Abstract: Using a lactoferrin latex agglutination assay, we have compared the inflammatory responses to a cholera vaccine candidate, CVD 110, in which all known toxin genes have been deleted or mutated yet still produced significant diarrhea, with a less reactive vaccine strain and wild-type El Tor and 0139 Vibrio cholerae strains. Data suggest that diarrhea due to attenuated and wild-type El Tor V. cholerae, and to a lesser extent 0139 V. cholerae, involves an inflammatory response. Further study is required to further elucidate the mechanism of the process(es) involved.

Abstract: Healthy adults (n=330) were randomized to receive either a bivalent vaccine composed of Vibrio cholerae CVD 103-HgR and Salmonella typhi Ty21a or a placebo. The combined vaccine was well tolerated. Approximately 80% of vaccines manifested a significant rise in anti-S. typhi immunoglobulin G or immunoglobulin A lipopolysaccharide antibody levels. Significant (fourfold or greater) rises in anti-Inaba or anti-Ogawa vibriocidal antibody titer were achieved by 94 and 80% of vaccine recipients, respectively. Elevated baseline vibriocidal antibody titers showed a modest suppressive effect on the rate of seroconversion.

Abstract: Many cholera bacteria are perfectly benign, but some strains have become deadly pathogens by acquiring packages of genes from elsewhere in their environment. New research on page 1910. reveals an agent that may be responsible for this Jekyll-to-Hyde transformation: a bacteriophage, a virus that infects the cholera bacterium itself. This phage carries the genes that encode the toxin that causes the disease9s life-threatening diarrhea. The new discovery raises questions about the development of live cholera vaccines and suggests a transfer mechanism for other bacterial virulence genes.

Abstract: Background: Immune protection against cholera infection is probably mediated in part by locally produced, intestinal secretory IgA (sIgA) antibodies. We study the kinetics of intestinal (sIgA) and systemic (serum IgG) antitoxin antibody responses after immunization with whole-cell/recombinant B subunit oral cholera vaccine (WC/rBS) in U.S. travelers to Mexico and Mexican volunteers. Methods: Two doses of WC/rBS were administered 10 days apart to ten U.S. adults, newly arrived in Mexico, and 18 Mexican nationals. Serum IgG and intestinal secretory IgA (sIgA) antibodies to the B subunit of cholera toxin were measured from day 0 to day 21 by a direct enzyme-linked immunosorbent assay (ELISA). Results: Positive serum IgG responses to vaccination were detected in 80% of U.S. adults and in 59% of Mexican adults. All volunteers, regardless of nationality, developed a positive sIgA antibody response to WC/rBS. No differences were observed between U.S. and Mexican volunteers in the magnitude and kinetics of serum IgG responses. We recorded differences in the kinetics of sIgA antibody, with early and late peak sIgA antitoxin responses demonstrated in the Mexican and U.S. volunteer groups, respectively. Although the presence or absence of antitoxin sIgA antibodies prevaccination (sIgA titer > 1:4) did not interfere with the final postimmunization magnitude of the antibody responses (sIgA measurements days 14 and 21), the initial measurement curves showed differences (sIgA measurements days 0 and 3). Conclusions: The WC/rBS vaccine stimulated antitoxin antibody formation both in serum and locally in the intestine. The presence or absence of specific sIgA antibodies prevaccination did not seem to interfere with the magnitude of the antibody responses postvaccination (days 14, 21). The measurement of sIgA responses in fecal extracts appears to provide a simple and sensitive method to assess the intestinal immune response to orally administered vaccines.

Abstract: In order to evaluate the safety and immunogenicity of domestic produced lyophilized recombinant, B-subunit, inactivated whole cell vaccine of vibrio cholerae (rBS-WC), 369 subjects were randomly divided into three groups and observed with masking method, one with high dose of vaccine (5 mg rBS and 10" WC), another with low dose (1 mg rBS and 10" WC), and the control one with placebo. Three doses of vaccine were given orally at an interval of seven days and 14 days, respectively. Results showed that only one subject had mild adverse reaction in the vaccine group (1/247) and none in the control group. Serum and fecal antibody conversion rates and average levels of antibodies in the two vaccine groups were significantly higher than those in control one. There was no significant difference in serum and fecal antibody conversion rate and average antibody levels between the two vaccine groups. But, antibody response was different among subjects of various sex, age, and vaccine doses. It indicates that rBS-WC vaccine of vibrio cholerae had good immunogenicity and safety.

