Field Of Vaccinology Research Articles

Vaccines: Frontiers in Design and Development

The book by Philippe Moingeon reviews the challenges and opportunities linked with the design and development of novel vaccines. It is a timely publication in light of recent significant advances in the field of vaccinology which go beyond infectious diseases and now include cancers, autoimmune diseases, allergies, neurodegenerative disorders, and metabolic diseases. The editor has assembled a group of 30 scientists from six countries who work in academia, government, or industry and who authored 14 chapters about vaccines.

Research and development of reverse genetics for influenza viruses

Influenza viruses have long been refractory to reconstitution from cloned cDNAs, likely because of the properties of their genome : segmented and negative-stranded RNA, infectious only if in association with the nucleoprotein and polymerase complex. In the late 90s, by relying on an RNA polymerase I dependent transcription system and by cotransfecting 12 or 8 plasmids, reconstitution of the eight ribonucleoproteins of an influenza A virus in a cell was achieved, and production of recombinant viruses was finally obtained. Plasmidbased reverse genetics systems are now widely used to study the molecular mechanisms of virus replication and pathogenicity. They are also proving very useful in the field of vaccinology, as they allow the conception of pandemic vaccines as well as new types of attenuated live vaccines. They could also lead to the use of recombinant influenza viruses as gene delivery vehicles, for prophylactic or therapeutic purposes.

Developing vaccines to counter bioterrorist threats

Large and innovative research programs are underway to define the immune parameters for vaccines against a wide array of pathogens considered to represent a potential bioterrorist threat. However, the development and utilization of such vaccines presents a number of predicaments that have not previously been addressed by the field of vaccinology.

Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know.

The field of vaccinology began in ignorance of how protection was instilled in vaccine recipients. Today, a greater knowledge of immunology allows us to better understand what is being stimulated by various vaccines that leads to their protective effects: that is, their correlates of protection. Here we describe what is known about the correlates of protection for existing vaccines against a range of different viral diseases and discuss the correlates of protection against disease during natural infection with HIV-1. We will also discuss why it is important to design phase 3 clinical trials of HIV vaccines to determine the correlates of protection for each individual vaccine.

Exploiting the redundancy in the immune system: vaccines can mediate protection by eliciting 'unnatural' immunity.

The fields of vaccinology and immunology have had a long-standing and complicated relationship. The view that vaccinology is a branch of immunology is more perception than reality. Vaccinology is older, practical, and often idiosyncratic, with its prime focus on the development of functional vaccines that protect a host against a particular microbe. Immunology is younger, conceptual, and strives to explain how a remarkably complex system recognizes and protects against internal and external threats without committing suicide. Vaccinology has been largely microbe-centered, clinically successful, and mostly empirical, whereas immunology has been largely host-centered, having struggled to translate its theoretical success and potential into clinical applicability. In this commentary, we examine the divide between vaccinology and immunology and put forth the view that vaccines often protect against infectious diseases by eliciting ‘unnatural’ immunity: immune responses that differ from and may even counteract those that arise during the development of natural immunity to

Concepts in immunology and diagnosis of hydatid disease.

Echinococcosis is a cosmopolitan zoonosis caused by adult or larval stages of cestodes belonging to the genus Echinococcus (family Taeniidae). The two major species of medical and public health importance are Echinococcus granulosus and E. multilocularis, which cause cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Both CE and AE are both serious diseases, the latter especially so, with a high fatality rate and poor prognosis if managed inappropriately. This review discusses new concepts and approaches in the immunology and diagnosis of CE, but comparative reference has also been made to AE infection and to earlier pivotal studies of both diseases. The review considers immunity to infection in the intermediate and definitive hosts, innate resistance, evasion of the immune system, and vaccination of intermediate and definitive hosts, and it particularly emphasizes procedures for diagnosis of CE and AE, including the value of immunodiagnostic approaches. There is also discussion of the new advances in recombinant and related DNA technologies, especially application of PCR, that are providing powerful tools in the fields of vaccinology and molecular diagnosis of echinococcosis.

Proteomic study of non-typable Haemophilus influenzae

Non-typable Haemophilus influenzae (NTHi) are small, gram-negative bacteria and are strictly human pathogens, causing acute otitis media, sinusitis and community-acquired pneumonia. There is no vaccine available for NTHi, as there is for H. influenzae type b. Recent advances in proteomic techniques are finding novel applications in the field of vaccinology. There are several protein separation techniques available today, each with inherent advantages and disadvantages. We employed a combined proteomics approach, including sequential extraction and analytical two-dimensional polyacrylamide electrophoresis (2D PAGE), and two-dimensional semi-preparative electrophoresis (2D PE), in order to study protein expression in the A4 NTHi strain. Although putative vaccine candidates were identified with both techniques, 11 of 15 proteins identified using the 2D PE approach were not identified by 2D PAGE, demonstrating the complementarily of the two methods.

