Vaccine Developments
Streptococcus pneumoniae Vaccine
Vaccines against Streptococcus pneumoniae
from James C. Paton writing in Vaccine Design: Innovative Approaches and Novel Strategies
Existing vaccines against Streptococcus pneumoniae are targeted at the capsular polysaccharide (PS) of which there are 91 distinct serotypes. Polyvalent purified PS vaccines are immunogenic in healthy adults, but not in high risk groups such as young children and the elderly. Development of PS-protein conjugate vaccines has overcome the poor immunogenicity of PS in children, but the protection imparted is strictly serotype-specific, and the number of included serotypes is even more restricted than in the PS vaccine formulations. Widespread introduction of conjugate vaccines in developed countries has dramatically reduced the incidence of invasive pneumococcal disease due to serotypes included in the vaccine. However, these benefits are being eroded by increases in the incidence of disease caused by non-vaccine serotypes. Conjugate vaccines are also expensive, limiting their use in developing countries, where the burden of pneumococcal disease is greatest. Clearly, there is an urgent need to develop alternative pneumococcal vaccines that are (i) inexpensive, (ii) immunogenic in young children, and (iii) provide protection against all pneumococci regardless of serotype. Of particular importance are vaccines comprising pneumococcal proteins that contribute to virulence and are common to all serotypes.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Bacterial Polysaccharides: Current Innovations and Future Trends
from James C. Paton writing in Vaccine Design: Innovative Approaches and Novel Strategies
Existing vaccines against Streptococcus pneumoniae are targeted at the capsular polysaccharide (PS) of which there are 91 distinct serotypes. Polyvalent purified PS vaccines are immunogenic in healthy adults, but not in high risk groups such as young children and the elderly. Development of PS-protein conjugate vaccines has overcome the poor immunogenicity of PS in children, but the protection imparted is strictly serotype-specific, and the number of included serotypes is even more restricted than in the PS vaccine formulations. Widespread introduction of conjugate vaccines in developed countries has dramatically reduced the incidence of invasive pneumococcal disease due to serotypes included in the vaccine. However, these benefits are being eroded by increases in the incidence of disease caused by non-vaccine serotypes. Conjugate vaccines are also expensive, limiting their use in developing countries, where the burden of pneumococcal disease is greatest. Clearly, there is an urgent need to develop alternative pneumococcal vaccines that are (i) inexpensive, (ii) immunogenic in young children, and (iii) provide protection against all pneumococci regardless of serotype. Of particular importance are vaccines comprising pneumococcal proteins that contribute to virulence and are common to all serotypes.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Bacterial Polysaccharides: Current Innovations and Future Trends
Vaccines for Neglected Diseases
Category: Vaccines | Immunology
Vaccines for Neglected Diseases
from Allan Saul writing in Vaccine Design: Innovative Approaches and Novel Strategies
Infectious diseases exert a major burden of disease in developing countries. While better use of existing vaccines would make an appreciable difference, the greatest burden is caused by diseases for which we currently have no vaccines. The picture, especially in children, is dominated by diarrheal and respiratory diseases. Paradoxically diseases have relatively low priority for funding in absolute terms, and especially in relationship to the burden of disease. Thus, new vaccines for these neglected diseases need both innovative scientific solutions and innovative development schemes involving scientific institutes, public financing and industrial input. The industrial input is critical: not only will vaccine manufacture require an industrial partner, but the knowledge to efficiently undertake the technical and clinical development leading to vaccine production largely resides in industry. A potentially important development in this area has been the recent formation of Industry Linked Vaccine Institutes: For example, The Novartis Vaccines Institute for Global Health and the Hilleman Laboratories. These are an important conduit for applying industrial know how for developing commercial vaccines to the pressing need for vaccines for neglected diseases of developing countries.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
from Allan Saul writing in Vaccine Design: Innovative Approaches and Novel Strategies
Infectious diseases exert a major burden of disease in developing countries. While better use of existing vaccines would make an appreciable difference, the greatest burden is caused by diseases for which we currently have no vaccines. The picture, especially in children, is dominated by diarrheal and respiratory diseases. Paradoxically diseases have relatively low priority for funding in absolute terms, and especially in relationship to the burden of disease. Thus, new vaccines for these neglected diseases need both innovative scientific solutions and innovative development schemes involving scientific institutes, public financing and industrial input. The industrial input is critical: not only will vaccine manufacture require an industrial partner, but the knowledge to efficiently undertake the technical and clinical development leading to vaccine production largely resides in industry. A potentially important development in this area has been the recent formation of Industry Linked Vaccine Institutes: For example, The Novartis Vaccines Institute for Global Health and the Hilleman Laboratories. These are an important conduit for applying industrial know how for developing commercial vaccines to the pressing need for vaccines for neglected diseases of developing countries.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
Serogroup B Meningococcus Vaccine
The First Vaccine Obtained Through Reverse Vaccinology: The Serogroup B Meningococcus Vaccine
from Jeannette Adu-Bobie, Beatrice Aricò, Marzia M. Giuliani and Davide Serruto writing in Vaccine Design: Innovative Approaches and Novel Strategies
Neisseria meningitidis was isolated over one hundred years when Anton Weicshelbaum identified the causative agent of cerebrospinal meningitis. Since its isolation in 1887, N. meningitidis has been recognized to cause endemic cases, case clusters, epidemics and pandemics of meningitis and devastating septicaemia. Despite over one century since its discovery, scientists have yet to identify a universal vaccine for this deadly bacterium. Although vaccines exist for several serogroups of pathogenic N. meningitidis, serotype B (MenB) has eluded scientists for decades, until the advent of genomics. 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. meningitidis can be considered the first successful example of its application. A recent review describes the successful story of the development of the serogroup B vaccine, starting from the analysis of genome and finishing with the results obtained in clinical trials.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Neisseria: Molecular Mechanisms of Pathogenesis
