Adjuvant system AS02V enhances humoral and cellular immune responses to pneumococcal protein PhtD vaccine in healthy young and older adults: Randomised, controlled trials

Background: The protection elicited by polysaccharide pneumococcal vaccines against community-acquired pneumonia in older adults remains debatable. Alternative vaccine targets include well-conserved pneumococcal protein antigens, such as pneumococcal histidine triad protein D (PhtD). Objective: To evaluate humoral and cellular immune responses and safety/reactogenicity following immunisation with PhtD vaccine with or without adjuvant (alum or AS02(V)) in older (>= 65 years) and young (18-45 years) healthy adults. Methods: Two phase single-blind, parallel-group studies were conducted in 150 older and 147 young adults. Participants were randomised to receive 2 doses (months 0 and 2) of PhtD 30 mu g, PhtD 10 mu g plus alum, PhtD 30 mu g plus alum, PhtD 10 mu g plus AS02(V) or PhtD 30 mu g plus AS02(V), or the 23-valent polysaccharide pneumococcal vaccine (23PPV) at month 0 with placebo (saline solution) at month 2. Safety/reactogenicity was assessed. PhtD-specific antibody, T cell and memory B cell responses were evaluated. Results: Solicited adverse events were more common in young participants and with adjuvanted vaccines. No vaccine-related serious adverse events were reported. Although anti-PhtD geometric mean antibody concentrations (GMCs) were consistently lower in the older adult cohort than in young adults, GMCs in the older cohort following PhtD 30 mu g plus AS02(V) were comparable to those induced by plain PhtD or PhtD 30 mu g plus alum in the young cohort. Compared with alum adjuvant, AS02(V) adjuvant system was associated with an increased frequency of PhtD-specific CD4 cells in both cohorts and a significantly higher specific memory B cell response in the older cohort, similar to responses obtained in the young cohort. Conclusion: The improved immune response to PhtD vaccine containing the AS02(V) adjuvant system in comparison to alum suggests that the reduced immune response to vaccines in older adults can be partially restored to the response level observed in young adults. (C) 2013 Elsevier Ltd. All rights reserved.