Life-style vaccines.

Multiple immunotherapy approaches are under development to treat various chronic diseases or conditions. Thanks to dramatic technological improvements, the field of vaccinology can now extend from prophylaxis to therapy, and from infectious diseases to dysimmune disorders like cancer or autoimmunity, or even to non-immune related conditions, including neurological or cardiovascular disorders. Life-style vaccines defined as vaccines to manage chronic conditions in healthy individuals can, therefore, also be envisaged. Three examples will be reviewed and discussed here, from both technical and ethical aspects: contraceptive vaccines, vaccines to treat addictions, and anti-dental caries vaccines.

New age adjuvants and delivery systems for subunit vaccines.

The dramatic advancements in the field of vaccinology has led to the formulation of chemically well defined vaccines composed of synthetic peptides and recombinant proteins derived from the immunologically dominant regions of the pathogens. Though these subunit vaccines are safer compared to the traditional vaccines they are known to be poorly immunogenic. This necessitates the use of adjuvants to enhance the immunogenicity of these vaccine formulations. The most common adjuvant for human use is alum. Research in the past has focused on the development of systemic immunity using conventional immunization protocols. In the present are, the emphasis is on the development and formulation of alternative adjuvants and delivery systems in generating systemic as well as mucosal immunity. This review mainly focuses on a variety of adjuvants (particulate as well as non-particulate) used with protective antigens of HIV, malaria, plague, leprosy using modified delivery vehicles. The experience of our laboratory and other researchers in this field clearly proves that these new age adjuvants and delivery systems undoubtedly generate enhanced immune response-both humoral and cell mediated. The choice of antigens, the nature of adjuvant used and the mode of delivery employed have a profound effect on the type of immune response generated. Besides the quantity, the quality of the antibodies generated also play a vital role in protection against these diseases. Some of the adjuvants and delivery systems used promoted high titre and affinity antibodies, which were shown to be cytophilic in nature, an important criteria in providing protection to the host. Thus the studies on these adjuvants/delivery systems with respect to various infectious diseases indicate their active role in efficient modulation of immune response along with safety and permissibility.

PROSPECTS FOR A HEPATITIS C VIRUS VACCINE

The scientific and clinical challenges that must be addressed and overcome in developing an efficacious HCV vaccine are substantial but not insurmountable. In a short period, considerable progress has been made in the understanding of HCV pathogenesis, epidemiology, and immunology, and the field of vaccinology in general is making very significant strides in developing new ways to activate and modulate immune responses. Advances in DNA vaccines, novel adjuvants, and recombinant protein technology may be keys in developing creative strategies to generate protective immunity against HCV.

Current paradoxes and changing paradigms in vaccinology

Other than the provision of clean water, food and sanitation, no other deliberate human intervention has prolonged the human life span as much as the provision of vaccines and the control of infectious diseases. Since 1950, 25 vaccines have been licensed in the US, 15 of these for routine universal use in the population. On the horizon are vaccines not only to prevent infectious diseases, but also vaccines against cancer and a host of other human ills. Despite these public health and scientific accomplishments however, the manner in which we think about, develop and apply vaccines to the public health has common heuristic flaws which prevent realizing the full benefits of vaccines to society. This paper will discuss a number of current paradoxes and changing paradigms related to the field of vaccinology.

Research Priorities in the Field of Vaccinology

No abstract

Genetic immunization.

Genetic immunization, the latest addition to the field of vaccinology, has shown, in a number of animal models, to be an efficacious approach to induce protective immunity to infectious diseases. The advantages of DNA vaccines are their ease of construction, the low expanse of mass production, their high temperature stability, and their ability to induce a full spectrum of exceptionally long-lasting immune responses including cytolytic T cells. Their potential disadvantages are putative safety issues such as integration into the host cell genome. The slow development of the immune response to genetic immunization will make these vaccines unsuitable for treatment of some infectious disease such as postexposure vaccination to rabies virus, where a rapid immune response is warranted. Although only time will tell if genetic immunization provides a viable alternative for human immunization, in the meantime this approach provides immunologists with a powerful tool to gain further insight in the mechanisms that drive primary immune responses.

Development of Combined Vaccines: Manufacturers' Viewpoint

Abstract. Rapid and exciting research breakthroughs in the fields of immunology and molecular biology in recent years have greatly enhanced the potential for developing new vaccines or improving existing ones. The resulting rising number of diseases that can be prevented by vaccination, coupled with the growing trend of preferring cost-effective preventive medical interventions over expensive therapeutic modalities, has increased the complexity of administering to all those who need them, the many different vaccines that will soon be available. Hence attention in the field of vaccinology is now focusing on the development of combined vaccines that, in a few inoculations, can elicit protection against as many diseases as possible. Some of the recent achievements, future objectives and difficulties of vaccine manufacturers in the development of combined vaccines are surveyed.