from Jeannette Adu-Bobie, Beatrice Aricò, Marzia M. Giuliani and Davide Serruto writing in Vaccine Design: Innovative Approaches and Novel Strategies
Neisseria meningitidis was isolated over one hundred years when Anton Weicshelbaum identified the causative agent of cerebrospinal meningitis. Since its isolation in 1887, N. meningitidis has been recognized to cause endemic cases, case clusters, epidemics and pandemics of meningitis and devastating septicaemia. Despite over one century since its discovery, scientists have yet to identify a universal vaccine for this deadly bacterium. Although vaccines exist for several serogroups of pathogenic N. meningitidis, serotype B (MenB) has eluded scientists for decades, until the advent of genomics. 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. meningitidis can be considered the first successful example of its application. A recent review describes the successful story of the development of the serogroup B vaccine, starting from the analysis of genome and finishing with the results obtained in clinical trials.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Neisseria: Molecular Mechanisms of Pathogenesis
Mucosal Vaccines
Category: Immunology | Vaccines
Mucosal Vaccines
from Rajesh Ravindran and Bali Pulendran writing in Vaccine Design: Innovative Approaches and Novel Strategies
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 400 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. These advances promise to accelerate the development and testing of new mucosal vaccines against many diseases including HIV/AIDS. 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 (Rajesh Ravindran and Bali Pulendran). However, only a few mucosal vaccines have been approved for human use (Table 1, Rajesh Ravindran and Bali Pulendran)). 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.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
from Rajesh Ravindran and Bali Pulendran writing in Vaccine Design: Innovative Approaches and Novel Strategies
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 400 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. These advances promise to accelerate the development and testing of new mucosal vaccines against many diseases including HIV/AIDS. 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 (Rajesh Ravindran and Bali Pulendran). However, only a few mucosal vaccines have been approved for human use (Table 1, Rajesh Ravindran and Bali Pulendran)). 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.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
Vaccine Adjuvants
Category: Vaccines | Immunology
Vaccine Adjuvants
from David A. G. Skibinski and Derek T. O'Hagan writing in Vaccine Design: Innovative Approaches and Novel Strategies
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. There is a the need for more potent adjuvants than alum, with particular emphasis on the discovery and development of MF59, an emulsion based vaccine adjuvant which as been licensed for more than ten years in more than 20 countries, for use in an influenza vaccine focused on elderly subjects (Fluad).
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
from David A. G. Skibinski and Derek T. O'Hagan writing in Vaccine Design: Innovative Approaches and Novel Strategies
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. There is a the need for more potent adjuvants than alum, with particular emphasis on the discovery and development of MF59, an emulsion based vaccine adjuvant which as been licensed for more than ten years in more than 20 countries, for use in an influenza vaccine focused on elderly subjects (Fluad).
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
Toxin Used in Vaccines
Category: Immunology | Vaccines
Bacterial Protein Toxin Used in Vaccines
from Jerry M. Keith writing in Vaccine Design: Innovative Approaches and Novel Strategies
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. A recent review traces the scientific history, controversies, and development of diphtheria, tetanus, and pertussis vaccines.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Microbial Toxins: Current Research and Future Trends
from Jerry M. Keith writing in Vaccine Design: Innovative Approaches and Novel Strategies
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. A recent review traces the scientific history, controversies, and development of diphtheria, tetanus, and pertussis vaccines.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies | Microbial Toxins: Current Research and Future Trends
Glycoconjugate Vaccines
New Frontiers in the Chemistry of Glycoconjugate Vaccines
from David R. Bundle writing in Vaccine Design: Innovative Approaches and Novel Strategies
Methods for single point attachment of polysaccharides and oligosaccharides to protein carriers and T-cell peptides are important in vaccine design. Contemporary approaches involve synthetic oligosaccharides with linker or tether chemistry designed for compatibility with synthetic strategies. Current research involves the synthesis and evaluation of conjugate vaccines designed to combat infectious bacterial and fungal diseases, as well as the design and testing of therapeutic cancer vaccine. The prevailing dogma that protective B-cell epitopes should be comprised of 10-20 monosaccharides is confirmed for several experimental vaccines including those directed toward Shigell flexneri and Shigella dysenteriae. However, several small epitopes composed of 3-5 monosaccharide residues are sufficient to induce antibody against the whole organism and to confer protection.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
from David R. Bundle writing in Vaccine Design: Innovative Approaches and Novel Strategies
Methods for single point attachment of polysaccharides and oligosaccharides to protein carriers and T-cell peptides are important in vaccine design. Contemporary approaches involve synthetic oligosaccharides with linker or tether chemistry designed for compatibility with synthetic strategies. Current research involves the synthesis and evaluation of conjugate vaccines designed to combat infectious bacterial and fungal diseases, as well as the design and testing of therapeutic cancer vaccine. The prevailing dogma that protective B-cell epitopes should be comprised of 10-20 monosaccharides is confirmed for several experimental vaccines including those directed toward Shigell flexneri and Shigella dysenteriae. However, several small epitopes composed of 3-5 monosaccharide residues are sufficient to induce antibody against the whole organism and to confer protection.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
Protective Capacity of Antibodies
Category: Vaccines | Immunology
New Analytical Approaches for Measuring Protective Capacity of Antibodies
from Moon H. Nahm and Carl E. Frasch writing in Vaccine Design: Innovative Approaches and Novel Strategies
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. 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.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies
from Moon H. Nahm and Carl E. Frasch writing in Vaccine Design: Innovative Approaches and Novel Strategies
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. 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.
Further reading: Vaccine Design: Innovative Approaches and Novel Strategies