Future vaccines and a global perspective

Advances in medical biotechnology mean that vaccines to prevent more than 75 infectious diseases are being or have been developed. Vaccination is unfortunately not reliant purely on biotechnology but also on politics and resources. Countries with the greatest demand for vaccines have the least ability to pay for or produce them. Health-care Infrastructure and diagnostic facilities also hamper immunisation projects in developing countries. Charitable organisations are relied on heavily to support such projects but the challenge to ensure all infants are immunised against the most common infections of childhood is still enormous. Difficulties that present themselves now should not prevent us looking into future possibilities such as immunisation during pregnancy and targeting of children for immunisation against sexually transmitted diseases. Other avenues for research are in administration of vaccines. A move to mucosal immunisation rather than use of the syringe and needle would be positive both economically and from the point of view of risk of needle contamination. Plant science may also provide a new vehicle for vaccines by engineering plants such as the banana tree to be naturally bioencapsulated vaccines. Prospects for control and eradication of infectious disease in the next century are certainly good.     

Polysaccharide vaccines. II. Meningococcal vaccines

A variety of indirect evidence suggests that mammary tumors can synthesize free estrogens in situ via the sulfatase enzyme. The present study utilized an isotopic kinetic technique to provide direct confirmation of local tumor synthesis. Animals bearing nitrosomethylurea (NMU)-induced rat mammary tumors were infused with 14C-estrone as well as 3H-estrone sulfate and plasma:tissue gradients for each steroid measured. Liver, serving as a control tissue, uniformly synthesized free estrone from estrone sulfate with local synthesis in this organ providing an average of 78 +/- 1.0% of the estrone in this tissue. In rat mammary tumors, five out of seven synthesized estrone locally with individual values ranging from 19 to 50% synthesized in tissue. These data indicate that liver uniformly converts estrone sulfate to free estrone, whereas the majority, but not all, breast tumors synthesize estrogen locally via this pathway.     

Cellular vaccines

This project is devoted to the development of novel cellular vaccines designed to treat cancer patients. These cellular vaccines present and enhance immunogens, which will elicit a potent immune response. The goal is to achieve safe and effective immune reaction against the patient's own tumour. (1) Autologous cellular vaccines are prepared by processing circulating blood mononuclear cells outside of the patient's body (ex vivo) to differentiate them into antigen-presenting cells (APCs). Monocyte-derived APCs (MD-APCs) are then grown in the presence of exogenous target antigens (tumour cell debris, or apoptotic bodies) to become fully mature APCs. (2) Functionality for antigen presentation to T cells of ex vivo MD-APCs is evaluated in vivo. (3) Cellular vaccines are tested in selected rodent animal models. Efficiency and immune response are monitored in pertinent experimental systems for cancer. Pharmacological data are generated for clinical investigation. Tolerance and biologic effects are documented in primates. (4) The first clinical trials on cancer patients are taking place in 1998 on melanoma and prostate cancer to validate the concept. Specialized cell processors with dedicated software and standardized controls are being developed and used for the preparation of cellular vaccines. (5) The evaluation of new non-viral vectors and the validation of new non-viral transfection methods of mononuclear cells with marker genes is in progress and will lead to the ex vivo transfection of genes coding for immunostimulating cytokines or for tumour antigens in MD-APCs. Efficiency will be validated in vitro and in animal models. The ex vivo and animal model studies validate the clinical relevance of this new cellular immunotechnology. Clinical validation of individual autologous cellular vaccines in specific indications for which no treatment is presently available will allow the development of cellular and gene immunotherapy for other types of cancers.     

Combination vaccines

The availability of new vaccines for pediatric use provides an unprecedented opportunity to prevent serious infectious diseases and their associated morbidity and mortality. However, each new product entails the need for additional injections that could become so numerous as to discourage the administration of new vaccines. This challenge can be overcome by mixing individual vaccines before delivery such that multiple vaccines are administered as single combination vaccines. Technical, clinical, manufacturing, regulatory and marketing issues relative to combination vaccines in general are the major challenges for ongoing and future development.     

