Memory B cell responses induced by pneumococcal conjugate vaccine schedules with fewer doses: analysis of a randomised-controlled trial in Viet Nam.

The use of pneumococcal conjugate vaccine (PCV) schedules with fewer doses are being considered to reduce costs and improve access, particularly in low- and middle-income countries. While several studies have assessed their immunogenicity, there are limited data on their potential for long-term immune protection, as assessed by pneumococcal serotype-specific memory B cell (Bmem) responses. This current study reports secondary outcome data that aims to compare Bmem responses following reduced-dose (0 + 1 and 1 + 1) schedules of PCV10 and PCV13 in Vietnamese infants from our randomised-controlled trial (trial registration number NCT03098628). Following vaccination at 12 months of age, Bmem levels for most serotypes peaked seven days post-vaccination and were higher in magnitude for the 1 + 1 than 0 + 1 schedules and for PCV13 than PCV10. Furthermore, Bmem did not wane as rapidly as IgG levels by 24 months of age. Further studies are needed to assess the use of Bmem as markers of long-term protection against pneumococcal carriage and disease, which is crucial to generate data for immunisation program decision-making.

Immunogenicity, safety, and reactogenicity of a half- versus full-dose BNT162b2 (Pfizer-BioNTech) booster following a two-dose ChAdOx1 nCoV-19, BBIBP-CorV, or Gam-COVID-Vac priming schedule in Mongolia: a randomised, controlled, non-inferiority trial.

Background: COVID-19 vaccine booster doses restore vaccine effectiveness lost from waning immunity and emerging variants. Fractional dosing may improve COVID-19 booster acceptability and uptake and will reduce the per-dose cost of COVID-19 booster programmes. We sought to quantify the immunogenicity, reactogenicity, and safety of a half-dose BNT162b2 (Pfizer-BioNTech) booster relative to the standard formulation. Methods: This randomised, controlled, non-inferiority trial recruited adults in Mongolia primed with a two-dose homologous ChAdOx1 nCov-19 (Oxford-AstraZeneca, n = 129 participants), BBIBP-CorV (Sinopharm (Beijing), n = 399), or Gam-COVID-Vac (Gamaleya, n = 70) schedule. Participants were randomised (1:1) to receive a 15 µg (half-dose) or 30 µg (full-dose) BNT162b2 booster. Participants and study staff assessing reactogenicity were blinded up to day 28. Co-primary endpoints were Wuhan-Hu-1 anti-spike S1 IgG seroresponse 28 days post-boosting and reactogenicity within 7 days of boosting. The non-inferiority margin for the absolute difference in seroresponse was -10%. Differences in seroresponse were estimated from logistic regression with marginal standardisation. Geometric mean ratios of IgG were also estimated. ClinicalTrials.gov Identifier: NCT05265065. Findings: Between May 27th and September 30th, 2022, 601 participants were randomized to full-dose BNT162b2 (n = 300) or half-dose (n = 301). 598 were included in safety analyses, and 587 in immunological analyses. The frequency of grade 3-4 reactions was similar between arms (half-dose: 4/299 [1.3%]; full-dose: 6/299 [2.0%]). Across all severity grades, half-dose recipients reported fewer local and systemic reactions (60% versus 72% and 25% versus 32%, respectively). Seroresponse was 84.7% (250/295) and 86.6% (253/292) in the half-dose and full-dose arms, respectively (Difference: -2.8%; 95% CI -7.7, 2.1). Geometric mean IgG titres were similar in those receiving full and half-dose boosters for the ChAdOx1 and BBIBP-CorV primed groups, but lower in the half-dose arm in Gam-COVID-Vac-primed participants (GMR: 0.71; 95% CI 0.54, 0.93). Interpretation: Half-dose BNT162b2 boosting elicited an immune response that was non-inferior to a full-dose, with fewer reactions, in adults primed with ChAdOx1 nCov-19 or BBIBP-CorV. Half-dose boosting may not be suitable in adults primed with Gam-COVID-Vac. Half-dose BNT162b2 boosting may be considered in populations primed with ChAdOx1 nCov-19 or BBIBP-CorV. Funding: Coalition for Epidemic Preparedness Innovations (CEPI).