Role of monoclonal O-antigen antibody epitope specificity and isotype in protection against experimental mouse typhoid

Phase 1 and Phase 2 Studies ofSalmonella entericaSerovar Paratyphi A O-Specific Polysaccharide-Tetanus Toxoid Conjugates in Adults, Teenagers, and 2- to 4-Year-Old Children in Vietnam

“…Subcutaneous injection of mice with S. enterica serovar Paratyphi A conjugates using only 1/10 of a human dose in saline elicited bactericidal antibodies specific for group A but not group B Salmonella (35). This is consistent with the immunodominant region of the group-specific antigen (factor 2), conferred by paratose, as predicted from the proposed structures of group A, B, and D O-SPs of salmonellae (8)(9)(10)17).…”

“…The O-SP of S. typhimurium (group B) is 2-O acetylated at abequose, conferring the specificity defined as factor 5 (8, 9). Carlin et al reported that a murine monoclonal IgA antibody to factor 5 had low protective activity against S. enterica serovar Typhimurium (10). It cannot be concluded that the O-acetyl does not have important biological activity for group B Salmonella because IgA may not protect against blood-borne infection.…”

“…The lipopolysaccharide (LPS) of nontyphoidal Salmonella is both an essential virulence factor and a protective antigen (50). Animal experiments on the structurally related serogroup B and clinical results with Vi capsular polysaccharide of S. enterica serovar Typhi were the basis for our prediction that a critical level of serum immunoglobulin G (IgG) to the O-specific polysaccharide (O-SP) will confer protection against S. enterica serovar Paratyphi A (10,15,16,50,58,64). Accordingly, we developed O-SP conjugates of S. enterica serovar Paratyphi A designed to elicit IgG LPS antibodies in serum (35).…”

Diverse virulence traits underlying different clinical outcomes of Salmonella infection

“…Although the relative importance of antibodies and T lymphocytes in suppressing Salmonella infections is controversial (12), there is ample evidence that antibodies protect both humans and mice against Salmonella (13,14). Furthermore, in most experimental systems, immunity to Salmonella is O antigen-specific (15,16). Thus, it might benefit the bacteria to change the structure of their LPS, which is indeed observed, although not during the course of a single infection.…”

Glycoconjugate vaccine strategies for protection against invasiveSalmonellainfections

“…49 A study to assess the protection related to specific epitopes within OPS suggests that antibodies to the immunodominant group-specific epitope constitute the primary protective species; IgG or IgM specific for epitope 4 protected to a greater extent than an IgG to epitope 12. 50 A monoclonal IgA directed against epitope 5 has also been shown to prevent mucosal infection with S. Typhimurium given to mice by oral challenge. 40,51 Polyclonal antibodies elicited by COPS conjugates in rabbits and mice also provide passive immunity against fatal NTS challenge in mice.…”