Use of 15-Valent Pneumococcal Conjugate Vaccine and 20-Valent …
Pneumococcal disease incidence in adults. During 2018–2019, the incidence of all IPD in adults aged ≥65 years was 24 per 100,000 population (Figure), and PCV13 serotypes accounted for 27% of cases; additional serotypes unique to PCV15,*** PCV20,††† and PPSV23§§§ caused 15%, 27%, and 35% of IPD, respectively. In adults aged 19–64 years with certain underlying conditions, PCV13 serotypes accounted for 30% of IPD; serotypes unique to PCV15, PCV20, and PPSV23 caused 13%, 28%, and 43% of IPD, respectively. Estimates of pneumococcal pneumonia incidence are more variable. Annual incidence among U.S. adults aged <65 and ≥65 years hospitalized with community-acquired pneumonia was estimated at 126–422 and 847–3,365 per 100,000, respectively, during 2010–2016 (10). In a multisite study of adults hospitalized with community-acquired pneumonia, 4.6% of cases were caused by PCV13 serotypes, and 1.4% and 3.3% were caused by additional serotypes included in PCV15 and PCV20, respectively (11).
PCV15 immunogenicity. PCV15 contains pneumococcal polysaccharide serotypes 22F and 33F in addition to the PCV13 serotypes, conjugated to CRM197 (genetically detoxified diphtheria toxin) (9). Phase II and III randomized controlled trials (RCTs) evaluated the immunogenicity and safety of a dose of PCV15 compared with a dose of PCV13 in healthy adults aged ≥50 years (12–14), adults aged 18–49 years who are Native American (a population with higher rates of IPD than the general U.S. population) (15) or with ≥1 risk condition for pneumococcal disease (16), and adults aged ≥18 years with HIV infection (17). Serotype-specific functional antibody responses were measured 1 month after vaccination using an opsonophagocytic activity (OPA) assay. Correlates of protection have not been established for adults. In one phase III RCT among adults aged ≥50 years, PCV15 met the noninferiority criteria¶¶¶ compared with PCV13 for the 13 shared serotypes and had statistically significantly greater response**** for shared serotype 3 and PCV15-unique serotypes 22F and 33F (14). In studies that evaluated the immunogenicity of PCV15 or PCV13 followed by PPSV23 2–12 months later (16–18), persons who received PCV15 had numerically similar or higher OPA geometric mean antibody titers (GMTs) for 9–13†††† shared PCV13 serotypes and a higher percentage of seroresponders§§§§ for 5–11 shared serotypes compared with persons who received PCV13 when measured 1 month after receipt of PPSV23.
PCV15 safety. Safety of PCV15 was assessed in seven RCTs with 5,630 participants aged ≥18 years who received 1 dose of PCV15. Most participants were immunocompetent; however, one study included 302 adults with HIV infection. Participants included those vaccinated with PPSV23 ≥1 year before receiving PCV15, those who received PCV15 followed by PPSV23, and those who received PCV15 concomitantly with a seasonal inactivated quadrivalent influenza vaccine (QIV). The most frequently reported adverse reactions were injection site pain, fatigue, and myalgia. The rates of serious adverse events (SAEs) within 6 months of vaccination were 2.5% among PCV15 recipients and 2.4% among PCV13 recipients. No SAEs or deaths were considered to be related to the study vaccines (9,19).
