Public health authorities would like to have at their disposal a safe, practical, inexpensive, and highly effective vaccine to provide long-term protection against cholera. The Diarrheal Diseases Control Programme of the World Health Organization has targeted the development of an improved vaccine against cholera as a high priority.1 Such a vaccine to combat cholera is not yet in the public health armamentarium but, as shown in this chapter, several promising candidates are on the horizon.

Immunity and Vaccine Development

Introduction: Cholera remains a problem in developing countries and a risk for travelers. Hypochlorhydria, blood group O, cardiac and renal disease increase the risk of developing cholera gravis. O...

https://www.tandfonline.com/doi/pdf/10.1080/14760584.2017.1291348

PaxVax CVD 103-HgR single-dose live oral cholera vaccine.

Background: Injected cholera vaccines are rarely used today, although they may have some benefit. It is valuable to summarize the evidence for effectiveness of injected cholera vaccines for comparison with newer oral vaccines (subject of a separate Cochrane Review).

Objectives: To evaluate killed whole cell (KWC) cholera vaccines and other inactive subunit vaccines (administered by injection) for preventing cholera and death, and to evaluate the adverse effects.

Search methods: In September 2008, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2008, Issue 3), EMBASE, and LILACS. We also searched reference lists and handsearched the journal Vaccine up to 1997.

Selection criteria: Randomized and quasi-randomized controlled trials comparing injected cholera vaccines (KWC or other inactive subunit) with placebo, control vaccines, or no intervention in adults and children irrespective of immune status or special risk category.

Data collection and analysis: Two authors extracted data and assessed trial methodological quality independently. Dichotomous data were reported using the risk ratio (RR) with 95% confidence intervals (CI). Vaccine efficacies were also calculated (% vaccine efficacy = (1-RR) x 100%).

Main results: Sixteen trials, involving over one million adults, children and infants, fulfilled the inclusion criteria. Twenty-four comparisons reported on vaccine efficacy (cholera cases and/or deaths) and 11 comparisons considered adverse effects (nine reported on both). Compared to placebo, vaccinees had a reduced risk of death from cholera (RR 0.49, 95% CI 0.25 to 0.93; 837,442 participants) and a reduced risk of contracting cholera at 12 months (RR 0.52, 95% CI 0.42 to 0.65, random-effects model; 1,512,573 participants). This translates to an efficacy of 48%, 95% confidence interval 35% to 58%. Significant protection lasted for two years, even after only a single dose, and for three years with an annual booster. Children over five years and adults were protected for up to three years, while children under five years were protected for up to a year. Injected cholera vaccines were associated with more systemic and local adverse effects compared to placebo, but these were not severe or life-threatening.

Authors' conclusions: Injected cholera vaccines appear to be safe and relatively more effective than usually realized. Protection against cholera persists for up to two years following a single dose of vaccine, and for three years with an annual booster. However, they have been superseded by oral vaccines.

Vaccines for preventing cholera: killed whole cell or other subunit vaccines (injected).

Cholera remains an important public health problem in many parts of the world and the availability of an effective cholera vaccine is important for the prevention of cholera in the countries affected by this disease. Despite the apearance in 1992 of a new serogroup, O139, of Vibrio cholerae, most of the cholera outbreaks are still caused by V. cholerae O1 biotype El Tor. Vaccine trials in Asia from 1968 to 1971, and studies of the production of serotype-specific antiserum in rabbits and of the protective activity of monoclonal antibodies against diarrhoeal disease in neonatal mice, have led to the conclusion that the Ogawa serotype contains a specific antigenic determinant whereas the Inaba serotype contains a different antigenic determinant that cross-reacts with the Ogawa serotype. By studying the binding of anti-Ogawa monoclonal antibodies to synthetic oligosaccharide fragments mimicking the Ogawa O-specific polysaccharide, it has been shown that the terminal monosaccharide, bearing the 2-O-methyl group in the O-specific polysaccharide, is most probably the serotype-specific determinant for the Ogawa strain. However, study of the binding of a monoclonal antibody recognizing both Ogawa and Inaba serotypes suggested partial recognition of the core as well as of the O-specific polysaccharide of the LPS of V. cholerae O1. To further characterize this antigenic determinant that is common to the Ogawa and Inaba serotypes, the core and the O-specific polysaccharide linked to the core of V. cholerae O1 LPS were purified by preparative electrophoresis. The O-specific polysaccharide linked to the core was subjected to periodate oxidation to destroy sugars from the core. Binding studies of these purified saccharide fragments to a monoclonal antibody which is protective in mice and specific to the antigenic determinant common to Ogawa and Inaba serotypes showed that both the core and the O-specific polysaccharide are involved in this common antigenic determinant. This explains how the presence or the absence of the Ogawa-specific antigenic determinant would lead to the expression of two independent antigenic determinants of V. cholerae O1, one specific to the Ogawa serotype and the other common to both Ogawa and Inaba serotypes.

Immunochemical characterization of an Ogawa-Inaba common antigenic determinant of Vibrio cholerae O1.

Spatial and temporal comparison of selected cancers in dogs and humans, Michigan, USA, 1964-1994.

Part 1 of this Memorandum appeared in Vol. 49, pages 81-91. Part 2 covers neoplasia of the bovine urinary bladder; tumours of unknown cause (including melanomas, osteosarcomas, mammary tumours, lymphosarcomas, mastocytomas, transmissible venereal tumours, and histiocytomas); and the applications of animal models in studies of neoplasia. A summary of animal models is included as an annex.

Immunity to cancer. Naturally occurring tumours in domestic animals as models for research. Part 2

PREVENTIVE VACCINATION IS SUCCESSFULLY PRACTISED TODAY AGAINST TWO NEOPLASTIC DISEASES OF DOMESTIC ANIMALS: fibropapillomatosis of cattle and Marek's disease of chickens (a lymphoproliferative disease). Also it may soon be possible to immunize cats against lymphosarcoma. This memorandum describes these diseases and the immunological reactions involved. It also mentions a number of other tumours that could be used for immunological studies.The greatest advances in immunity have been made with the tumours caused by viruses. The killed papillomavirus vaccine used against bovine papillomatosis produces demonstrable antibodies against the virus. In the case of Marek's disease of chickens, which is due to a herpesvirus, a live virus vaccine is used. This does not prevent infection with virulent virus, but prevents the development of neoplasia. The mechanism by which the vaccine produces its effect is not yet known. Immunization with live and with killed vaccines has been successfully carried out experimentally against leukosis of chickens, which is caused by an oncornavirus. There is evidence that it will be possible to vaccinate cats against lymphosarcoma with non-living vaccine.Naturally occurring cancer in domestic animals parallels cancer in man more closely than does experimentally induced cancer in inbred laboratory animals; therefore immunological studies with the former are more likely to yield results relevant to the problem in man. Experimental cancer in rodents provides models that have the great advantages of uniformity and availability, and they cannot be replaced. However, models in domestic animals offer valuable supplementary systems for research aimed at elucidating the basic principles of immunity to cancer. (Less)

L N Owen

Papers

Immunity to cancer. Naturally occurring tumours in domestic animals as models for research. Part 2

Immunity to cancer. Naturally occurring tumours in domestic animals as models for research. Part 1