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PubMed1978

Recent developments in vaccination against bovine brucellosis.

Recent research in vaccination against bovine brucellosis has been directed towards reducing the serological response to vaccination and to developing serological tests better able to distinguish vaccinal titres from those resulting from field infection. In the case of strain 19 vaccination, developments such as reducing the dose of vaccine and improving serological tests have so reduced the serological response as to allow adult vaccination to be carried out in combination with eradiction by test and slaughter. B. abortus 45/20 vaccine is being increasingly used as a combined diagnostic aid and protective agent. Progress has been made in identifying antibodies produced in response to this vaccine.

Agglutination Tests↗

PubMed1997

Prospects for the development of fungal vaccines.

In an era that emphasizes the term "cost-effective," vaccines are the ideal solution to preventing disease at a relatively low cost to society. Much of the previous emphasis has been on childhood scourges such as measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type b. The concept of vaccines for fungal diseases has had less impact because of the perceived limited problem. However, fungal diseases have become increasingly appreciated as serious medical problems that require recognition and aggressive management. The escalation in the incidence and prevalence of infection has prompted a renewed interest in vaccine development. Herein, I discuss the most recent developments in the search for vaccines to combat fungal infections. Investigators have discovered several inert substances from various fungi that can mediate protection in animal models. The next challenge will be to find the suitable mode of delivery for these immunogens.

Adjuvants, Immunologic↗

PubMed2002

Development of cytomegalovirus vaccines: prospects for prevention of congenital CMV infection.

Congenital cytomegalovirus (CMV) infection is an important cause of hearing, cognitive, and motor impairments that cannot be effectively prevented or treated by any current medical or public health interventions. A review of priorities for vaccine development by The Institute of Medicine of the National Academy of Sciences concluded that a vaccine to prevent congenital CMV infection should be a top priority for the United States. Evidence from clinical studies indicates that immunity to CMV can reduce the frequency and severity of disease. Laboratory investigations have identified structural and nonstructural CMV proteins that play a key role in eliciting protective immunity. The rationale for development of a CMV vaccine has been strengthened further by studies in experimental animals demonstrating the ability of immunization with subunit vaccines to prevent disease and transplacental transmission of virus. At least 4 CMV vaccines are in clinical trials, and advances in biotechnology are paving the way for additional novel vaccines.

Cytomegalovirus↗

PubMed2004

Developmental immunology and vaccines: cellular immune development and future vaccine strategies.

This section deals with how new knowledge of the development of cellular immunity in the neonatal period informs vaccine development and reviews the immune responses of the most vulnerable group of newborns, those born prematurely, to vaccines. It describes how the development of future vaccine strategies relies on a detailed understanding of immune ontogeny and the potential consequences of intervention on developing cellular immune responses.

Dendritic Cells↗

PubMed1999

The societal value of vaccination in developing countries.

The vaccination of children against childhood illnesses not only carries the obvious medical and economic benefits, but there exists numerous indirect and often far reaching added societal benefits. In developing countries, vaccination forms the basis of village operated primary health care (PHC) activities leading to a sustained PHC programme. Vaccination programmes provide an opportunity for the provision of other primary care services, as it can be the only recurring activity in primary care, that brings mother and child into contact with health services on a predictable and frequent basis. Vaccination leads to a direct and measurable reduction of child mortality rates and this has been proven to families and communities, resulting in families choosing to have fewer children. Vaccination becomes an opportunity for a higher standard of living as it encourages smaller families and in this way contributes to successes In family planning programmes. The vaccination of children has a great impact on the lives of women in developing countries as they are the principle carers of children. Protecting the lives of children directly through vaccination and through other PHC activities is a major strategy towards improving the lives of women as it liberates their time, energy and resources. The opportunity and provision of vaccination empowers women to protect their own health and that of their children through their own actions, giving an added psychological feeling of control and empowerment in their lives. Therefore, while vaccination services can be delivered alone, they are best delivered along with other services needed by children in their first year of life and by pregnant women: the persons who constitute the priority groups for primary health care services in the developing world. In addition to the monitoring of the growth of the child, the use of oral re-hydration to treat diarrhoea and the promotion of breast-feeding, these services may include malaria treatment and prophylaxis, and counselling with respect to child spacing, nutrition during pregnancy, weaning practices, and clean water and sanitation.

