Abstract. While new, higher-valency pneumococcal conjugate vaccines( PCVs), PCV15 and PCV20, will include important serotypes, their impact and cost-effectiveness will likely be less than what was achieved with introduction of PCV7, PCV10 and PCV13 because, in recent years, prevalent serotypes causing infections have changed and continue to change. Here we propose a clinical study, vaccinating children with a low cost-to-produce, serotype-independent, killed, non-capsulated avirulent whole-cell Streptococcus pneumoniae (wSp) vaccine that elicits Th17 cell-mediated immunity and antibodies against all pneumococcal serotyypes, and which has been tested in adults and toddlers. Nasopharyngeal (NP) colonization is a prerequisite to pneumococcal diseases and transmission. We will evaluate the efficacy of wSp vaccination in young children on pneumococcal NP colonization at times of health and onset of acute otitis media. Notably, prevention of pneumococcal NP colonization may be a surrogate for prevention by wSp of pneumococcal infections. In addition, we will confirm the safety and immunogenicity of wSp. Demonstration of a reduction of NP colonization, safety, immunogenicity of wSp would engage the scientific and public health community and commercialization support for additional licensure studies to next test for protection against various pneumococcal diseases, to determine whether wSp could complement PCVs or even replace PCVs as an inexpensive, serotype-independent vaccine.