Infection, Genetics and Evolution

Emerging variants of SARS-CoV-2 with better immune escape mechanisms and higher transmissibility remains a persistent threat across the globe. B.1.617.2 (Delta) variant was first emerged from Maharashtra, India in December, 2020. This variant is classified to be a major cause and concern of the second wave of COVID-19 in India. In the present study, we explored the genomic and structural basis of this variant through computational analysis, protein modelling and molecular dynamics (MD) simulations approach. B.1.617.2 variant carried E156G and Arg158, Phe-157/del mutations in NTD of spike protein. These mutations in N-terminal domain (NTD) of spike protein of B.1.617.2 variant revealed more rigidity and reduced flexibility compared to spike protein of Wuhan isolate. Further, docking and MD simulation study with 4A8 monoclonal antibody which was reported to bind NTD of spike protein suggested reduced binding of B.1.617.2 spike protein compared to that of spike protein of Wuhan isolate. The results of the present study demonstrate the possible case of immune escape and thereby fitness advantage of the new variant and further warrants demonstration through experimental evidence. Our study identified the probable mechanism through which B.1.617.2 variant is more pathogenically evolved with higher transmissibility as compared to the wild-type. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=93 SRC="FIGDIR/small/447321v3_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@b92cborg.highwire.dtl.DTLVardef@1d261f7org.highwire.dtl.DTLVardef@11da73eorg.highwire.dtl.DTLVardef@1cef6ca_HPS_FORMAT_FIGEXP M_FIG C_FIG

Malaria caused by Plasmodium spp. leads to significant morbidity and mortality, particularly in Sub-Saharan African countries with Plasmodium falciparum being the predominant infectious species. The pathogenesis of P. falciparum depends on multiple host and parasitic factors, one of which is the evasion of host immune response due to antigenic variability during the blood stage of infection. The understudied infected erythrocyte expressed protein families STEVOR and RIFIN characterize with antigenic hypervariability and are associated with clinical outcome of the infection and protective acquired immunity based on their topology and localization. We have used two molecular tag methods for successful expression of members of STEVOR and RIFIN protein families as recombinant proteins in E. coli expression system. We have further established the antigenicity of those recombinants and have used Ugandan cohort samples with various P. falciparum infectious status and have compared the seropositivity rate to those recombinants in different age groups against already established short- and long-term markers of infection. We have demonstrated age-dependent immunity acquisition against the tested recombinants, and we have suggested the potential use of STEVOR and RIFIN recombinants as novel markers of P. falciparum infection in serosurveillance. Due to the hypervariability of those protein members we propose that further, more extensive research using a library of expressed variants is needed to strengthen the conclusions made in this study.

The mutations are the key mechanisms responsible for virus survival and its fitness in the host. This process of mutation is implicated in the development of pathogenesis of the dengue viral disease. We report that, all the four serotypes were found to be circulating in Kerala sate of India. Serotypes 1 and 3 were the predominant type (33.3 %) compared to others. The prevalence of co-infection of serotype 1 and 4 was the highest percentage (11.1 %) compared to serotype 2 and serotype 3 (5.5 %). We further highlighted the immunopathological mechanisms of antibody neutralization, CD4+ T cell response and antibody dependent enhancements (ADE) for the possible cause of disease severity in coinfections. Serotype-1 does not show much variations from the previously reported strains from various regions of India. However, serotype-2 showed variations in the sequences from the other strains of serotype-2 previously reported from various regions of India and formed a distinct clade in the genotype-4. Serotype-3 and serotype-4 showed similarity with previously reported strains from India. Moreover, serotype-1 was grouping in genotype-5. Importantly, the serotype-2 grouped with genoptype-4 but exist separately. Serotype-3 was found to be grouped with the genotype-3. The serotype-4 show the very much similarities from the genotype-1 and shows little difference from the previously reported strains from India. Further, mutation in DENV-3 sequences, at position 235 (C to T) and 322 (G to T) shows an important phenomenon which might be adopted by the virus to survive. As severe dengue is linked with the serotype-2, the genetic variations in this serotype points towards the much specific strategy to be adopted in near future to manage the severe dengue disease. In conclusion, we can say that, genetic diversity in the CprM region is present in the different serotypes circulating in the patients from Kerala India and this information may help in the management of dengue viral disease.