Child↗

PubMed2004

Immune profiling of leprosy and tuberculosis patients to 15-mer peptides of Mycobacterium leprae and M. tuberculosis GroES in a BCG vaccinated area: implications for development of vaccine and diagnostic reagents.

Mycobacterium leprae (ML) GroES has been shown to induce strong T cell responses in tuberculoid as well as in exposed healthy contacts of leprosy patients, and therefore this antigen has been the focus of study as a potential vaccine candidate. Paradoxically, we have shown that ML GroES also induces extremely high titres of IgG1 antibody in leprosy patients across the disease spectrum, a response associated with disease progression. IgG1 antibodies in leprosy also show a negative association with interferon-gamma, a critical T cell cytokine responsible for macrophage activation and intracellular killing of mycobacteria. We therefore queried if antibody and T cell responses were being evoked by different epitopes in ML GroES proteins. To address the issue of epitope recognition in mycobacterial diseases, we have analysed 16 peptides (15-mer peptides) spanning the entire ML and M. tuberculosis GroES protein in leprosy (n = 19) and tuberculosis (n = 9) patients and healthy endemic controls (n = 8). Our analysis demonstrates clearly that the dominant peptides evokingT cell and IgG subclass antibodies were different. The target of both T and B cell responses were cross-reactive epitopes in all groups. Differences in disease and healthy states related to the strength (mean intensity) of the T cell and antibody response. IgG1 and IgG3 antibodies were associated with disseminated disease and IgG 2 and IgG4 with disease limitation. Such comprehensive immune profiling of antigen-specific responses is critical to understanding the disease pathogenesis and also if these reagents are to be exploited for either diagnostic or vaccine purposes.

Amino Acid Sequence↗

PubMed1996

The development of malaria vaccines: SPf66--what next?

Malaria, especially that caused by Plasmodium falciparum, is the most important parasitic disease of man. The complexity of the life cycle, the transmission dynamics in different endemic settings, and the spread of resistance to various drugs by the parasite and to insecticides by the vector render control strategies very difficult. An effective vaccine against malaria would represent a major strengthening of control. Research efforts to identify and select antigens for vaccine development have been substantial, particularly in the past 20 years. Various molecules from the pre-erythrocytic, asexual blood and sexual stages have been described and tested in experimental systems, and some may become interesting vaccine candidates. A crucial step was taken with the development of SPf66, a synthetic polypeptide based on pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum. The concept of the SPf66 vaccine is not the prevention of clinical malaria but reduction of morbidity, and it is thus suitable for endemic areas, particularly Africa. The clinical phase III trials so far undertaken in Latin America and in Africa have clearly documented the safety, immunogenicity and partial efficacy of SPf66 against clinical malaria. The efficacy estimates of all trials are below those we generally demand from vaccines and when we aim to induce sterile immunity. Therefore, a large number of issues at the field and laboratory levels, such as ways of optimizing efficacy (doses, timing, age of vaccination), and understanding the mechanisms of action and effectiveness, need to be investigated before one can consider the public health use of SPf66 as a component of an integrated malaria control programme. The substantial tasks ahead involve (1) improving the vaccine which we have and (2) devising and testing new vaccines which may prove more efficacious. Malaria vaccines are now a reality, and the achievements of SPf66 to date, the ongoing research efforts with other vaccine candidates, and the potential of DNA vaccines make it possible to predict that widespread use of an efficacious vaccine no longer represents an unrealistic target.

Adolescent↗

PubMed2001

What are today's orphaned vaccines?

Development costs for new biological agents are increasing, and the time span from laboratory research to introduction of a product on the world market is becoming ever longer. Complex regulatory requirements add barriers and additional costs to early introduction abroad. This results in reluctance by manufacturers to undertake development of a vaccine that will be used for a tropical disease in only the public sector of a poor country. The chances of recovery of huge investment costs before patents expire are not good, unless such a new vaccine can also be sold at high cost in North America and Europe. These are some of the reasons that we still do not have a modern Japanese encephalitis vaccine or products against malaria and dengue fever. Many tropical countries must find a way to develop their own vaccine production facilities. Innovative help for technology transfer will have to be forthcoming, or many new life-saving products will never bridge the gap between research unit and production.

Developed Countries↗

PubMed2002

Experience with the clinical development of influenza vaccines for potential pandemics.

