Streptococcus agalactiae, or Group B Streptococcus (GBS), is one of the leading causes of neonatal sepsis, meningitis and pneumonia. Naturally occurring in the intestinal and vaginal tracts of approximately 30% of healthy women, this bacterium can be vertically transmitted to neonates during birth. Many studies have examined neonatal infection; however maternal research is lacking. This study utilised the murine model of GBS colonisation to examine the immune response against the five most common serotypes (Ia, Ib, II, III and V) associated with maternal colonisation and neonatal infection. We examined the differential immune responses between mice that remained colonised and mice that cleared infection over a 30 day period to determine if there was a signature immune profile associated with GBS clearance. Vaginal lavage of mice that cleared serotypes Ia, II and III had sustained reduced levels of TNFα, IL1β, IL10 and IL17. Enumeration of inflammatory infiltrate into the lumen of the vagina also revealed differential responses between the serotypes of GBS. T cell stimulation analysis at 30 days post infection indicated a degree of cross-serotype proliferation of CD4⁺ T cells. This study demonstrates that there is a signature immune response in mice that clear GBS infection and that colonisation with one serotype of GBS can lead to cross-serotype CD4⁺ T cell responses. These results could be used to develop non-antibiotic treatments to reduce vaginal colonisation, or perhaps predict those most likely to clear GBS colonisation during pregnancy. The cross-serotype T cell response provides promise that a vaccine to protect against all serotypes of GBS can be developed with further investigation into the exact antigens eliciting these responses.