Head-to-Head Comparison of Humoral Immune Responses to Vi Capsular Polysaccharide and Salmonella Typhi Ty21a Typhoid Vaccines–A Randomized Trial

Anu Kantele,Jussi M Kantele,Riitta Karttunen,Sari H Pakkanen,Suzan Hm Rooijakkers

doi:10.1371/journal.pone.0060583

Anu Kantele, Jussi M Kantele + Show 3 more

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https://doi.org/10.1371/journal.pone.0060583

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Abstract

BackgroundThe two typhoid vaccines, the parenteral Vi capsular polysaccharide and the oral live whole-cell Salmonella Typhi Ty21a vaccine, provide similar levels of protection in field trials. Sharing no antigens, they are thought to confer protection by different mechanisms. This is the first head-to-head study to compare the humoral immune responses to these two vaccines.Methods50 age- and gender-matched volunteers were immunized, 25 with the Vi and 25 with the Ty21a vaccine. Circulating plasmablasts reactive with whole-cell Salmonella Typhi or one of the typhoidal antigenic structures, Vi, O-9,12, and H-d antigens, were identified as antibody-secreting cells (ASC) with ELISPOT. Homing receptor (HR) expressions were determined. These results were compared with ASC in four patients with typhoid fever. Antibodies to S. Typhi lipopolysaccharides were assessed in cultures of ALS (antibodies in lymphocyte supernatants) and in serum with ELISA.ResultsIn 49 out of 50 vaccinees, no typhoid-specific plasmablasts were seen before vaccination. On day 7, response to Vi antigen was mounted in 24/25 volunteers in the Vi, and none in the Ty21a group; response to S. Typhi and O-9,12 was mounted in 49/50 vaccinees; and to H-d in 3/50. The numbers of typhoid-specific plasmablasts (total of ASC to Vi, O-9,12 and H-d antigens) proved equal in the vaccination groups. The HR expressions indicated a mainly systemic homing in the Vi and intestinal in the Ty21a group, the latter resembling that in natural infection. Plasmablasts proved more sensitive than serum and ALS in assessing the immune response.ConclusionsThe typhoid-specific humoral responses to Vi and Ty21a vaccines are similar in magnitude, but differ in expected localization and antigen-specificity. The unforeseen O antigen-specific response in the Vi group is probably due to lipopolysaccharide contaminating the vaccine preparation. Only the response to Ty21a vaccine was found to imitate that in natural infection.Trial RegistrationCurrent Controlled Trials Ltd. c/o BioMed Central ISRCTN68125331

Highlights

Typhoid fever continues to comprise a significant health problem in developing countries, posing a risk for travellers as well [1,2]
Two vaccines are available for clinical use: the parenteral Vi capsular polysaccharide vaccine, and the oral live Salmonella Typhi Ty21a vaccine [1,2,3,4]
In addition to getting answers to our initial questions, we found that the antigenspecificities in the plasmablast responses did not differ as much as had been thought

Summary

Introduction

Typhoid fever continues to comprise a significant health problem in developing countries, posing a risk for travellers as well [1,2]. Two vaccines are available for clinical use: the parenteral Vi capsular polysaccharide vaccine, and the oral live Salmonella Typhi Ty21a vaccine [1,2,3,4] Both have proved immunogenic, providing similar levels of protection against typhoid fever in clinical trials [2,3,4], yet there are no head-to-head studies comparing their immunogenicity and protective efficacy. The two typhoid vaccines, the parenteral Vi capsular polysaccharide and the oral live whole-cell Salmonella Typhi Ty21a vaccine, provide similar levels of protection in field trials. Sharing no antigens, they are thought to confer protection by different mechanisms. This is the first head-to-head study to compare the humoral immune responses to these two vaccines

Methods

Results

Conclusion