The use of both live attenuated or killed whole organisms and their sub-units is discussed, as well as more novel approaches, such as DNA vaccines, recombinant vaccines and epitope-based, or peptide vaccines. The advantages and disadvantages of each approach are presented, eluding to various considerations, such as efficacy, safety and cost of production.
As indicated, these combined strategies led to a long list of vaccines that are presently approved and licensed in the USA, Europe and many other countries, as summarized in a detailed table, which refers also to the pediatric combination vaccines DPT and MMR that are used worldwide, and led to drastic reduction of the incidence of infectious diseases.
Designing Vaccines in the Era of Genomics. Barocchi and Rino Rappuoli.
Genome sequencing has become routine, and modern vaccine design is taking advantage of the accumulating genomic information. Reverse vaccinology, an approach in our institute, is built on genome-based antigen discovery and has largely replaced classical vaccinology methods based on growing and dissecting the microorganism.
The main advantage of the approach is the fast prediction of vaccine candidates. Most of the antigens will be surface exposed proteins, since these antigens are most likely accessible to antibodies. This approach can be applied to non-cultivable microorganisms, something difficult or impossible to do with conventional approaches. When the first reverse vaccinology project was started, in the year , antigen identification was mainly based on bioinformatic analysis of one genome. Since then, the technique has shown its full potential, with the first genome-derived vaccine now in clinical trials and several vaccines in preclinical studies.
In the meantime the approach has been improved with the support of proteomics, functional genomics and comparative genomics.
CORDIS | European Commission
Herein, we provide a description of the complete process: from antigen prediction to high-throughput purification, screening and selection of the vaccine composition. Furthermore, future applications of structural biology to vaccinology are discussed. Antibodies to the pneumococcal polysaccharide capsule protect the host by opsonizing pneumococci for host phagocytes, while antibodies to the meningococcal polysaccharide capsule protect by directly killing meningococci in the presence of complement. In vitro measurement of serum bactericidal antibody SBA against the meningococcus has been used for a long time as a measure of protective immunity.
Technical developments of pneumococcal opsonophagocytosis assays OPA in the past decade permit measurements of opsonic capacity of sera from persons immunized with pneumococcal vaccines. Experience with OPAs shows that opsonic capacities of antisera are better than their antibody levels in predicting vaccine efficacy. Thus, measurements of opsonic capacity could be a surrogate of clinical studies of pneumococcal vaccines.
RNA vaccines: a novel technology to prevent and treat disease
By being the surrogate for clinical studies, the assays for protective function of antibodies would reduce the need for large clinical trials and facilitate vaccine developments and improvements. New Frontiers in the Chemistry of Glycoconjugate Vaccines. Methods for single point attachment of polysaccharides and oligosaccharides to protein carriers and T-cell peptides are briefly reviewed with emphasis on contemporary approaches that involve synthetic oligosaccharides with linker or tether chemistry designed for compatibility with synthetic strategies.
The synthesis and evaluation of conjugate vaccines designed to combat infectious bacterial and fungal diseases, as well as promising attempts to design and test therapeutic cancer vaccine are summarized.
Editorial overview: Vaccines: novel technologies for vaccine development.
The prevailing dogma that protective B-cell epitopes should be comprised of monosaccharides is confirmed for several experimental vaccines including those directed toward Shigell flexneri and Shigella dysenteriae. However, several small epitopes composed of monosaccharide residues are sufficient to induce antibody against the whole organism and to confer protection.
Bacterial Protein Toxin Used in Vaccines. At first glance, the idea of using protein toxins as vaccines against bacterial human diseases seems somewhat of a paradox. However, in some diseases, the severe pathological effects manifested by the causative agents are mediated entirely by protein toxins.
Thus, it seems reasonable to expect that if antibodies could be induced against the protein toxin, they should be effective at preventing severe disease. Of course, the obvious challenge is to detoxify the protein toxin activity without destroying its ability to induce neutralizing antibodies. From an academic point of view, it is ironic that early vaccines against diphtheria, tetanus, and whooping cough were successful without understanding what made them work.
One of the keys to this puzzle was uncovered quite by accident when it was discovered that diphtheria toxin stock preparations stored in large earthenware jars too large to be autoclaved were being detoxified by the residual formalin that leached into the preparations from the formalin-sterilized jars. It took two decades for this discovery to be understood and appreciated to a point where formalin-treatment could be applied to produce toxoid preparations for vaccination.
It then took another half a century to develop the scientific tools and knowledge needed to bring forth the new generation of vaccines, which are highly effective and less reactogenic.
This chapter traces the scientific history, controversies, and development of diphtheria, tetanus, and pertussis vaccines. The development of new effective vaccines, especially those consisting of highly purified antigens, will increasingly require the inclusion of an adjuvant. With over half a century of experience, aluminium containing adjuvants alum will continue to be widely used and until very recently remained the only vaccine adjuvant approved for human use in the US. In recent years a number of studies have started to reveal a more detailed understanding of alum's mechanism of action.
Here we review these recent advances as well as discussing considerations for optimal formulation of the adjuvant. The term "mucosal vaccination" has traditionally been used to describe strategies in which a vaccine is administered via the mucosal route. Unlike parenteral vaccination, mucosal vaccines do not require the use of needles, thus enabling vaccine compliance and reducing logistical challenges and the risks of acquiring blood borne infections. However, despite the great success of mucosal vaccines such as the polio vaccine, several formidable challenges hinder the effective elicitation of immunity against pathogens that invade mucosal sites.
