The effect of pneumococcal conjugate vaccine and pneumococcal polysaccharide vaccine on nasopharyngeal colonisation following human infection challenge with serotype 3 and serotype 6B (PREVENTING PNEUMO 2): a double-masked, randomised, controlled, phase 4 trial.

Summary

In a double-masked human challenge RCT of 407 adults (Spn3) and 243 (Spn6B), PCV13 reduced serotype 3 colonization overall non-significantly, but conferred 29% protection against clade II (RR 0.71). PPV23 showed no protection against clade Iα. At 6 months, PCV13 reduced serotype 6B colonization by 60% (RR 0.40), while PPV23 showed none. No severe adverse events occurred.

Key Findings

• Overall Spn3 colonization: 56% (84/153) PCV13 vs 65% (101/155) placebo; RR 0.84 (95% CI 0.70–1.01), p=0.068.
• Clade-specific effect: protection for clade II (RR 0.71, 95% CI 0.54–0.91; p=0.009), but not clade Iα (RR 1.01, 95% CI 0.77–1.32; p=0.95).
• PPV23 showed no protection against clade Iα (RR 0.84, 95% CI 0.63–1.11; p=0.22).
• At 6 months, PCV13 reduced Spn6B colonization by 60% (RR 0.40, 95% CI 0.22–0.69; p=0.002), whereas PPV23 did not (RR 0.90, 95% CI 0.60–1.34; p=0.60).
• No severe or life-threatening adverse events were observed.

Clinical Implications

Rely less on herd effects for serotype 3; consider direct adult PCV13 (or updated conjugates) to reduce colonization and disease, while recognizing PPV23’s limits. Policymakers should anticipate clade-specific gaps when updating programs.

Limitations

• Healthy adults aged 18–50 may limit generalizability to children, older adults, and high-risk groups.
• Challenge model colonization may not fully mirror natural exposure dynamics; serotype/clade evolution could alter effects over time.

Future Directions

Evaluate updated conjugate formulations targeting Spn3 clade Iα; assess indirect effects and durability across ages; integrate immunologic correlates to inform next-generation vaccine design.