Marcela F Pasetti

Publication Detail

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Safety and immune responses to attenuated Salmonella enterica serovar typhi oral live vector vaccines expressing tetanus toxin fragment C.

C O Tacket; J Galen; M B Sztein; G Losonsky; T L Wyant; J Nataro; S S Wasserman; R Edelman; S Chatfield; G Dougan; et al. (Profiled Authors: James E Galen; Myron M Levine; Marcelo B Sztein)

Center for Vaccine Development, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, Maryland 21201, USA. ctacket@medicine.umaryland.edu
Clinical immunology (Orlando, Fla.) 2000;97(2):146-53.

Attenuated Salmonella enterica serovar Typhi vaccine strain CVD 908-htrA was used as a vector to deliver fragment C of tetanus toxin as a single-dose oral tetanus vaccine candidate to elicit protective levels of serum tetanus antitoxin. Twenty-one healthy adult volunteers received doses of 1.6 x 10(7) to 8.2 x 10(9) CFU of one of two strains, CVD 908-htrA(pTETnir15) or CVD 908-htrA(pTETlpp), which contained plasmid-encoded fragment C, with sodium bicarbonate, and the safety and immune responses to serovar Typhi antigens and tetanus toxin were assessed. No volunteer had fever or positive blood cultures after vaccination, although diarrhea occurred in 3 volunteers and vomiting in 2 volunteers within 3 weeks after vaccination. Most volunteers excreted the vaccine strain in the first 72 h after vaccination. Three of nine volunteers who received 10(8) CFU or higher doses of the CVD 908-htrA(pTETlpp) construct developed rises in serum antitoxin antibodies. The serum and cellular immune responses to serovar Typhi antigens were less frequent than those previously observed in volunteers who ingested the parent strain CVD 908-htrA. This study demonstrates that fragment C of tetanus toxin delivered orally to volunteers in an S. Typhi vector can elicit protective levels of serum antitoxin.

4 Originating Grant

• 1.

  Levine, Myron Max

  BACTERIAL LIVE VECTOR-BASED VACCINE AGAINST MALARIA

  1 April 1997 - 31 May 2006

  NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

• 2.

  SZTEIN, MARCELO B.

  Immune Mechanisms of Protection in S Typhi Vaccines

  1 September 1994 - 30 November 2011

  NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

• 3.

  Levine, Myron Max

  Recombinant & live oral Salmonella typhi hybrid vaccines

  1 April 1990 - 28 February 2009

  NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

• 4.

  LEVINE, MYRON M

  RECOMBINANT & LIVE ORAL SALMONELLA TYPHI HYBRID VACCINES

Scientific Context

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