Protective association of 13-valent pneumococcal conjugate vaccination against experimental carriage determined by 1-year post-vaccination re-challenge with Streptococcus pneumoniae serotype 6B in Blantyre, Malawi

Background
In Malawi, childhood pneumococcal conjugate vaccination has not achieved expected herd protection despite more than 10 years since the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Vaccine efficacy and longevity of protection are crucial in achieving herd protection. We previously found that PCV13 offers immediate protection from experimental pneumococcal carriage in Malawian adults, but of uncertain duration. Using a pre-specified study protocol, we aimed to determine longevity of protection of PCV13 vaccination against experimental human pneumococcal carriage measured by one-year post-vaccination homotypic Streptococcus pneumoniae serotype 6B re-challenge in healthy Malawian adults.

Methods
We re-recruited all eligible participants available at one-year post-vaccination follow-up from a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (SPN6B, strain BHN418) among healthy adults (aged 18-40 years) in Blantyre, Malawi, one year after vaccination. Participants were re-challenged intranasally with 80,000 colony-forming units (CFUs) of SPN6B per naris. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal
wash at 2, 7, and 14 days. Vaccine efficacy was estimated using a log-binomial model adjusting for prior experimental SPN6B carriage, prior natural carriage of any serotype, and prior inoculation dose.

Findings
Participant recruitment started on 10 May 2022 and the final visit was completed on 22 August 2023. 137 participants completed the study protocol after being re-recruited (57 PCV13, 80 placebo). In an adjusted model, there was a 73% protective effect of PCV13 vaccination against experimental pneumococcus serotype 6B carriage following re-challenge (RR 0.27, 95% CI 0.08-0.98, p = 0.047). Prior experimental serotype 6B carriage reduced vaccine protective effect, and even reversed it (RR 2.20, 95% CI 0.85-5.67, p = 0.10). The effect of PCV13 vaccination was reduced within prior serotype 6B carriers (RR 8.95, 95% CI 2.27-35.33, p = 0.002) and prior natural pneumococcal carriers (RR 14.31, 95% CI (1.65, 124.20), p = 0.016). Lastly, in the placebo but not vaccine arm, experimental pneumococcal carriage rate was lower after nasal re-challenge compared to the primary challenge (12 [15.0%] of 80 vs 30 [28.3%] of 106; McNemar’s test p=0.031) indicating an immunising effect of the primary challenge.

Interpretation
The study indicates that PCV13 vaccination has a role in preventing pneumococcal
carriage for at least one year, with strong interaction with natural carriage events. This suggests that the inability to achieve herd protection in Malawi is probably due to factors other than the efficacy or duration of protection of the PCV13 vaccine.