During normal interpandemic influenza seasons, immune responses to vaccines are quite predictable and meet the licensing criteria of the European Union (EU) Committee for Proprietary Medicinal Products (CPMP). In a pandemic situation, large sections, if not all of the community will be immunologically naïve and therefore new immunisation strategies will be needed. In 1976 and 1977 H1N1 vaccines were prepared and tested clinically. To stimulate 'protective' antibody responses, two doses of vaccine were needed in people below the age of 24 years (no previous experience of H1N1 virus), whereas one conventional dose was adequate in older people. In 1997, the highly pathogenic avian influenza H5N1 virus caused widespread concern when it infected man, with lethal effects. Due to safety concerns it was necessary to adopt new strategies for vaccine development and one such strategy was to produce vaccine from an avirulent H5N3 virus, A/Duck/Singapore-Q/F119-2/97. Clinical trials of a subunit vaccine prepared from A/Duck/Sing/97 virus revealed that even two doses of twice the normal vaccine concentration (i.e. 30 micro g haemagglutinin) were poorly immunogenic, whereas an H5N3 vaccine adjuvanted with microfluidised emulsion (MF) 59 stimulated antibody levels that complied with CPMP criteria after two half strength doses (i.e. 7.5 micro g haemagglutinin).

Clinical Trials as Topic↗

PubMed1999

Progress in the development of malaria vaccines: context and constraints.

Major technical advances in the field of vaccine development have culminated in an impressive array of prototype vaccines that may well provide 'proof of principle' that vaccines against all life-cycle stages may induce a degree of protection against malaria. As the mechanisms responsible for protection against this disease are not known, and vaccines for populations at greatest risk will be applied in the presence of ongoing infection and a degree of concomitant immunity, it is essential for us to learn from the 'experiments of nature' about acquired and ongoing immunity in order to determine when and how these vaccines may be applied. Successful interventions with chemoprophylaxis or vector control have provided obvious lessons and highlight the importance of recognising the lack of correlation between infection, clinical disease and mortality. Vaccines inducing sterile immunity raise concerns about rebound mortality in populations who will undoubtedly be re-challenged later in life, hence the need to review supplementary or alternative strategies for reducing disease through immune responses to toxins or molecules inducing pathology by adherence to host endothelium. Following antigen selection there are many challenges in choosing methods of antigen delivery and adjuvants, and measuring vaccine efficacy. A successful vaccine would need to be delivered through a national programme in the context of implementation of a wide range of components required for an effective control strategy.

Humans↗

PubMed2003

Developments in cancer vaccination.

The clinical application of cancer vaccines has progressed steadily from the rapid preclinical, technological advances of recent years. Cancer vaccine development has followed to some extent the pattern of vaccination for infectious disease, although features, such as the need to treat established disease in the face of immune evasion, vary. The necessity of conducting safety testing of new therapies in advanced cancer patients rather than in early-diagnosed patients often means that therapeutic benefit is seldom observed. Data that support even limited clinical efficacy are therefore encouraging. Initial approaches using whole irradiated tumor cells continue with some success, although there has been some refinement involving the use of tumor antigens and their subunits in a protein/peptide form (often via manipulated dendritic cells) or as DNA and RNA delivered naked or by viruses. Appropriate modes of boosting the immune system and immune conditioning appear important. Cancer vaccination research is likely to continue along many paths before any approaches become mainstream.

Animals↗

PubMed2004

Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines.

BACKGROUND: In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people. The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. METHODS: We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. FINDINGS: A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. INTERPRETATION: The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.

Animals↗

PubMedDate not supplied

[Achievements and problems in the development of malaria vaccines].

Malaria continues as a public health problem in the world. The control strategy by insecticides against the vector arthropod and antimalaria drugs have not been enough to eradicate this illness, which is the cause of over a million deaths every year throughout the world. In the latest years the recombinant DNA technology and the synthesis of peptides for antimalaria vaccine elaboration has been used specially against Plasmodium falciparum, which is the most aggressive of the human species of Plasmodium. Encouraging results in this field have been obtained. Some molecules have been characterized and synthetized which are considered worthy vaccine candidates because of their suitable immunogenicity, safety and immunoprotective capacity. These molecules belong to sexual and merozoite phases of the parasite, meanwhile molecules isolated from the sporozoitic phase, such as circunsporozoitic protein, have posed the greatest problems for the vaccine development.

