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Infection and Immunity, March 2000, p. 1196-1201, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Phase 2 Clinical Trial of Attenuated Salmonella enterica Serovar Typhi Oral Live Vector Vaccine CVD 908-htrA in U.S. Volunteers

Carol O. Tacket,1,* Marcelo B. Sztein,1 Steven S. Wasserman,1 Genevieve Losonsky,1 Karen L. Kotloff,1 Timothy L. Wyant,1 James P. Nataro,1 Robert Edelman,1 Judith Perry,2 Philip Bedford,3 David Brown,4 Stephen Chatfield,5,dagger Gordon Dougan,6 and Myron M. Levine1

Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, Baltimore,1 and University of Maryland, College Park, University Health Center, College Park,2 Maryland; and Peptide Therapeutics Group plc, Cambridge,3 Evans Medical Limited, Liverpool,4 and Medeva Group Research5 and Imperial College of Science, Technology, and Medicine,6 London, England

Received 21 September 1999/Accepted 30 November 1999

Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens. We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA in a double-blind, placebo-controlled, crossover study. There were no differences in the rates of side effects among volunteers who received high-dose vaccine (4.5 × 108 CFU), lower-dose vaccine (5 × 107 CFU), or placebo in the 21 days after vaccination, although recipients of high-dose vaccine (8%) had more frequent diarrhea than placebo recipients (0%) in the first 7 days. Seventy-seven percent and 46% of recipients of high- and lower-dose vaccines, respectively, briefly excreted vaccine organisms in their stools. All blood cultures were negative. Antibody-secreting cells producing antilipopolysaccharide (LPS) immunoglobulin A (IgA) were detected in 100 and 92% of recipients of high- and lower-dose vaccines, respectively. Almost half the volunteers developed serum anti-LPS IgG. Lymphocyte proliferation and gamma interferon production against serovar Typhi antigens occurred in a significant proportion of vaccinees. This phase 2 study supports the further development of CVD 908-htrA as a single-dose vaccine against typhoid fever and as a possible live vector for oral delivery of other vaccine antigens.

* Corresponding author. Mailing address: Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, 685 West Baltimore St., Baltimore, MD 21201. Phone: (410) 706-5328. Fax: (410) 706-4171. E-mail: ctacket{at}medicine.umaryland.edu.

dagger Present address: Microscience Ltd., London, England.

Infection and Immunity, March 2000, p. 1196-1201, Vol. 68, No. 3
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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