By David N. Leff

Vaccines in development against tropical diseases -- cholera for example -- usually carry price tags in the $20 to $30 range per immunization. And they must be kept refrigerated until used. Both restraints put them out of bounds for Third World populations at risk.

Now, Vietnamese vaccinologists report that they have successfully field-tested a killed, whole-cell cholera vaccine that costs $0.10 a dose, and requires no cold-chain storage.

Their account in the current issue of The Lancet, dated Jan. 25, 1997, bears the title: "Field trial of a locally produced, killed, oral cholera vaccine in Vietnam."

Cholera revisits parts of Vietnam regularly every three years. Between Aug. 20, 1993 and Oct. 4, 1993, a time-
limited outbreak of the infection put to the test an open trial of the local formulation, involving 134,453 inhabitants of the central coastal city of Hue. Eight to 10 months earlier, late in 1992, half of this population, 67,395 people, swallowed two doses, spaced two weeks apart, of the killed Vibro cholerae preventative.

The control cohort consisted of 67,058 individuals living in alternate houses in the districts of the city staked out for the immunization action. Vietnam's population is 74 million.

During that brief epidemic in 1993, 129 confirmed cases of cholera infection occurred among the Hue participants. Only one person died, an 80-year-old man from a no-vaccine household.

All told, 37 vaccinees, and 92 non-vaccinees, were hospitalized, reflecting an over-all efficacy of 66 percent. Interestingly, protection was slightly higher among vaccinated inhabitants of homes supplied with unclean water, than in households with clean water sources.

Harvard microbiologist Eric Rubin cites one possible explanation: "The kids with unclean water supplies," he told BioWorld Today, probably get a lot of other antigenic stimulations, which may be cross-protective to some extent. Or it might boost their secondary immune response to the vaccine."

Save-The-Children Vaccine Ingredient

Most significant, the authors of the Lancet paper point out, was that the 66 percent efficacy rate protected not only adults but children under the age of five. This critical age group had been left unprotected by a recent, large-scale field trial in Bangladesh of a killed, whole-cell Swedish cholera vaccine, which proved 50 percent effective in adults.

That Swedish formulation consisted of four different cholera biotypes of the worldwide El Tor serogroup of Vibrio cholerae. The Vietnamese workers replaced one of these target immunogens with a variant "known to express toxin-coregulated pili [tiny hair-like filaments] more efficiently," and other components. They attribute their vaccine's effectiveness against "cholera of life-threatening severity" among toddler-age vaccinees, at least in part, to this changeover. (See BioWorld Today, July 3, 1996, p. 1.)

"However, this explanation is unlikely," said veteran U.S. vaccinologist Myron Levine in a commentary accompanying the Lancet article. But he allowed that the "low cost, complete safety and apparent heat stability" of the Vietnamese product are advantages. Levine heads the Center for Vaccine Development at the University of Maryland School of Medicine, in Baltimore.

Besides Vietnamese scientists from the National Institute of Hygiene and Epidemiology in Hanoi, the Institute of Vaccines in Nha Trang and the Center for Preventive Medicine in Hue, the field trial's co-authors included John Clemens, chief of epidemiology at the U.S. National Institute of Child Health and Human Development in Bethesda, Md.

He described the study's departure from customary controls and protocols, but adduced its validity by applying strict statistical paradigms to minimize bias.

Its authors concede the trial's limitations as including:

* protection could be documented for only 10 months after vaccination;

* participants were chosen by alternate households, not true randomization;

* non-vaccinees did not get a placebo.

Rubin recalled that "Starting in India in 1993, there was an outbreak of a new and different cholera strain, named O139 Bengal, which basically came and wiped out the previous O1 strain on the Indian subcontinent." (See BioWorld Today, Sept. 6, 1994, p. 1.)

In parts of Southeast Asia," Rubin continued, "where O139 has spread, it is still very prevalent, and these Swedish and Vietnamese vaccines [limited to O1] are probably not protective against O139."

The Government of Vietnam has lately added O139 immunogens to its O1 vaccine cocktail, and plans a large-scale, double-blind field trial of this new, bivalent vaccine, starting in 1997. *