Quadrivalent meningococcal polysaccharide and conjugate vaccines: Interim results of a clinical trial in adult volunteers
Ramasamy MN., Clutterbuck EAC., Bowman J., Snape MD., Mpelembue M., Haworth K.
Introduction: 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. We present results of a planned interim analysis of an ongoing open-label randomised clinical trial in healthy adult volunteers aged 18-70 comparing 2 doses of a conjugate quadrivalent ACWY vaccine one month apart (Group 1) with one dose of a polysaccharide quadrivalent ACWY vaccine (ACWYVax®) followed by one dose of a conjugate quadrivalent ACWY vaccine one month later (Group 2). Methods & Results Sixty participants were immunised with two doses of vaccine at days 0 and 28. Meningococcal polysaccharide-specific memory B cells were enumerated in peripheral blood at days 0, 28 and 56 by cultured EliSpot assay. Median memory cell numbers were similar at baseline in the two groups (medians of 0.5-2.5 cells per million cultured lymphocytes). By both 28 and 56 days median memory cell numbers were higher in Group 1 than in Group 2 (5.3, 8.5 2.5 and 2.8 per million cultured lymphocytes for serogroups A, C, W135 & Y respectively vs. 2.0, 2.5, 1.0 and 0.75 at day 56). 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 (follicular B cells to conjugate vaccine in Group 1 mediating a T dependent response, compared to T independent responses to polysaccharide antigens in Group 2, mediated by B1 or marginal zone B cells ) Notably, the serogroup A component of the vaccines behaves in the same way as other polysaccharides despite data indicating that it may act as a T-dependent antigen.