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Rocket Science
Published in Norman Begg, The Remarkable Story of Vaccines, 2023
While lab scientists are getting smarter at manipulating genetic material and proteins, computers are starting to play a significant role in vaccine development. During the 1990s, scientists began to sequence the entire genome of microorganisms. Rino Rappuoli, an Italian researcher from Siena, saw the potential for vaccines. A quiet unassuming man, Rino is a giant in the field of vaccine discovery. He invented reverse vaccinology, which uses bioinformatics (the methods and software needed to understand biological data) to design new vaccines. With the entire sequence of a microorganism sitting on a computer, it can be scanned to look for potential components that could go into a vaccine. This is much quicker than the traditional hit or miss approach, where multiple different candidates are produced, in the hope that one succeeds. Rino used this to develop the first successful vaccine against meningococcal group B vaccine. He found over 600 possible component antigens, eventually incorporating the four most common ones into the vaccine. The age of computer-designed vaccines had arrived.
An Introduction to the Immune System and Vaccines
Published in Patricia G. Melloy, Viruses and Society, 2023
The use of sequencing techniques (ways to read the genetic code) and genome-wide analysis has greatly aided the process of finding an antibody that would work to block a pathogen, as well as candidate antigens that might work well in a vaccine. The approach of starting with a candidate structure or sequence first and then testing for the ability to induce an immune response is known as “reverse vaccinology” (Ahmed, Ellis, and Rappuoli 2017). One can examine all the potential antigens of the pathogen first, in a large-scale study, and select which antigens to test for vaccine development. Researchers emphasize that you may not even need to culture the pathogen in the lab with this approach, starting with computational analysis instead and then moving to working with recombinant pathogen proteins for testing in animal models (Del Tordello, Rappuoli, and Delany 2017). In addition, high throughput approaches have been used to identify all the antibodies produced in an immune response, “the antibody repertoire” (Ahmed, Ellis, and Rappuoli 2017). Not only has antibody repertoire analysis been used in vaccine development, but this approach has also been useful in studies of autoimmune diseases. One can identify potential “autoantigens,” which are proteins from one’s own body that are recognized abnormally by the immune system, and also the “autoantibodies” created by the immune system to treat and screen for autoimmune diseases (Robinson 2015).
Computational Biology and Bioinformatics in Anti-SARS-CoV-2 Drug Development
Published in Debmalya Barh, Kenneth Lundstrom, COVID-19, 2022
Although vaccine development has traditionally used the “trial-and-error” approach, computational vaccinology constitutes a promising development that can facilitate vaccine design and speed up this long and costly process. Russo et al. indicated that a combination of AI and systems biology represents a very promising direction for the intelligent anti-COVID-19 vaccine design [194], whereas Hwang et al. emphasized that computational tools have been applied successfully as a part of the reverse vaccinology approach for SARS-CoV-2 vaccine development, where they were used for antigen selection, and epitope, toxicity and allergenicity predictions [195].
4CMenB vaccine and its role in preventing transmission and inducing herd immunity
Published in Expert Review of Vaccines, 2022
Mark McMillan, Helen S Marshall, Peter Richmond
Despite meningococcal B being the predominant group causing disease in many parts of the world, a broad-acting group B vaccine has not been available until relatively recently. Concerns that a group B polysaccharide or conjugate vaccine may induce autoantibodies, or may not be immunogenic, were the main reason for the delayed development [34,35]. Reverse vaccinology is the process of antigen discovery starting from genome information [36]. This process was used to identify antigens that were likely to elicit serum bacterial antibody (SBA) responses to protect against a broad range of invasive group B strains (4CMenB [Bexsero; GSK]). Another recombinant vaccine (MenB-FHbp [Trumenba; Pfizer]) has also been developed using traditional immunologic approaches to identify new antigens capable of eliciting SBA. As recombinant vaccines are developed using different technologies than conjugate meningococcal vaccines, similar herd immunity to that observed following meningococcal A and C vaccination programs cannot be assumed [37,38].
In Vitro Activation of Macrophages by an MHC Class II-restricted Trichomonas Vaginalis TvZIP8-derived Synthetic Peptide
Published in Immunological Investigations, 2022
Victor Ermilo Arana-Argáez, Emanuel Ceballos-Góngora, María Elizbeth Alvarez-Sánchez, Antonio Euan-Canto, Julio Lara-Riegos, Julio César Torres-Romero
It has been described that transmembrane proteins, including transporters and receptors, can be processed by APC and present peptides on their surface via the MHC class II. TvZIP8 has been reported recently as a member of the ZIP transporters present in T. vaginalis which share high homology with other ZIP family members in diverse eukaryotes. However, they exhibited non-conserved regions that represent possible specific epitopes. With the genome-wide screen of an organism for the purpose of identifying potential epitopes in antigens that might be suitable for vaccine development, emerged a new concept called reverse vaccinology (Rappuoli et al. 2016). In this work, we used this strategy to identify putative MHC class II-restricted epitopes from TvZIP8 transporter of T. vaginalis. To our knowledge, this is the first report where potential immunogenic antigens or peptides from sequences of trichomonad proteins can be identified through reverse vaccinology.
Understanding modern-day vaccines: what you need to know
Published in Annals of Medicine, 2018
Volker Vetter, Gülhan Denizer, Leonard R. Friedland, Jyothsna Krishnan, Marla Shapiro
Finally, reverse vaccinology is a new technology in which genes encoding potential antigenic proteins are identified from the entire genome of a given pathogen [41]. The identified proteins are then tested in vitro and in vivo to determine whether they are immunogenic and induce protective antibodies. Reverse vaccinology has been used to develop a vaccine against the challenging Neisseria meningitidis serogroup B [42]. Unlike other N. meningitidis serogroups, serogroup B is covered by capsular polysaccharides that have similarities to human polysaccharides. This property substantially reduces the immunogenicity of these polysaccharides and could, at least theoretically, trigger antibodies against the human host and cause auto-immune diseases [42]. In addition, a vaccine relying on recombinant proteins has been unsuccessful because of the high antigenic variation in circulating strains [42]. Reverse vaccinology helped identify four novel antigenic proteins, which have been combined in a tetravalent meningococcal B vaccine (Bexsero, GSK) [42]. By contrast, a more traditional approach of protein screening was used to develop a bivalent meningococcal B vaccine (Trumenba, Pfizer) [43].