First, in humans the mucosal surfaces of the gut, lung, oral cavity and reproductive tracts are estimated to cover an area of square meters, and thus represent the largest portal of entry for pathogens. Second, the acidic environments of many mucosal sites, and the delineation of mucosal sites by the epithelial barrier, pose challenges to the effective delivery of vaccines.
Third, the mucosal immune system is faced with a somewhat schizophrenic challenge of having to launch robust immunity against mucosal pathogens, whilst restraining immune reactivity to commensals and food antigens. Fourth, the induction of the appropriate type of immune response is critical for effective protection against different pathogens. Fifth, the accurate quantitation of mucosal T and B cell responses pose unique challenges. Despite these challenges, recent advances in our understanding of the innate immunity and its regulation of adaptive immunity at mucosal sites, are beginning to offer new insights into strategies that result in immune protection at mucosal surfaces.
In particular, several recent studies demonstrate that parenteral vaccination with the appropriate adjuvants can induce migration of antigen-specific T and B lymphocytes to mucosal sites. In this chapter, we will review the present mucosal immunization strategies and look at opportunities for exploiting newer developments for devising effective oral vaccines.
Most infectious agents that infect humans do so via mucosal sites, principally the digestive, respiratory and genitourinary tracts. Immune defenses at mucosal surfaces therefore constitute a very vital part of the overall protective responses against these invading pathogens. Vaccines that are administered via the oral routes most proficiently induce the mucosal immune responses. In contrast, parenterally administered vaccines are generally poor inducers of mucosal immunity and are therefore less efficient against infections originating at mucosal surfaces Lamm, ; Levine, However, only a few mucosal vaccines have been approved for human use Table 1 Levine, However, progress in research aimed at understanding the molecular and cellular mechanisms of the mucosal system is presently accelerating, allowing us to design innovative strategies for the development of mucosal vaccines.
The immune response is initiated by dendritic cells DCs and other antigen-presenting cells. These cells are present in nearly all organs and tissues of the body, so that theoretically any organ or tissue could serve as a route for vaccine administration. The choice of route is therefore mainly based on practical aspects. Using conventional needle and syringe the subcutaneous or intramuscular route are standard. The dermis and especially the epidermis are technically more difficult to target, but are likely to gain more interest due to the recent development of micro-needle patches and needle free injection devices.
Vaccine administration via mucosal surfaces such as nasal or oral vaccination represents another option for needle free vaccine administration. While all the above mentioned routes of administration have been proven to work and protect against childhood diseases, influenza and many other infectious agents, the discussion and comparison of these different routes usually focuses on patient convenience, reduction of pain and distress for children, cost and on the possibility for mass vaccination. In this review, however, we would like to focus on how the route of administration can enhance the efficacy of vaccination.
Especially in therapeutic vaccination, i. This is particularly the case in therapeutic cancer vaccines and in allergen specific immunotherapy. Intralymphatic vaccination is a strategy to maximize immunogenicity and therefore vaccine efficacy. The main part of this review will discuss this long known vaccination route and its clinical applicability in therapeutic vaccination. Giuliani and Davide Serruto. Neisseria meningitidis was isolated over one hundred years when Anton Weicshelbaum identified the causative agent of cerebrospinal meningitis.
Since its isolation in , N. Despite over one century since its discovery, scientists have yet to identify a universal vaccine for this deadly bacterium.
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Although vaccines exist for several serogroups of pathogenic N. The genome era has completely changed the way to design vaccines. The availability of the complete genome of microorganisms combined with a novel advanced technology has introduced a new prospective in vaccine research. This novel approach is now known as "Reverse Vaccinology" and N.
The first part is a Collaboration Agreement under which Fiocruz and Emergex will initially carry out a Phase I clinical trial to demonstrate flavivirus vaccine safety. Thereafter, the two parties expect to carry out further clinical studies to test the vaccine in the field. Emergex and Fiocruz will develop vaccines collaboratively to find solutions for various diseases that have not yet been resolved using conventional vaccine approaches. It has a broad range of responsibilities related to the health and wellbeing of the Brazilian population of over million people.
The signing of this MoU is a commitment to explore how our organizations can work together to develop new vaccines against major viral threats that occur in the region. This MoU demonstrates our intention to partner with Emergex to develop a new generation of vaccines. We chose Emergex as its technology enables it to develop and manufacture vaccines in less time and at a fraction of the cost of traditional vaccines.
Its vaccine components are stable at ambient temperatures, avoiding the need for refrigeration, reducing costs and enabling easy transportation — making it particularly suited to treating diseases in remote parts of the world. It has developed a novel and ground-breaking approach to vaccine manufacturing, reverse engineering the immune system and providing that system with data that alters the viral factory.
It uses unique technologies together with cleverly crafted scientific capability to develop and manufacture vaccines at a fraction of the time and cost of conventional vaccines, administered practicably for regions that are infrastructurally-challenged in the developing world as well as for the developed world. Emergex is initially focussed on creating an internationally accessible, clinical grade vaccine repository for use by governments, non-governmental organisations and charities, to act as a first line of defence against existing and newly emerging infectious outbreaks.