Pivotal Phase 3 Randomized Clinical Trial of the Safety, Tolerability, and Immunogenicity of 20-Valent Pneumococcal Conjugate Vaccine in Adults Aged ≥18 Years

Abstract

Background Pneumococcal conjugate vaccines (PCVs) have significantly reduced pneumococcal disease, but disease from non-PCV serotypes remains. Safety, tolerability, and immunogenicity of a 20-valent PCV (PCV20) were evaluated. Methods This pivotal phase 3, randomized, double-blind study enrolled adults into 3 age groups (≥60, 50-59, 18-49 years) at US and Swedish sites. Participants were randomized to receive one PCV20 or PCV13 dose. After 1 month, participants ≥60 years also received one dose of saline or 23-valent polysaccharide vaccine (PPSV23). Safety assessments included local reactions, systemic events, adverse events, serious adverse events, and newly diagnosed chronic medical conditions. Opsonophagocytic activity (OPA) geometric mean titers (GMTs) 1 month after PCV20 were compared to 13 matched serotypes after PCV13 and to 7 additional serotypes after PPSV23 in participants ≥60 years; noninferiority was declared if lower bound of the 2-sided 95% CI for OPA GMT ratio (PCV20/saline:PCV13/PPSV23 group) was >0.5. PCV20-elicited immune responses in younger participants were also bridged to those in 60-64-year-olds. Results Severity and frequency of prompted local reactions and systemic events were similar after PCV20 or PCV13; no safety concerns were identified. Primary immunogenicity objectives were met, with immune responses after PCV20 noninferior to 13 matched serotypes after PCV13 and to 6 additional PPSV23 serotypes in participants ≥60 years; serotype 8 missed the statistical noninferiority criterion. PCV20 induced robust responses to all 20 vaccine serotypes across age groups. Conclusions PCV20 was safe and well tolerated, with comparable immunogenicity to PCV13/PPSV23. PCV20 is anticipated to expand protection against pneumococcal disease in adults.

Pneumococcal vaccination—A literature review and practice guideline update

“…Other side effects noted from phase 3 studies include fatigue and headache. Overall, the safety of the PCV20 vaccine is comparable to that of PCV13 in immunocompetent adults 18 years of age and older 58,61–64 . Absolute contraindications to the receipt of the PCV20 vaccine include severe allergic reactions, such as anaphylaxis, to any component of the PCV20 vaccine or to diphtheria toxoid, which is a component of the vaccine 58 .…”

“…Absolute contraindications to the receipt of the PCV20 vaccine include severe allergic reactions, such as anaphylaxis, to any component of the PCV20 vaccine or to diphtheria toxoid, which is a component of the vaccine 58 . Unfortunately, safety of the PCV20 vaccine has not yet been assessed in those with immunocompromising conditions, as this patient population was excluded from phase 2 and 3 studies 61–64 . There are also no safety data in patients under the age of 18 or those who are pregnant or breastfeeding.…”

“…58 Unfortunately, safety of the PCV20 vaccine has not yet been assessed in those with immunocompromising conditions, as this patient population was excluded from phase 2 and 3 studies. [61][62][63][64] There are also no safety data in patients under the age of 18 or those who are pregnant or breastfeeding.…”

Thoughts on Pneumococcal Vaccination for the Adult Individuals with Autoimmune Diseases

“…Although the some data showed the immunological and clinical safety of PCV15 and PCV20 [36,37], administration of PCV15 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged ≥50 years [38]. More significant study results by PCV15 and PCV20 in both basic and clinical fields will be expected especially for the prevention of pneumococcal diseases in these patients.…”

Pneumococcal vaccination for adults

“…[30][31][32][33] The vaccination was safe and well tolerated; however, in some studies, a larger proportion of participants who received PCV15 reported injection-site pain when compared with participants who received PCV13. 28,33 ■ Current pneumococcal vaccine recommendations The most recent recommendations for pneumococcal vaccination in adults include two options for those who have never received a PCV: 1) one dose of PCV20 or 2) one dose of PCV15 followed in 1 year by one dose of PPSV23 (see Pneumococcal vaccination recommendations in adults). 19 Pneumococcal vaccination is recommended for all adults age 65 and older as well as for individuals age 19 and older with certain underlying medical conditions (see Indications for early pneumococcal vaccination in adults age ≥19 years).…”