The 23-valent
polysaccharide vaccine and the 7-valent pneumococcal
conjugate vaccine are licensed
vaccines that protect against
pneumococcal infections worldwide. However, the incidence of
pneumococcal diseases remains high in low-income countries. Whole-cell
vaccines with high safety and strong immunogenicity may be a favorable choice. We previously obtained a
capsule-deficient Streptococcus pneumoniae mutant named SPY1 derived from strain D39. As an attenuated live
pneumococcal vaccine, intranasal immunization with SPY1 elicits broad serotype-independent protection against
pneumococcal infection. In this study, for safety consideration, we inactivated SPY1 with 70%
ethanol and intranasally immunized BALB/c mice with killed SPY1 plus
cholera toxin adjuvant for four times. Results showed that intranasal immunization with inactivated SPY1 induced strong humoral and cellular immune responses. Intranasal immunization with inactivated SPY1 plus
cholera toxin adjuvant elicited effective serotype-independent protection against the colonization of pneumococcal strains 19F and 4 as well as lethal
infection of pneumococcal serotypes 2, 3, 14, and 6B. The protection rates provided by inactivated SPY1 against lethal
pneumococcal infection were comparable to those of currently used
polysaccharide vaccines. In addition,
vaccine-specific B-cell and T-cell immune responses mediated the protection elicited by SPY1. In conclusion, the 70%
ethanol-inactivated pneumococcal whole-cell
vaccine SPY1 is a potentially safe and less complex
vaccine strategy that offers broad protection against S. pneumoniae.