Shigella flexneri 2a and sonnei I vaccine with two attenuating markers: construction, tolerability and immunogenicity in 143 children aged 3-17 years.
The vaccine candidates were constructed through stepwise incorporation of weakly attenuated purine auxotrophy with subsequent rifampicin resistance (RNA polymerase) mutation to yield optimal attenuation. These strains showed a maintained invasiveness for conjunctival epithelia. Therefore, while not causing keratoconjunctivitis, they were excreted for a short but marked period and provided partial protection in the Sereny test. Children tolerated the maximum dose of 1-3 x 10(9) colony-forming units (c.f.u.) of lyophilized vaccine without side effects. This total dose distributed among three oral inoculations, induced coproantibodies in 70% of recipients during the first three months. However, the single application of this total dose for primary immunization or booster proved to be more efficient: 90% of the subjects had markedly elevated titres for not less than six months.
Linde
K
K
Leipzig University, Germany.
Randhagen
B
B
Beer
J
J
Dentchev
V
V
Marinova
S
S
Vassilev
T
T
Bratoyeva
M
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D003228:Conjunctiva / Q000382:microbiology; D005243:Feces; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008297:Male; D012449:Safety; D012763:Shigella flexneri / Q000276:immunology*; D012764:Shigella sonnei / Q000276:immunology*; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated