In silico design of knowledge-based Plasmodium falciparum epitope ensemble vaccines

Malaria is a global health burden, and a major cause of mortality and morbidity in Africa. Here we designed a putative malaria epitope ensemble vaccine by selecting an optimal set of pathogen epitopes. From the IEDB database, 584 experimentally-verified CD8+ epitopes and 483 experimentally-verified CD4+ epitopes were collected; 89% of which were found in 8 proteins. Using the PVS server, highly conserved epitopes were identified from variability analysis of multiple alignments of Plasmodium falciparum protein sequences. The allele-dependent binding of epitopes was then assessed using IEDB analysis tools, from which the population protection coverage of single and combined epitopes was estimated. Ten conserved epitopes from four well-studied antigens were found to have a coverage of 97.9% of the world population: 7 CD8+ T cell epitopes (LLMDCSGSI, FLIFFDLFLV, LLACAGLAYK, TPYAGEPAPF, LLACAGLAY, SLKKNSRSL, and NEVVVKEEY) and 3 CD4+ T cell epitopes (MRKLAILSVSSFLFV, KSKYKLATSVLAGLL and GLAYKFVVPGAATPYE). The addition of four heteroclitic peptides − single point mutated epitopes − increased HLA binding affinity and raised the predicted world population coverage above 99%

In silico design of Mycobacterium tuberculosis epitope ensemble vaccines

Effective control of Mycobacterium tuberculosis is a global necessity. In 2015, tuberculosis (TB) caused more deaths than HIV. Considering the increasing prevalence of multi-drug resistant forms of M. tuberculosis, the need for effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine is Bacillus Calmette-Guérin (BCG). Yet, BCG has many drawbacks limiting its efficacy and applicability. We applied advanced computational procedures to derive a universal TB vaccine and one targeting East Africa. Our approach selects an optimal set of highly conserved, experimentally validated epitopes, with high projected population coverage (PPC). Through rigorous data analysis, five different potential vaccine combinations were selected each with PPC above 80% for East Africa and above 90% for the World. Two potential vaccines only contained CD8+ epitopes, while the others included both CD4+ and CD8+ epitopes. Our prime vaccine candidate was a putative seven-epitope ensemble comprising: SRGWSLIKSVRLGNA, KPRIITLTMNPALDI, AAHKGLMNIALAISA, FPAGGSTGSL, MLLAVTVSL, QSSFYSDW and KMRCGAPRY, with a 97.4% global PPC and a 92.7% East African PPC

Towards the knowledge-based design of universal influenza epitope ensemble vaccines

Motivation: Influenza A viral heterogeneity remains a significant threat due to unpredictable antigenic drift in seasonal influenza and antigenic shifts caused by the emergence of novel subtypes. Annual review of multivalent influenza vaccines targets strains of influenza A and B likely to be predominant in future influenza seasons. This does not induce broad, cross protective immunity against emergent subtypes. Better strategies are needed to prevent future pandemics. Cross-protection can be achieved by activating CD8+ and CD4+ T cells against highly-conserved regions of the influenza genome. We combine available experimental data with informatics-based immunological predictions to help design vaccines potentially able to induce cross-protective T-cells against multiple influenza subtypes. Results: To exemplify our approach we designed two epitope ensemble vaccines comprising highly-conserved and experimentally-verified immunogenic influenza A epitopes as putative non-seasonal influenza vaccines; one specifically targets the US population and the other is a universal vaccine. The USA-specific vaccine comprised 6 CD8+ T cell epitopes (GILGFVFTL, FMYSDFHFI, GMDPRMCSL, SVKEKDMTK, FYIQMCTEL, DTVNRTHQY) and 3 CD4+ epitopes (KGILGFVFTLTVPSE, EYIMKGVYINTALLN, ILGFVFTLTVPSERG). The universal vaccine comprised 8 CD8+ epitopes: (FMYSDFHFI, GILGFVFTL, ILRGSVAHK, FYIQMCTEL, ILKGKFQTA, YYLEKANKI, VSDGGPNLY, YSHGTGTGY) and the same 3 CD4+ epitopes. Our USA-specific vaccine has a population protection coverage (portion of the population potentially responsive to one or more component epitopes of the vaccine, PPC) of over 96% and 95% coverage of observed influenza subtypes. The universal vaccine has a PPC value of over 97% and 88% coverage of observed subtypes

