Simulating Immune Interference on the Effect of a Bivalent Glycoconjugate Vaccine against Haemophilus influenzae Serotypes "a" and "b".

Objective. We sought to evaluate the immune responses to a bivalent Haemophilus influenzae glycoconjugate vaccine against serotypes "a" (Hia) and "b" (Hib) in the presence of the preexisting immunity to Hib. Methods. We developed a stochastic simulation model of humoral immune response to investigate the antigenic challenge of a bivalent combined glycoconjugate vaccine and a bivalent unimolecular glycoconjugate vaccine. We compared simulation outcomes in the absence of any preexisting immunity with an already primed immune response having specific memory B cells and/or anti-Hib antibodies. Results. The simulation results show that the preexisting immune responses to Hib or carrier protein (CP) may significantly impede the production of anti-Hia antibodies by a unimolecular vaccine. In contrast, the production of anti-Hia antibodies using a combined vaccine is inhibited only in the presence of CP immune responses. Conclusions. Preexisting immunity to Hib and CP may play a critical role in the development of immune responses against Hia or Hib using bivalent combined and unimolecular vaccine formulations. Our results suggest that a bivalent combined glycoconjugate vaccine with a carrier protein not previously used in Hib conjugate vaccines may be an effective formulation for generating immune responses to protect against both Hib and Hia infections.