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Development and Testing of an Oral B Subunit-Whole Cell Cholera Vaccine Protecting Against Both O1 and O139 Cholera

Objective



The objective of the proposed research is to facilitate the development of a new oral cholera vaccine that would effectively and without any adverse reactions give high and sustained levels of immune protection against cholera caused by both Vibrio cholerae of the common 01 El Tor type and of the rapidly emerging, novel 0139 serotype.

There is an urgent need for an effective cholera vaccine.
Parenteral whole-cell vaccines against cholera have existed for almost a century, but these vaccines are no longer considered useful from a public health standpoint, mainly because of the short duration of protection they provide.
Intense research efforts in the 1980ies have now provided much improved oral cholera vaccines based on either a combination of killed cholera bacteria and purified B-subunit antigen, or on live attenuated mutants of V.cholerae 01.
In particular, the oral B subunit-whole cell (B-WC) cholera
vaccine developed in Sweden has been extensively tested and shown to give much better and more long-lasting immunity than seen with previous parenteral cholera vaccines, and this is now an approved licensed vaccine in Sweden.

The most advanced of the live attenuated cholera vaccine candidates, CVDl03-HgR developed in USA, has also given promising results when tested in volunteers.
However, neither of these vaccines are likely to give more than partial (the B-Ol WC vaccine) or nil (the CVD103-HgR vaccine) protection against cholera due to an emerging, rapidly spreading new serotype (0139) of V. chlolerae which is now threatening to cause a new, the 8th, cholera pandemic coinciding with the still continuing 7th pandemic.
Based on recent work on the new 0139 V. cholerae serotype organism researchers at the University of Goteborg, Sweden in collaboration with SBL Vaccine, Stockholm, are currently formulating a "new" bivalent oral B subunit - 01/0139 whole cell (WC) cholera vaccine with promising potential to give protection against both 01 and 0139 cholera.

The vaccine is the same as the previous B-01 WC except for now also comprising 5x101ø heat- or formalin-killed 0139 bacteria of a strain selected to stably express high levels of 0139 LPS and MSHA surface antigens.
Therefor, it is here proposed (1) to test the safety and intestinal mucosal IgA immunogenicity of this new, bivalent B-01/0139 WC vaccine in comparison with the licensed B-01 WC vaccine in phase 1 and phase 2 studies in volunteers in preparation for a possible field trial with the new vaccine; and (2) to undertake additional basic research to further define (in animals) the possible role of capsular antigen in immunity and vaccine development against cholera due to V.
cholerae 0139 as well as the mucosal immunogenic potential of subunit conjugate vaccine formulations between cholera B subunit and 0139 and 01 LPS and 0139 capsular antigens.

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

University of Göteborg
Address
10,Guldhedsgatan
413 46 Gfteborg
Sweden

Participants (4)

Institut National de la Santé et de la Recherche Médicale (INSERM)
France
Address
5 Place D'arsonval
69437 Lyon
International Centre for Diarrhoeal Disease Research
Bangladesh
Address

1000 Dhaka
Ludwig-Maximilians-Universität München
Germany
Address
Leopoldstraße 5
80802 München
National Public Health Institute
Finland
Address
166,Mannerheimintie
00300 Helsinki