The efforts were focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. We generated a stable Escherichia coli construct expressing functional recombinant PsaA and prepared CPS-rPsaA conjugate. The distribution of anti-CPS antibody response was almost completely of IgG2a subclass followed by IgG3 and low level of IgG1 subclass, which was opposite to the distribution of anti-PsaA IgG subclass antibodies. Though rPsaA was not detectable on the surface of the pneumococcal strain, the CPS-rPsaA conjugate possessed more accessibility to the surface of the strain. Mice immunized with conjugate exhibited rapid bacterial clearance from blood for the first 23h and afterward provided the best protection against challenge with pneumococcal 23F strain.