IVI-NICED study, published in The Lancet, lays foundation for newly licensed vaccine’s global use

A health worker checks a vial of the oral cholera vaccine developed
by the IVI during a large-scale field trial in Kolkata, India, as vaccinees
and health officials look on.

A new low-cost killed whole-cell (WC) oral cholera vaccine was found to be protective against clinically significant cholera in an endemic setting in a large-scale field trial conducted among nearly 70,000 residents of Kolkata, India. The new vaccine was found to be safe and effective in young children, as well as older persons.  The IVI developed the vaccine by modifying an inexpensive vaccine produced in Vietnam. The new vaccine was licensed early this year in India.

The study findings are discussed in an article that appeared online in The Lancet (www.thelancet.com) on October 9th. This major study was conducted by the IVI in collaboration with the National Institute of Cholera and Enteric Diseases (NICED).

Killed WC oral cholera vaccines have been available for many years but they have not been used widely in developing countries with endemic cholera despite World Health Organization (WHO) recommendations for their use. Currently, Vietnam is the only cholera-endemic country that deploys a locally produced, killed WC oral cholera vaccines in high-risk areas.  However, the Vietnamese vaccine has not been approved for use worldwide because Vietnam’s  manufacturing process does not conform to WHO standards, and Vietnam’s national regulatory authority is not approved by the WHO.

To facilitate worldwide use of this vaccine, IVI scientists worked with the Vietnamese producer, VaBiotech, to modify the vaccine’s strain composition and dose, and to improve the manufacturing process to comply with WHO standards. The scientists found the modified vaccine to be safe and immunogenic among vaccine recipients in studies in Vietnam and India.

Subsequently, the IVI and NICED conducted a large-scale, double-blind efficacy trial that included nearly 70,000 residents of Kolkata aged one year and older. The residents received two doses of either the new cholera vaccine or a placebo. An interim analysis was performed after two years of follow-up post-vaccination.

IVI Director-General Dr. John Clemens said, “This interim analysis shows that the modified killed WC oral cholera vaccine is safe and efficacious, providing nearly 70 percent protection against clinically significant cholera for at least two years after vaccination.” The vaccine protected all age groups among individuals aged one year and older, and was not associated with side effects.

“The vaccine tested in this trial has several features suited to the control of cholera in developing countries,” Dr. Clemens said. “It is safe and protective against the current pandemic biotype (read a related story) of cholera (El Tor) in all age groups, including young children, who are at especially high risk of cholera in endemic settings.” An internationally licensed killed WC-based oral vaccine containing the recombinant cholera toxin B subunit (rBS-WC) is currently available.  Due to the high cost and requirement of buffer for administration of rBS-WC, it has not been taken up for use in developing countries. In contrast, the new IVI vaccine does not require any buffer, making it easier to administer, and is cheaper to produce, making mass vaccination campaigns more feasible.

In order for the new vaccine to be purchased by United Nations organizations such as UNICEF, the IVI transferred its production technology to the vaccine manufacturer, Shantha Biotechnics, in India, where the national regulatory authority is approved by the WHO. Shantha obtained licensure for this vaccine (Shanchol) on February 24, 2009 from the Indian national regulatory authority (read a related story), paving the way for the expanded use of the vaccine.

In a Lancet commentary about the Indian vaccine, Prof. Saranya Sridhar of the School of Public Health, University of California, Berkeley stated, “The story of the development of this vaccine underlines the success of an international collaborative effort of public–private partnership and academic research organizations when provided with adequate funding, infrastructure, and support. This success story ought to be an example for other vaccine initiatives, especially against malaria and HIV, to similarly engage industry and academia towards solving an urgent public health need.”

The IVI-NICED study is part of the IVI’s Cholera Vaccine Initiative (CHOVI), a research program supported by the Bill & Melinda Gates Foundation and the governments of Korea, Sweden, and Kuwait. The program aims to accelerate the introduction of oral cholera vaccines into public health programs of cholera-endemic countries.