DNA Vaccines: History, Molecular Mechanisms and Future Perspectives.

The history of DNA vaccine began as early as the 1960s with the discovery that naked DNA can transfect mammalian cells in vivo. In 1992, the evidence that such transfection could lead to the generation of antigen-specific antibody responses was obtained and supported the development of this technology as a novel vaccine platform. The technology then attracted immense interest and high hopes in vaccinology, as evidence of high immunogenicity and protection against virulent challenges accumulated from several animal models for several diseases. In particular, the capacity to induce T-cell responses was unprecedented in non-live vaccines. However, the technology suffered its major knock when the success in animals failed to translate to humans, where DNA vaccine candidates were shown to be safe but remained poorly immunogenic, or not associated with clinical benefit. Thanks to a thorough exploration of the molecular mechanisms of action of these vaccines, an impressive range of approaches have been and are currently being explored to overcome this major challenge. Despite limited success so far in humans as compared with later genetic vaccine technologies such as viral vectors and mRNA, DNA vaccines are not yet optimised for human use and may still realise their potential.

DNA Vaccines - A Modern Gimmick or a Boon to Vaccinology?

The reports in 1993 that naked DNA encoding viral genes conferred protective immunity came as a surprise to most vaccinologists. This review analyses the expanding number of examples where plasmid DNA induces immune responses. Issues such as the type of immunity induced, mechanisms of immune protection, and how DNA vaccines compare with other approaches are emphasized. Additional issues discussed include the likely means by which DNA vaccines induce CTL, how the potency and type of immunity induced can be modified, and whether DNA vaccines represent a practical means of manipulating unwanted immune response occurring during immunoinflammatory diseases. It seems doubtful if DNA vaccines will replace currently effective vaccines, but they may prove useful for prophylactic use against some agents that at present lack an effective vaccine. DNA vaccines promise to be valuable to manipulate the immune response in situations where responses to agents are inappropriate or ineffective.

From empiricism to rational design: a personal perspective of the evolution of vaccine development.

Vaccination, which is the most effective medical intervention that has ever been introduced, originated from the observation that individuals who survived a plague or smallpox would not get the disease twice. To mimic the protective effects of natural infection, Jenner - and later Pasteur - inoculated individuals with attenuated or killed disease-causing agents. This empirical approach inspired a century of vaccine development and the effective prophylaxis of many infectious diseases. From the 1980s, several waves of new technologies have enabled the development of novel vaccines that would not have been possible using the empirical approach. The technological revolution in the field of vaccination is now continuing, and it is delivering novel and safer vaccines. In this Timeline article, we provide our views on the transition from empiricism to rational vaccine design.

Pesquisa e inovação em saúde: o caso da vacina de DNA contra o vírus da febre amarela / Health research and innovation: the case of the DNA vaccine against yellow fever virus

Diante da necessidade de se produzir mais inovações tecnológicas voltadas à saúde pública no Brasil, analisou-se o caso da vacina de DNA contra o vírus da febre amarela, desenvolvida na Fiocruz-Pernambuco entre 2005 e 2008. Foram elaboradas estruturas analíticas específicas e os dados foram coletados mediante entrevistas, análise documental, bibliográfica e de registros em arquivos. Verificou-se que no ano 2000 a organização era mais voltada à geração de conhecimentos, mas a partir de 2002 ocorreram os seguintes eventos que levaram ao estabelecimento das parcerias e das linhas e técnicas de pesquisa que possibilitaram a invenção da vacina: adoção de uma nova estratégia, contratação de consultor em universidade estrangeira, criação de laboratório, priorização de alocação de recursos, captação de recursos em projetos colaborativos, manutenção de instalações em padrões de qualidade, seleção de profissionais com habilidades complementares, e promoção de incorporação de novas tecnologias de pesquisa. A invenção se baseou em informações oriundas da formação educacional dos inventores, experiência em instituição estrangeira, ferramentas de bioinformática, literatura científica, análise e experimentação dentro da organização e em instituições parceiras. As próximas etapas do projeto necessitarão de competências nas áreas de marketing estratégico, pesquisa da vacina candidata, Pesquisa e Desenvolvimento da formulação, propriedade intelectual, desenv. do processo, desenv. de negócios, desenv. analítico, desenv. de sistemas e testes biológicos, assuntos regulatórios no País, 'upstream process', 'downstream processing', formulação e envase, desenv. clínico, e coordenação/integração. No entanto, a capacitação nacional parece frágil em dez dessas funções

Assim, para produzir no País mais inovações tecnológicas voltadas à saúde pública, é necessário, além da capacitação das instituições de pesquisa, a construção de novas aptidões nas demais instituições ligadas ao complexo industrial da saúde nacional

[On three revolutions of vaccine].

Since the Chinese inuented the uaniolation with human pox vaccine and Jenner invented the vaccine for cowpox, the great achievements of vaccination in preventing and treating many diseases are universally acknowledged. In 1995, the New York Academy of Sciences of America sponsored a symposium on DNA (deoxyribonucleic acid) vaccine, which is called the third revolution of vaccine and new epoch for vaccinology. The first revolution was the invention of inactivated vaccines and live attenuated vaccines represented by Pasteur at the end of the nineteenth century. The second one was the subunit of vaccine prepared by DNA recombination technique and techniques of protein chemistry in 1980s.

Allergen immunotherapy in ENT: historical perspective.

The origins of immunology and allergy are founded upon the early 19th century microbiological studies of Jenner and Pasteur. It was discovered that the immune system could cause harm. The subspecialty of allergy began with the coining of the term by Von Pirquet in 1906 to describe disorders resulting from hyper-reaction to normally innocuous environmental agents. Understanding the scientific basis of the immune system and allergy allowed Noon and Freeman, and later Cooke, to develop allergen immunotherapy. Initially the technique was crude, but with the subsequent key discovery of IgE, more accurate methods of diagnosis (such as the radioallergosorbent test (RAST)) and treatment ensued. The efficacy of specific immunotherapy has been demonstrated by many double-blind trials culminating in the WHO position paper. DNA recombinant technology has provided detailed molecular understanding of allergic disorders, which has resulted in several novel methods of immunotherapy that are potentially safer and more effective. Use of recombinant allergens, T-cell peptides, DNA vaccination with CpG motifs or plasmid vectors and anti-IgE strategies with monoclonal antibodies are showing promise.

Genetic immunization: a new era in vaccines and immune therapeutics.

DNA inoculation represents a novel approach to vaccine and immune therapeutic development. The direct injection of gene expression cassettes into a living host transforms a number of cells into factories for production of the introduced gene products. Expression of these delivered genes has important immunological consequences and may result in the specific immune activation of the host against the novel expressed antigens. The recent demonstration by laboratories that these immune responses are protective in some infectious disease experimental models as well as cancers is viewed with cautious optimism. Further, the relatively short development times, ease of large-scale production, low development, manufacturing, and distribution costs all combine with immunological effectiveness to suggest that this technology will dramatically influence the production of a new generation of experimental vaccines and immune therapies. It is hoped that DNA inoculation will ultimately lead to new vaccines that are immunologically effective and economically accessible to all nations.

DNA immunization.

DNA immunization has recently emerged as a highly promising approach for the prevention and therapy of a wide range of infectious and non-infectious diseases. Here, we review the rapid development of this field and recent advances in our understanding of some of the mechanisms by which DNA vaccines stimulate the immune system.