Animal study for residual virulence, immunogenicity and protective effect of alive bivalent Shigella vaccine candidate strain DOM3
Objective To develop a 
polyvalent, safe, highly effective and non antibiotic resistance vaccine. Methods Animal 
model was used to evaluate the residual virulence, immunogenicity and protective effect of a 
live bivalent Shigella vaccine candidate strain DOM3(expressing S.flexneri 2a and 
S.dysenteriae Ⅰ somatic antigen) constructed by balanced plasmid chromosome lethal gene 
expressing system based on thyA gene. Results The virulence of DOM3 was 120 and 57 times 
respectively less than that of the wild type strains S.flexneri 2a 301 and S.dysenteriae Ⅰ 
112 in Kunming mice, 875 and 195 times respectively less than that of wild type strains 
S.flexneri 2a 301 and S.dysenteriae Ⅰ112 in SPF BALB/c mice. DOM3 had the similar 
immunogenicity to S.flexneri 2a 301, but weaker immunogenicity than S.dysenteriae Ⅰ 
112. The peak of serum IgA and IgG of immunized mice appeared in the second week after the 
last injection, but IgM in the first week. Antibody titers were likely to be stable after 6 weeks. 
Anti S.flexneri 2a and anti S.dysenteriae Ⅰantibodies appeared with similar trendency. 
The mice subcutaneously inoculated with DOM3 could be protected from the challenge of 30 LD 
50 (6.13×10 7 CFU) wild type strain S. flexneri 2a 301 and 21 LD 50 (6.26×10 7 CFU) 
wild type strain S.dysenteriae Ⅰ112 respectively in Kunming mice, and 20 LD 50 (1.38× 
10 6 CFU) wild type strain S.flexneri 2a 301 and 23 LD 50 (6.95×10 6 CFU) wild type 
strain S.dysenteriae Ⅰ112 in SPF BALB/c mice, through intraperitoneal injection, the 
protective rate was 90% and 70% respectively in Kunming mice, and 100% and 80% 
respectively to SPF BALB/c mice. Conclusions DOM3 may be a promising Shigella vaccine 
candidate strain. Volunteer study on safety, immunogenicity should be done based on the 
results above.