Plasma cell and memory B cell responses following immunisation with polysaccharide and conjugate quadrivalent meningococcal ACYW135 vaccines in healthy adult volunteers.
Ramasamy MN., Haworth K., Clutterbuck EAC., Nickells T., Snape MD., John T., Blanchard-Rohner G., Po None., Pollard AJ.
Background Neisseria meningitidis is a leading cause of meningitis and septicaemia. The development of quadrivalent protein-polysaccharide conjugate vaccines against serogroups A, C, W135 & Y offers the possibility of broader protection against the organism across all age groups. Methods We conducted an open-label randomised clinical trial in 150 healthy adult volunteers aged 18-70. Participants were randomised to receive either 2 doses of a conjugate quadrivalent ACWY vaccine 28 days apart (MenConj-MenConj), or one dose of a polysaccharide quadrivalent ACWY vaccine followed by one dose of a conjugate quadrivalent ACWY vaccine 28 days later (MenPS-MenConj). Meningococcal polysaccharide-specific memory B cells were enumerated in peripheral blood at days 0, 28 and 56 by cultured EliSpot assay. Results Median memory cell numbers were similar at baseline in the two groups (medians of 1.0-3.0 cells per million cultured lymphocytes). By 56 days, median memory cell numbers were higher in the MenConj-MenConj group than in the MenPS-MenConj group (7.0, 8.0, 3.0 and 3.0 cells per million cultured lymphocytes for serogroups A, C, W135 & Y respectively vs. 4.5, 3.0, 2.0 and 2.0). Conclusions Two doses of conjugate vaccine generate larger memory responses than conjugate vaccine preceded by polysaccharide vaccine. This probably represents polysaccharide driven hypo-responsiveness, but might indicate differences in the magnitude or phenotype of cells responding to the two different vaccines.