Researchers in India have reported1 the development of a new live oral cholera vaccine that promises better protection than the currently available killed (or inactivated) vaccines.

"Our 100% India-made, India-designed vaccine gives 66% sero-conversion after a single dose as opposed to 53% by the existing vaccine after two doses," Amit Ghosh, currently Emeritus Scientist at the National Institute of Cholera and Enteric Diseases (NICED) in Kolkata, told Nature India.

Symptoms of cholera are primarily due to a toxin, cholera toxin (CT). The disease is transmitted by faecal-oral route through contaminated food and water. Cholera is now endemic in more than 50 countries and according to the World Health Organization (WHO), every year cholera affects around 3 to 3.5 million people globally, killing between 100,000 to 120,000.

Presently two killed whole-cell vaccines, given orally, are licensed by the WHO. Killed or inactivated vaccines are made from microorganisms that have been killed through physical or chemical processes. The Swedish recombinant B-subunit vaccine 'Dukoral', licensed since 1991, is expensive. The other oral killed vaccine 'Shanchol', marketed by Hyderabad-based Shantha Biotechnics, is a modified form of 'mORC-Vax' developed by a Vietnam-based company using technology transferred by Sweden. These vaccines require two doses for protection. The only licensed oral and live attenuated single-dose vaccine CVD 103-HgR that was used in Indonesia in the 1990s is no longer produced.

"Killed oral vaccines constitute major advances in cholera vaccine development but they need to be administered in two doses," Ghosh said. "With our vaccine it appears, a single dose would be enough." The vaccine was developed by Institute of Microbial Technology (IMTECH) in Chandigarh in collaboration with NICED and the Indian Institute of Chemical Biology (IICB), Kolkata, with funds from India's Department of Biotechnology (DBT). Ghosh, formerly the director of IMTECH, and colleagues in his IMTECH lab developed the vaccine along with Balakrish Nair and Thandavarayan Ramamurthy of NICED and Ranajit Kumar Ghosh of IICB.

Ghosh said the Indian-made live oral vaccine VA 1.4 was developed from a clinical isolate of 'Vibrio cholerae O1 El Tor' strain naturally devoid of the cholera toxin. The vaccine was made after a series of manipulations to introduce into the strain the gene responsible for production of the ‘B’ subunit of the cholera toxin. Tested in rabbits, the vaccine was found to provide full protection against cholera pathogens, Ghosh said.

The vaccine was evaluated in a double-blind trial in men and women aged 18–60 years in Kolkata. The vaccine did not elicit any serious adverse effect and sero-converted 65.9% of participants in the vaccinated group after just one dose. In contrast, a 2008 study2 in the same population using the 2-dose killed oral cholera vaccine showed a sero-conversion rate of only 53%.