Abstract: Cholera, which is one of the best-studied and understood of all infectious diseases from the purview of both clinical pathophysiology and molecular pathogenesis, commences with ingestion of a food or water vehicle containing pathogenic Vibrio cholerae O1 or O139. If the vibrios successfully transit the acid barrier of the stomach and pass through the pylorus, they may then initiate a series of adaptations that allow them to colonize the proximal small intestine, overcoming the peristaltic defence mechanism.

Abstract: First attempt at cholera vaccination was made by Jaime Ferran in 1884. Since then, a variety of strategies and methods have been evolved to create a safe, efficacious vaccine against cholera. For the first few years emphasis was on the development of parenteral vaccines. However, as a result of accumulation of a tremendous amount of knowledge, not only on Vibrio cholerae-the causative agent, but also on its interaction with the host, emphasis has shifted towards the development of oral vaccines. Two such vaccines, one killed, a whole cell/B subunit combination vaccine and the other a live attenuated one, have shown promise. The combination vaccine in its present state of development confers only a transient protection in young children, while the live attenuated one produces adverse reaction. To combat these, various strategies are being evolved. In one attempt, a potential candidate vaccine strain has been constructed from a non-reactogenic clinical isolate of V. cholerae, which is devoid of all known major virulence genes and is also a good colonizer. In animal studies this construct has shown considerable promise. This review discusses the various strategies that have been employed so far in the quest for an ideal cholera vaccine.

Abstract: The recent spread of cholera in the Americas and the emergence of Vibrio cholerae 0139 in Asia have stimulated researchers to design efficient vaccine formulations to combat increasing cholera morbidity and mortality Although the conventional heat-killed whole cell cholera vaccine continues to be offered during epidemics and in endemic foci, the novel whole cell killed plus recombinant cholera toxin B subunit vaccine and the live attenuated CVD 103-HgR vaccine are undergoing extensive field trials Preliminary trials with Bengal-15, a vaccine composed of live V cholerae 0139 without the toxin gene but containing recombinant B subunit, are promising

Abstract: Vaccination of female rabbits with cholera protective antigen (CPA) protected their F1 progeny from lethal challenge with Vibrio cholerae. Protection was determined by the choleragenic score and survival rates. Serum and milk IgG, IgM, IgA titres to CPA, cholera toxin, and LPS were determined. At 8 and 20 weeks post-immunization, mothers' milk, sera, and infants' sera showed elevated CPA-specific IgG and IgA, and infants were protected. Mothers' serum and milk antibody remained elevated for 36 weeks. At 26 weeks, mothers were re-bred, but their progeny were swapped and cross-fed. Infants born to the placebo-vaccinated mothers and nursed by CPA-immune nannies were partially protected from challenge. Infants born to CPA-immune mothers and cross-fed by the placebo-vaccinated nannies were less protected. CPA stimulated both transplacental and milk antibody, but passive immunity was primarily milk-derived. A 36-week booster vaccine stimulated an anamnestic serological response that did not provide protection equivalent to the original vaccine. CPA provided partial protective immunity to the milk-fed infant rabbits that suggests that CPA may be important in the development of a cholera vaccine.

Abstract: For most infectious diseases, elucidation of the mechanisms involved in either protection against subsequent clinical disease, or in the modification of the clinical outcome following infection, requires an understanding of the specific immune responses that follows infection. The application of this understanding is seen in the development of effective vaccines for prophylaxis, or in effective immunotherapeutic intervention. Historically, an understanding of ‘natural’ immunity has played, at best, only a limited role in the development of suitable vaccines. As a result, vaccines developed in the past have covered the range from being either highly effective, such as the inactivated or live attenuated poliovirus vaccine, or have been of practically no value at all, such as the inactivated parenterally administered cholera vaccine.

Abstract: This study addresses a mechanism for inducing systemic immunity to Shiga-like toxins by oral administration of a Shiga-like toxin I B-subunit-expressing Vibrio cholerae vaccine strain [CVD 103-HgR(pDA60)]. Two sets of three rabbits were given either CVD 103-HgR or CVD 103-HgR(pDA60) orally. All rabbits immunized with CVD 103-HgR(pDA60) developed neutralizing serum antibodies to Shiga-like toxin I. None of the controls developed such antibodies.