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Molecular Vaccines against Pathogens in the Post-Genomic Era

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The implementation of vaccines has significantly improved human and animal health worldwide, representing the most cost-effective medical intervention in history. Vaccination not only has a major impact on morbidity and mortality for those that received the immunization, but community protection by reducing ...

The implementation of vaccines has significantly improved human and animal health worldwide, representing the most cost-effective medical intervention in history. Vaccination not only has a major impact on morbidity and mortality for those that received the immunization, but community protection by reducing the spread of communicable diseases. Although vaccines mainly target infectious agents, we cannot rule out their potential to control non-transmissible diseases such as cancer, obesity, neurodegenerative disorders and several addictions. It is therefore highly relevant to achieve a broad understanding of the immune responses and the molecular mechanisms involved in the protective efficacy induced by vaccination.

For centuries, diverse historical records have described the human population's efforts to protect themselves against pathogens. The first written evidence of vaccination appears in the 10th century, during the Chinese Song Dynasty, where the procedure of variolization, intentional exposure to the infection using dried scabs from patients with smallpox, was originally described. Edward Jenner in 1798, using the same empirical principle and knowing the risk of variolization, inoculated a child with a preparation derived from a patient that contracted cowpox, inducing immune protection against smallpox. This recorded intervention represents the beginning of the pre-modern era of vaccines. Advances in the field of Microbiology at the end of the 19th century resulted in the development of new vaccines based on killed microorganisms or live attenuated microorganisms, toxoids, and conjugates. These developments along with the advent of Immunology led to the addition of vaccinology as a new scientific discipline.

Systems biology approaches opened a new era in vaccinology. The availability of multi-omic datasets, along with novel bioinformatics tools, offered the opportunity to understand in depth the molecular mechanisms involved in host-pathogen interactions. Comprehensive multi-omic studies using samples collected from vaccinees or individuals exposed to infections have resulted in the characterization of molecular pathways that ultimately can be exploited to potentiate existing or novel vaccines. Similarly, post-genomic information for microorganisms has allowed the in silico identification of essential proteins or virulence factors, which can be selectively chosen to design live attenuated or subunit vaccines by using immunodominant peptides, chimeric proteins or genetic vaccines.

The advances in modern vaccinology have prioritized the development of vaccines against emerging or re-emerging pathogens of global public health concern. However, several vaccine candidates have not shown efficacy in clinical trials, or simply vaccines candidates are not available. The design and implementation of a new generation of vaccines based on the use of a variety of novel platforms, leading to the development of effective synthetic candidates is highly desirable.

This Research Topic covers nucleic acid-based vaccines, structural vaccinology, bivalent or multivalent-protein vaccines, peptide-based vaccines, glycoconjugate-based vaccines and genetically modified microorganisms. Hence we aim to address a major concern in the field that was summarized by von Bufnoff in two sentences “What happened in the past is that most vaccines have been made empirically without a real immunologic rationale” and “We really don't know how to make vaccines in a predictable way. It's still a little bit of black magic.”


Keywords: Structural Vaccinology, Peptide-Based Vaccines, Glycoconjugate, Nucleic Acid-Based Vaccine


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