Live Shigella flexneri 2a and Shigella sonnei I vaccine candidate strains with two attenuating markers. I. Construction of vaccine candidate strains with retained invasiveness but reduced intracellular multiplication.
Live Shigella flexneri 2a and Shigella sonnei Phase I vaccine candidate strains with two virulence-reducing markers were constructed through stepwise incorporation of weakly attenuating purine auxotrophy with subsequent rifampicin-resistance (RNA polymerase) mutation to yield optimal attenuation. These vaccine candidate strains showed an unaltered plasmid profile; did not cause keratoconjunctivitis in the Sereny test, while being excreted for a short but still marked period and providing partial protection from wild-strain infection; exhibited for guinea-pig conjunctival epithelia, HeLa cells and rat enterocytes a maintained invasiveness with reduced intracellular multiplication with little, if any, reversible cell damage; and produced, just as their ultrasonic lysates, no exudative reaction in the rabbit gut loop test.
Linde
K
K
Institute of Medical Microbiology and Epidemiology, Karl Marx University, Leipzig, GDR.
Dentchev
V
V
Bondarenko
V
V
Marinova
S
S
Randhagen
B
B
Bratoyeva
M
M
Tsvetanov
Y
Y
Romanova
Y
Y
D000818:Animals; D001428:Bacterial Vaccines; D003228:Conjunctiva / Q000382:microbiology; D005819:Genetic Markers; D006168:Guinea Pigs; D006367:HeLa Cells; D006801:Humans; D010957:Plasmids; D011817:Rabbits; D051381:Rats; D012763:Shigella flexneri / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D012764:Shigella sonnei / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014161:Transduction, Genetic; D014613:Vaccines, Attenuated; D014774:Virulence / Q000235:genetics
D001428:Bacterial Vaccines; D005819:Genetic Markers; D014613:Vaccines, Attenuated