the multiple available PCV options for infants, the authors of this study conducted a systematic review and meta-analysis to evaluate the immunogenicity and safety of PCV15 compared with PCV13, utilizing the most updated evidence from randomized controlled trials (RCTs).^1,4

V114 Provides Enhanced Protection Against Non-PCV13 Serotypes in Infants

After an extensive search of literature through available medical databases, 9 RCTs were ultimately included in the analysis. A total of 9970 infants were included throughout these studies, with 6030 in the V114 group and 3040 in the PCV13 group, according to the authors.¹

Regarding immunogenicity, the proportion of seropositive infants was higher in the PCV13 group compared with the V114 group for most shared serotypes, including 1, 3, 4, 5, 6A, 6B, 7F, 9V, 18C, 19A, 19F, and 23F. Importantly, serotype 3 had a significantly higher seropositivity rate in the V114 group (risk ratio [RR]: 1.71; 95% CI, 1.06-1.29; P = .02). For all other shared serotypes, excluding 3 and 6B, seropositivity rates were not statistically significant.¹

When analyzing additional serotypes specific to V114, the investigators found that the percentage of responders in V114 was above 96% for both serotypes 22F and 33F. This compares favorably with PCV13, which had percentages of responders for serotypes 22F and 33F of 4.77% and 4.01%, respectively, with the pooled analysis of both serotypes significantly in favor of V114. Furthermore, geometric mean concentrations were found to be higher for the additional serotypes unique to V114 in the V114 group compared with the PCV13 group (standardized mean difference [SMD] for serotype 22F: 1.75; 95% CI, 1.61-1.90; P < .0001; SMD for serotype 33F: 1.51; 95% CI, 1.24-1.78; P < .0001).¹

Safety outcomes were analyzed next. There was no statistically meaningful difference between the V114 and PCV13 groups, with an RR of 1.00 (95% CI, 0.99-1.02; P = .38), according to a pooled analysis. Specifically, regarding any adverse effect at the injection site, there was no statistically significant difference between the groups (RR: 1.02; 95% CI, 0.97-1.06; P = .46). However, a review of incidences of erythema, swelling, or pain found an increase in the V114 group compared with PCV13.¹

“By assessing and understanding these vaccines' efficacy and potential adverse effects, public health authorities can better determine which vaccine aligns with local epidemiological needs and ensures optimal coverage,” the study authors wrote in their discussion. “Additionally, the data on possible adverse effects enables healthcare providers to anticipate and manage these reactions, potentially reducing their impact and improving patient outcomes.”¹

REFERENCES

1. Ul Haq MZ, Irfan H, Ullah Shah MS, et al. Immunogenicity, safety and tolerability of 15-valent pneumococcal conjugate vaccine (V114) compared to 13-valent pneumococcal conjugate vaccine (PCV-13) in healthy infants: A systematic review and meta-analysis. Vaccine: X. 2025;24:100654. doi:10.1016/j.jvacx.2025.100654

2. CDC – Pneumococcal disease: Pneumococcal disease surveillance and trends. Last Updated September 9, 2024. Accessed May 29, 2025. https://www.cdc.gov/pneumococcal/php/surveillance/index.html#cdc_generic_section_6-global-trends

3. Olarte L, Barson WJ, Barson RM, et al. Pneumococcal pneumonia requiring hospitalization in US children in the 13-valent pneumococcal conjugate vaccine era. Clin Infect Disease. 2017;64(12):1699-1704. doi:10.1093/cid/cix115

4. FDA. VAXNEUVANCE. Last Updated July 22, 2022. Accessed May 29, 2025. https://www.fda.gov/vaccines-blood-biologics/vaccines/vaxneuvance