Hepatitis vaccines

Viral hepatitis accounts for substantial morbidity and mortality worldwide, To date, the molecular sequences of six hepatotropic viruses have been described and designated hepatitis A, B, C, D, E, and G. Various methods have been employed to decrease the occurrence of these diseases, and advances in vaccination strategies have aided in prevention of viral hepatitis. There are currently two FDA-approved vaccines licensed for use in the United States, aimed at eradication of hepatitis A and hepatitis B viral infection. A considerable amount of research has been devoted to the development of these vaccines, and progress has been made toward the development of vaccines aimed at the other hepatotropic viruses. In this article, the development and current status of the vaccines directed against the hepatitis viruses are reviewed.     

Influenza vaccines

Varicella pneumonia can endanger the life of pregnant women. We have a case of varicella pneumonia complicating pregnancy in the third trimester. The patient required intubation, early treatment with acyclovir (700 mg/IV every eight hours), as well as the extraction of the fetus by cesarean section before the time gestation was completed. Early treatment with acyclovir has improved hope for these patients.     

DNA vaccines

DNA vaccination against infectious diseases has created a new field of applied molecular immunology. cDNAs for 'protective' protein epitopes can be inserted into vectors containing strong mammalian promoters for high expression. Here we discuss the mechanisms of DNA vaccination and the successful and sometimes unsuccessful applications of DNA vaccination to protect animals against many different viral, bacterial mycoplasmal, protozoal, and worm infections or infestations. DNA immunization has been used to prevent or inhibit tumor development and to inhibit IgE responses by diverting the immune response from Th2 to Th1 helper cell dominance. Advantages and disadvantages of a variety of routes of administration and methods of immunization discussed include the use of the 'gene gun', the delivery of genes by aerosols, and deliberate induction of injury to muscles prior to injection of DNA to enhance gene expression. Vaccination performed using DNA without knowing beforehand the protective epitopes, using 'expression library immunization', is discussed. While this field is bound to expand rapidly for future clinical applications, we try to point out potential pitfalls as well as advantages of this relatively new technology.     

Haemorrhagic septicaemia vaccines

Haemorrhagic septicaemia (HS), an economically important disease of cattle and buffaloes, is caused by Pasteurella multocida (6:B). Vaccination against this disease is widely practised. Plain broth bacterins, or alum precipitated and aluminium hydroxide gel vaccines are administered twice a year since these vaccines offer an immunity of 4-6 months. Many countries use oil adjuvant vaccine (OAV), which gives both a higher degree and a longer duration of immunity up to 1 year. A double emulsion and multiple emulsion vaccine consisting of a thin viscosity have also been experimentally developed that gave an immunity parallel to OAV. Recently, a live vaccine developed from a fallow deer strain (B:3,4) has been used in Myanmar that offers an immunity for more than a year but is not free from constraints. The present review provides information on HS vaccines developed from time to time using whole bacteria or their components. The kinetics and isotype of antibody and cell-mediated immune responses have also been poorly understood so far, and hence information on their role in protection against HS is reviewed.     

Novel vaccines for ectoparasites

Novel vaccines against ectoparasites have the potential to be cost-effective new technology for pest control that avoids some of the real and perceived problems with insecticide and acaricide usage. Nevertheless, their development is in its infancy. A vaccine against the cattle tick Boophilus microplus, the world's first vaccine against an ectoparasite, is in field use in Australia. Considerable effort had gone into the development of a vaccine against the sheep blowfly Lucilia cuprina, while other vaccines are at an earlier stage of development. The identification of critical antigens and their production as effective recombinant proteins remains the greatest hurdle. Characteristics of the few known antigens and the mode of action of the protective immune response are discussed. Development of further vaccines will depend on recognition of likely antigenic targets. The efficacy of such vaccines will depend on the characteristics of the target species, in particular its digestive biology and the way in which the novel vaccine impacts on the parasite population.     

Rotavirus vaccines against diarrhoeal disease

Rotaviruses are responsible for more diarrhoeal disease-associated mortality than any other single agent. Vaccination may therefore hold the key to combating diarrhoeal disease worldwide. Natural immunity to rotavirus infection indicates that rather than protection from reinfection such immunity gives rise to less severe and less frequent attacks of diarrhoea. Early attempts to design a rotavirus vaccine with bovine rotavirus failed because of poor efficacy in some developing countries. Research into rhesus rotavirus, particularly the high-titre rhesus rotavirus tetravalent (RRV-TV) vaccine, has given slightly better results. A stumbling block to truly effective oral vaccines seems to be immunogenicity in developing countries. If efficacy can be ensured by trials in the developing countries, money spent on rotavirus vaccines will be well spent.