Refined live attenuated Salmonella enterica serovar Typhimurium and Enteritidis vaccines mediate homologous and heterologous serogroup protection in mice.
Invasive nontyphoidal Salmonella (NTS) infections constitute a major health problem among infants and toddlers in sub-Saharan Africa; these infections also occur in infants and the elderly in developed countries. We genetically engineered a Salmonella enterica serovar Typhimurium strain of multilocus sequence type 313, the predominant genotype circulating in sub-Saharan Africa. We evaluated the capacities of S. Typhimurium and Salmonella enterica serovar Enteritidis ΔguaBA ΔclpX live oral vaccines to protect mice against a highly lethal challenge dose of the homologous serovar and determined protection against other group B and D serovars circulating in sub-Saharan Africa. The vaccines S. Typhimurium CVD 1931 and S. Enteritidis CVD 1944 were immunogenic and protected BALB/c mice against 10,000 50% lethal doses (LD50) of S. Typhimurium or S. Enteritidis, respectively. S. Typhimurium CVD 1931 protected mice against the group B serovar Salmonella enterica serovar Stanleyville (91% vaccine efficacy), and S. Enteritidis CVD 1944 protected mice against the group D serovar Salmonella enterica serovar Dublin (85% vaccine efficacy). High rates of survival were observed when mice were infected 12 weeks postimmunization, indicating that the vaccines elicited long-lived protective immunity. Whereas CVD 1931 did not protect against S. Enteritidis R11, CVD 1944 did mediate protection against S. Typhimurium D65 (81% efficacy). These findings suggest that a bivalent (S. Typhimurium and S. Enteritidis) vaccine would provide broad protection against the majority of invasive NTS infections in sub-Saharan Africa.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA stennant@medicine.umaryland.edu.
Sharon M
SM
Tennant
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Patrick
P
Schmidlein
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Raphael
R
Simon
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Marcela F
MF
Pasetti
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
James E
JE
Galen
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Myron M
MM
Levine
D000284:Administration, Oral; D017954:Africa South of the Sahara; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000276:immunology*; D056738:Cross Protection; D005260:Female; D005838:Genotype; D006801:Humans; D007928:Lethal Dose 50; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D022562:Salmonella Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012477:Salmonella enteritidis / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D012703:Serotyping; D016019:Survival Analysis; D014611:Vaccination; D014613:Vaccines, Attenuated
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022562:Salmonella Vaccines; D014613:Vaccines, Attenuated