Comparison of short- and long-term humoral immune responses to pneumococcal polysaccharide and glycoconjugate vaccines in an HIV-infected population

Abstract

Immunisation is recommended internationally to protect against pneumococcal infections in HIV-infected adults. However, vaccination schedule designs are mostly based on studies of initial rather than long-term antibody responses. This UK observational study investigated the short- and long-term antibody responses to polysaccharide and glycoconjugate pneumococcal vaccines in an adult HIV-infected cohort. We studied a subgroup of 152 of 839 participants from the AIR (Assessment of Immune Responses to Routine Immunisations in HIV-infected Adults, ISRCTN95588307) studythat had received pneumococcal vaccinationsand had blood samples collected pre- and post-vaccination, as well as at least annually for four subsequent calendar years. Patients received either Pneumovax-23 (PPV, N=89) or Prevenar-13 (PCV, N=63) as their primary vaccine, with immunity assessed by measuring IgG antibody concentrations for 12 pneumococcal polysaccharide serotypes (PnPS). The primary outcome was achieving IgG antibody concentrations above the recommended World Health Organisation (WHO) threshold of 0.35µg/mL for at least 8/12 of the PnPS assessed (WHO≥8/12PnPS). Patients who did not achieve WHO≥8/12PnPS after the primary vaccination were offered further vaccination with PCV; booster vaccinations with PCV were additionally offered to those where antibody levels subsequently fell below the WHO≥8/12PnPS threshold. Patients receiving PCV as their primary pneumococcal vaccine were significantly more likely to achieve WHO≥8/12PnPS after a single vaccine dose than those receiving PPV (54% vs. 33%, p=0.012). This difference persisted following booster vaccination with PCV, with cumulative rates of WHO≥8/12PnPS in those receiving PCV vs. PPV as the primary vaccine of 88% vs. 67% and 100% vs. 85% after receiving up to one and two booster vaccinations, respectively. Where WHO≥8/12PnPS was achieved, this persisted significantly longer in those receiving PCV as their primary vaccine compared to PPV (median: 23.5 vs. 11.1 months; p=0.010). Immunisation with PCV resulted in quantitatively greater antibody responses than immunisation with PPV in a cohort of HIV-infected UK adults. Individuals receiving PCV as their primary vaccine required fewer total pneumococcal vaccine doses to achieve WHO≥8/12PnPS and experienced greater duration of time above this threshold than those with PPV as the primary vaccine. However, the median longevity of both vaccine responses was relatively short, which supports the use of ongoing booster doses using high-valency glycoconjugate vaccines to sustain WHO≥8/12PnPS threshold antibody levels.