PCV20 immunogenicity. PCV20 contains pneumococcal polysaccharide serotypes 8, 10A, 11A, 12F, 15B, 22F, and 33F, in addition to PCV13 serotypes, conjugated to CRM197 (20). A phase II study among adults aged 60–64 years and two phase III RCTs among adults aged ≥18 years evaluated immunogenicity and safety of PCV20 compared with PCV13 and with PPSV23 for the seven additional serotypes included in PCV20 (21–23). These studies included adults with stable medical conditions, but none included adults with immunocompromising conditions. Compared with PCV13 recipients, PCV20 recipients elicited responses that met noninferiority criteria¶¶¶¶ for all 13 serotypes in a phase III trial among adults aged ≥60 years (21); however, PCV20 recipients appeared to have lower GMTs and included a lower percentage of seroresponders to 12–13 of the 13 PCV13-shared serotypes (21,22). Compared with PPSV23 recipients, PCV20 recipients had numerically higher GMTs and a higher percentage of seroresponders to six of seven (excluding serotype 8) shared non-PCV13 serotypes (21,23); noninferiority criteria were met for those six serotypes (21).
PCV20 safety. Safety of PCV20 was assessed in six trials among immunocompetent adults aged ≥18 years that included a total of 4,552 participants who received PCV20. Participants included those who were naïve to pneumococcal vaccination and those who had previously received pneumococcal vaccination. The most frequently reported adverse reactions were injection site pain, muscle pain, fatigue, headache, and joint pain. SAEs reported within 6 months after vaccination occurred among 1.5% of PCV20 recipients and 1.8% among controls. No SAEs or deaths were considered to be related to study vaccines (20,24).
Intervals between PCV and PPSV23. Findings from eight immunogenicity studies that evaluated the immune response after a sequence of 7-valent PCV, PCV13, or PCV15 followed by PPSV23 administered at intervals of 2, 6, or 12 months or 3–4 years were reviewed (16–18,25–29). Three studies comparing intervals ranging from 2 to 6 months between administration of PCV and PPSV23 found no significant difference in immunogenicity measured after PPSV23 receipt, although reactogenicity tended to be higher with shorter intervals (25–29). In a study that compared antibody responses to 1 dose of PCV13 with responses to PCV13 followed by PPSV23 1 year apart, the immune responses following PPSV23 were significantly lower compared with the responses after a dose of PCV13 for eight of 12 common serotypes (27). In another study that compared antibody response to 1 dose of PCV13 with responses to PCV13 followed by PPSV23 approximately 4 years apart, the immune responses following PPSV23 were significantly higher for seven of 12 common serotypes (26). These findings suggested that longer intervals between administration of PCV and PPSV23 might improve immunogenicity in immunocompetent adults, although a direct comparison between a 1- versus 4-year interval was not made.
Cost-effectiveness. Economic models assessed cost-effectiveness of the new policy options compared with existing recommendations (30). Three economic models assessed PCV20 alone for all adults aged ≥65 years; cost-effectiveness estimates ranged from cost-saving***** to $39,000 per quality-adjusted life-year (QALY) gained. Two economic models assessed use of PCV15 in series with PPSV23 for all adults aged ≥65 years; estimates ranged from cost-saving to $282,000 per QALY gained. The CDC model found cost savings in all scenarios for use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years. Cost estimates of policy options for adults aged 19–64 years with certain underlying medical conditions ranged from $11,000 to $292,000 per QALY gained for PCV20 and from $250,000 to $656,000 for PCV15 in series with PPSV23.
Summary. Use of PCV20 alone or PCV15 in series with PPSV23 is expected to reduce pneumococcal disease incidence in adults aged ≥65 years and in those aged 19–64 years with certain underlying conditions. Findings from studies suggested that the immunogenicity and safety of PCV20 alone or PCV15 in series with PPSV23 were comparable to PCV13 alone or PCV13 in series with PPSV23. Cost-effectiveness studies demonstrated that use of PCV20 alone or PCV15 in series with PPSV23 for adults at age 65 years was cost-saving. The new policy simplifies adult pneumococcal vaccine recommendations (Table 1) and is expected to improve vaccine coverage among adults and prevent more pneumococcal disease. An amendment to recommend PCV20 for all adults aged ≥50 years instead of age ≥65 years was considered but rejected (Table 2). A summary of Work Group deliberations on use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years or adults aged 19–64 years with certain underlying conditions is available in the EtR tables.