Amino Acid Sequence↗

PubMed1990

Current issues in the development of a vaccine against HIV infection.

There are a variety of complex issues involved in current efforts to design and test a safe and effective vaccine against HIV-1 infection. Although a number of important insights already have been gained, future advances in vaccine development must overcome a number of obstacles. These include the lack of a suitable animal model for HIV-1 infection and our incomplete understanding of the protective immune response in this disease as well as uncertainties about the most appropriate strategy for large-scale testing of promising candidate vaccines.

Adjuvants, Immunologic↗

PubMed2000

Progress toward the development of a vaccine to prevent Moraxella (Branhamella) catarrhalis infections.

Moraxella catarrhalis is a major cause of otitis media and respiratory disease. Vaccine development is at the antigen identification stage. This review examines the more promising antigens, including the 200K protein, the hemagglutinins, the lactoferrin-binding proteins, the UspA proteins, the CopB protein, the transferrin-binding proteins, the CD protein, the E protein and lipooligosaccharide conjugates. Clinical testing of some of these antigens should begin soon.

Animals↗

PubMed2006

Assembly of pseudorabies virus genome-based transfer vehicle carrying major antigen sites of S gene of transmissible gastroenteritis virus: potential perspective for developing live vector vaccines.

Two severe porcine infectious diseases, pseudorabies (PR) and transmissible gastroenteritis (TGE) caused by pseudorabies virus (PRV) and transmissible gastroenteritis virus (TGEV) respectively often result in serious economic loss in animal husbandry worldwide. Vaccination is the important prevention means against both infections. To achieve a PRV genome-based virus live vector, aiming at further TGEV/PRV bivalent vaccine development, a recombinant plasmid pUG was constructed via inserting partial PK and full-length gG genes of PRV strain Bartha K-61 amplified into pUC119 vector. In parallel, another recombinant pHS was generated by introducing a fragment designated S1 encoding the major antigen sites of S gene from TGEV strain TH-98 into a prokaryotic expression vector pP(RO)EX HTc. The SV40 polyA sequence was then inserted into the downstream of S1 fragment of pHS. The continuous region containing S1fragment, SV40 polyA and four single restriction enzyme sites digested from pHS was subcloned into the downstream of gG promoter of pUG. In addition, a LacZ reporter gene was introduced into the universal transfer vector named pUGS-LacZ. Subsequently, a PRV genome-based virus live vector was generated via homologous recombination. The functionally effective vector was purified and partially characterized. Moreover, the potential advantages of this system are discussed.

Animals↗

PubMed2005

Malaria vaccines: using models of immunity and functional genomics tools to accelerate the development of vaccines against Plasmodium falciparum.

Naturally acquired immunity and immunity acquired after immunization with attenuated parasites indicate that a vaccine against malaria is feasible. Several obstacles have stymied malaria vaccine development, among them our poor understanding of protective immunity and technical difficulties for studying gene and protein expression in the Plasmodium falciparum parasite. Pregnancy malaria offers a model approach for vaccine development: recent findings have elucidated the basis for disease pathogenesis and protective immunity in this syndrome, and this understanding has focused the effort to identify the optimal antigens for a pregnancy malaria vaccine. In parallel, functional genomics tools are overcoming several of the obstacles for studying protein expression in the malaria parasite, vastly accelerating the pace for antigen discovery. Together, these conceptual and technological advances allow a rational approach to vaccine antigen selection, in which a finite number of antigens are selected from the entire genome by merit of the expression patterns and specific features. These candidate antigens are then subjected to detailed studies according to criteria established by the understanding of pathogenesis and protective immunity, to identify the optimal antigens for inclusion in subunit vaccines.

Animals↗

PubMed2004

Current advances in HIV vaccines.

Development of a safe and preventive HIV-1 vaccine is a high priority. Recent advances in HIV vaccine development include an improved understanding of HIV envelope structure, development of techniques that enable a detailed analysis of vaccine-induced immune responses in humans, expansion of the pipeline of promising candidate vaccines, and completion of the first vaccine efficacy trials. A common feature of several preventive vaccine strategies in early clinical trials is their ability to attenuate clinical disease rather than completely prevent HIV infection in nonhuman primates. One or more candidate vaccines will likely advance into efficacy trials within the next few years, while efforts to identify new designs that induce broadly neutralizing antibodies continue with incremental success.

AIDS Vaccines↗