Rosen's (M,R) system as an X-machine

Robert Rosen's (M,R) system is an abstract biological network architecture that is allegedly both irreducible to sub-models of its component states and non-computable on a Turing machine. (M,R) stands as an obstacle to both reductionist and mechanistic presentations of systems biology, principally due to its self-referential structure. If (M,R) has the properties claimed for it, computational systems biology will not be possible, or at best will be a science of approximate simulations rather than accurate models. Several attempts have been made, at both empirical and theoretical levels, to disprove this assertion by instantiating (M,R) in software architectures. So far, these efforts have been inconclusive. In this paper, we attempt to demonstrate why - by showing how both finite state machine and stream X-machine formal architectures fail to capture the self-referential requirements of (M,R). We then show that a solution may be found in communicating X-machines, which remove self-reference using parallel computation, and then synthesize such machine architectures with object-orientation to create a formal basis for future software instantiations of (M,R) systems

ICTV Virus Taxonomy Profile: Herpesviridae 2021

Members of the family Herpesviridae have enveloped, spherical virions with characteristic complex structures consisting of symmetrical and non-symmetrical components. The linear, double-stranded DNA genomes of 125–241 kbp contain 70–170 genes, of which 43 have been inherited from an ancestral herpesvirus. In general, herpesviruses have coevolved with and are highly adapted to their hosts, which comprise many mammalian, avian and reptilian species. Following primary infection, they are able to establish lifelong latent infection, during which there is limited viral gene expression. Severe disease is usually observed only in the foetus, the very young, the immunocompromised or following infection of an alternative host. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Herpesviridae, which is available at ictv.global/report/herpesviridae

Sequence Variation in Multidrug-Ressitant Plasmid pLUH01, Isolated from Human Nasopharyngeal Swabs

Three variants of the multidrug-resistant plasmid pLUH01 were assembled by deep sequencing from nasopharyngeal swabs. All have a 21-bp deletion in the RS14515 hypothetical gene. Variants 1 through 3 have 2, 6, and 3 nucleotide substitutions, respectively, compared to the pLUH01 reference genome. We named the new plasmid variants pLUH01/Lancaster/2015/1 to pLUH01/Lancaster/2015/3

Reassortment of Ancient Neuraminidase and Recent Hemagglutinin in Pandemic (H1N1) 2009 Virus

Sequence analyses show that the outbreak of pandemic (H1N1) 2009 resulted from the spread of a recently derived hemagglutinin through a population of ancient and more diverse neuraminidase segments. This pattern implies reassortment and suggests that the novel form of hemagglutinin conferred a selective advantage

Genome Sequence of Human Papillomavirus 23 Strain HPV-23/Lancaster/2015

The genome of human papillomavirus type 23 (HPV-23; family Papillomaviridae, genus Betapapillomavirus, species Betapapillomavirus 2, type 23) was assembled by deep sequencing from nasopharyngeal swabs. The assembled genome is 2.7% divergent over its full length from the single complete genome of HPV-23 in GenBank (accession no. U31781). We named the strain HPV-23/Lancaster/201

Genome Sequence of Human Rhinovirus A22, Strain Lancaster/2015

The genome of human rhinovirus A22 (HRV-A22) was assembled by deep sequencing RNA samples from nasopharyngeal swabs. The assembled genome is 8.7% divergent from the HRV-A22 reference strain over its full length, and it is only the second full-length genome sequence for HRV-A22. The new strain is designated strain HRV-A22/Lancaster/2015