Serum IgG antibodies to Shigella lipopolysaccharide antigens–a correlate of protection against shigellosis

Abstract

Shigella is a leading cause of diarrhea among children globally and of diarrheal deaths among children under 5 years of age in low- and middle-income countries. To date, no licensed Shigella vaccine exists. We review evidence that serum IgG antibodies to Shigella LPS represent a good correlate of protection against shigellosis; this could support the process of development and evaluation of Shigella vaccine candidates. Case-control and cohort studies conducted among Israeli soldiers serving under field conditions showed significant serotype-specific inverse associations between pre-exposure serum IgG antibodies to Shigella LPS and shigellosis incidence. The same serum IgG fraction showed a dose–response relationship with the protective efficacy attained by vaccine candidates tested in phase III trials of young adults and children aged 1–4 years and in Controlled Human Infection Model studies and exhibited mechanistic protective capabilities. Identifying a threshold level of these antibodies associated with protection can promote the development of an efficacious vaccine for infants and young children.