Abstract:
While pneumococcal conjugate vaccines (PCVs) protect children and older adults against pneumococcal disease caused by most vaccine serotypes, serotype 3 continues to circulate and cause hospitalisations despite being contained in PCV13. In a recent experimental pneumococcal challenge trial, PCV13 vaccination had modest protection against carriage acquisition and no effects on carriage density after intra-nasal challenge with serotype 3 one month after vaccination. Conversely, both carriage acquisition and density were substantially lower when study participants were intra-nasally challenged with serotype 6B six months following PCV13. Here, we explore the association of humoral immune responses induced by PCV13 vaccination with protection from carriage. We show that vaccination with PCV13 induced serotype 3- and 6B capsule polysaccharide (CPS)-specific IgG in blood but only CPS6B-specific IgG was detectable in the nasal mucosa. PCV13-mediated induction of CPS3-specific memory B cells was associated with protection from carriage of serotype 3 although these responses were short-lived. Increased frequencies of CPS6B-specific memory B cells after PCV13 vaccinations were maintained for six months and associated with protection against serotype 6B carriage acquisition. While PCV13 vaccination induced strong humoral immune responses against both CPS3 and CPS6B, differences in magnitude, duration and tissue distribution were associated with differences in carriage protection.
Figure:
