Historical review of clinical vaccine studies at Oswaldo Cruz Institute and Oswaldo Cruz Foundation--technological development issues.

This paper presents, from the perspective of technological development and production, the results of an investigation examining 61 clinical studies with vaccines conducted in Brazil between 1938-2013, with the participation of the Oswaldo Cruz Institute (IOC) and the Oswaldo Cruz Foundation (Fiocruz). These studies have been identified and reviewed according to criteria, such as the kind of vaccine (viral, bacterial, parasitic), their rationale, design and methodological strategies. The results indicate that IOC and Fiocruz have accumulated along this time significant knowledge and experience for the performance of studies in all clinical phases and are prepared for the development of new vaccines products and processes. We recommend national policy strategies to overcome existing regulatory and financing constraints.

Babesiosis Vaccines: Lessons Learned, Challenges Ahead, and Future Glimpses.

The incidence and prevalence of babesiosis in animals and humans is increasing, yet prevention, control, or treatment measures remain limited and ineffective. Despite a growing body of new knowledge of the biology, pathogenicity, and virulence of Babesia parasites, there is still no well-defined, adequately effective and easily deployable vaccine. While numerous published studies suggest that the development of such anti-Babesia vaccines should be feasible, many others identify significant challenges that need to be overcome in order to succeed. Here, we review historic and recent attempts in babesiosis vaccine discovery to avoid past pitfalls, learn new lessons, and provide a roadmap to guide the development of next-generation babesiosis vaccines.

Development of effective living vaccines against bovine babesiosis--the longest field trial?

Between 1959 and 1996, research was performed to change a vaccine against babesiosis in Australia and to improve it as actual or threatened untoward field responses became apparent. The most significant change occurred in 1964 with the traditionally used carriers of Babesia being replaced as vaccine donors by acutely infected splenectomised calves. This ensured the infectivity of the vaccine and was fortuitously associated with a reduction in the virulence of Babesia bovis in vaccine. Since then, more than 27 million doses of highly infective vaccine have been supplied from the laboratory at Wacol near Brisbane. This vaccine reduced serious losses from babesiosis in vaccinated cattle in Australia to very low levels and has now gained acceptance worldwide. Research to ensure the continuing effectiveness of the vaccine has proved to be essential.

Fifty years of anticoccidial vaccines for poultry (1952-2002).

Although earlier investigators experimented with anticoccidial vaccines, the world's first commercially successful product was developed by Prof S. A. Edgar of Auburn University, Auburn, AL. This product contained live, nonattenuated Eimeria tenella oocysts and was first marketed by Dorn and Mitchell, Inc., in 1952. Under the trade names of DM Cecal Coccidiosis Vaccine, Coxine, NObiCOX, and CocciVac, it went through several formulations containing various Eimeria species that parasitize chickens, and a further product containing turkey Eimeria species was also developed. After many product and company changes, one turkey and two chicken formulations of CocciVac are still marketed worldwide by Schering-Plough Animal Health, Inc. Chicken and turkey formulations of Immucox, a similar type of vaccine, were developed by Dr. E.-H. Lee and first marketed in 1985 in Canada by Vetech Laboratories, Inc. In 1974, Dr. T. K. Jeffers of Hess and Clark, Inc., Ashland, OH, published his discovery of precocious lines of coccidia, which facilitated the development of the first attenuated anticoccidial vaccine. For commercial reasons, Jeffers was unable to do this himself, but this first attenuated vaccine was designed by Dr. M. W. Shirley and colleagues at the Houghton Poultry Research Station (HPRS) in the United Kingdom. The vaccine was commercially developed under license in the United Kingdom by Glaxo Animal Health Ltd. and then Pitman-Moore, Inc., and launched in The Netherlands during 1989 under the trade name Paracox. After further changes in company ownership, two formulations for chickens are now marketed worldwide by Schering-Plough Animal Health, Inc. Attenuation of coccidia by embryo adaptation was reported in 1972 in the United Kingdom by Dr. P. L. Long, who originally worked at the HPRS and later became a professor at the University of Georgia, Athens, GA. An embryo-adapted line of E. tenella was included with precocious lines of other species in a series of three attenuated vaccines for chickens under the trade name Livacox, developed by Dr. P. Bedrník and launched in the Czech Republic in 1992 by Biopharm. The formulations of all other commercially available live anticoccidial vaccines for poultry are currently based upon the scientific principles established for the CocciVac, Paracox or Livacox vaccines.

Immune responses and protection induced in mice by an industrialized vaccine against American cutaneous leishmaniasis.

An industrialized vaccine against American cutaneous leishmaniasis was compared to a laboratory made vaccine in its ability to induce cellular and humoral immune responses in mice. No differences were observed between seric IgG levels or lymphoblastic proliferation response of mice immunized with either vaccine. Antigenic composition, evaluated by SDS-PAGE, was identical in both preparations. Protection induced in mice against a challenge with infective parasites was also compared. The level of protection obtained with the industrialized vaccine was comparable to that induced by the laboratory made preparation. The results showed that the industrialization process did not alter the efficacy of the vaccine.

Leishmaniasis: current status of vaccine development.

Leishmaniae are obligatory intracellular protozoa in mononuclear phagocytes. They cause a spectrum of diseases, ranging in severity from spontaneously healing skin lesions to fatal visceral disease. Worldwide, there are 2 million new cases each year and 1/10 of the world's population is at risk of infection. To date, there are no vaccines against leishmaniasis and control measures rely on chemotherapy to alleviate disease and on vector control to reduce transmission. However, a major vaccine development program aimed initially at cutaneous leishmaniasis is under way. Studies in animal models and humans are evaluating the potential of genetically modified live attenuated vaccines, as well as a variety of recombinant antigens or the DNA encoding them. The program also focuses on new adjuvants, including cytokines, and delivery systems to target the T helper type 1 immune responses required for the elimination of this intracellular organism. The availability, in the near future, of the DNA sequences of the human and Leishmania genomes will extend the vaccine program. New vaccine candidates such as parasite virulence factors will be identified. Host susceptibility genes will be mapped to allow the vaccine to be targeted to the population most in need of protection.