Nipah virus (NiV) is a re-emerging zoonotic virus belonging to the Paramyxoviridae family that results in significant neurological damage and raises fatality rates. NiV is classified as a stage III pathogen with a high likelihood of transmission to humans, causing outbreaks intermittently and without any predictable pattern. In Bangladesh, outbreaks of NiV have happened every year since 2001. Even though the disease is severe, no antiviral medications exist for NiV infections. As a consequence, developing a vaccine is crucial. The present research aims to predict an effective epitope-based vaccine by applying immunoinformatic techniques against the fusion and glycoprotein of the Nipah virus. Fusion and glycoproteins were obtained from the UniProt protein database and screened for the T and B cell epitopes using the IEDB and ABCpred servers. Moreover, the constructed 3D structure of the NiV vaccine was occupied with Toll-like receptor 4 for molecular docking and dynamic (MD) simulation studies. Finally, the vaccine design was validated for expression in the PET28a (+) vector of Escherichia coli, and immunological simulations were also conducted. After determination of the allergenicity, antigenicity, and toxicity, the non-allergenic, nontoxic, antigenic, and immunogenic epitopes were used to construct the vaccine with adjuvants and an appropriate linker, including AAY, GPGPG, and KK. The constructed NiV vaccine was confirmed based on its physicochemical properties and docking scores for further analysis. The MD simulations indicated a stabilized structure and increased duration of epitope visibility, indicating strong immune responses. Furthermore, codon optimization and in silico cloning were used to verify bacterial expression of the developed NiV vaccine in E. coli. The results showed that NiV can increase immune responses against the Nipah virus. Furthermore, in vitro and in vivo research and clinical studies are recommended to establish the findings of this study.

Mutations primarily in the Spike (S) gene resulted in the emergence of many SARS-CoV-2 variants like Alpha, Beta, Delta and Omicron variants. This has also caused a number of COVID-19 pandemic waves which have impacted human lives in different ways due to restriction measures put in place to curb the spread of the virus. In this study, evolutionary patterns found in SARS-CoV-2 sequences of samples collected from Zimbabwean COVID-19 patients were investigated. High coverage SARS-CoV-2 whole genome sequences were downloaded from the GISAID database along with the GISAID S gene reference sequence. Biopython, NumPy and Pandas Data Science packages were used to load, slice and clean whole genome sequences outputting a fasta file with approximate Spike (S) gene sequences. Alignment of sliced dataset with GISAID reference sequence was done using Jalview 2.11.1.3 to find exact sequences of SARS-CoV-2 S gene. Evidence of recombination signals was investigated using RDP 4.1 and pervasive selection in the S gene was investigated using FUBAR algorithm hosted on the Datamonkey webserver. Matplotlib and Seaborn Python packages were used for Data Visualisation. A plot of Bayes factor hypothesizing non-synonymous substitution being greater than synonymous substitution ({beta} > ) in the S protein sites showed 3 peaks with evidence of strong divergence. These 3 diverging S protein sites were found to be D142G, D614G and P681R. No evidence of recombination was detected by 9 methods of RDP which use different approaches to detect recombination signals. This study is useful in guiding drug, vaccine and diagnostic innovations toward better control of the pandemic. Additionally, this study can guide other non-biological interventions as we better understand the changes in various viral characteristics driven by the observed evolutionary patterns.

The whole world is drastically affected by the current pandemic due to severe virus, SARS-CoV-2 and scientists are rigorously looking for the efficient vaccine against it that become an emergent issue. Reverse vaccinology approach may provide us with significant therapeutic leads in this direction and further determination of T-cell / B-cell response to antigen. In the present study, we conducted population coverage analysis referring to the diverse Indian population. By using tools from Immune epitope database (IEDB), HLA- distribution analysis was performed to find the most promiscuous T-cell epitope out of In silico determined epitope of Spike protein from SARS-CoV-2. Selection of these epitopes have been conducted based on their binding affinity with the maximum number of HLA alleles belong to the highest population coverage rate values for the chosen geographical area in India. 404 cleavage sites within the 1288 amino acids sequence of spike glycoprotein were determined by NetChop proteasomal cleavage prediction suggesting that this protein has adequate sites in the protein sequence for cleaving into appropriate epitopes. For population coverage analysis, 221 selected epitopes are considered that shows the projected population coverage as 83.08% with 19.29 average hit (average number of epitope hits/HLA combinations recognized by the population) and 5.91 pc90 (minimum number of epitope hits/HLA combinations recognized by 90% of the population). 54 epitopes are found with the highest coverage among the Indian population and highly conserved within the given spike RBD domain sequence. Docking analysis of each epitope with their respective allele suggests that the epitope NSFTRGVYY represents highest binding affinity with docking score -7.6 kcal/mol with its allele HLA-C*07:01 among all the epitopes. Since the Covid-19 cases are still in progress and seem to remain like this until we find an effective vaccine, moreover in countries like India, vast diversity in the population may present a hindrance to particular vaccine efficiency. Outcomes from this study could be critical to design vaccine against SARS-CoV-2 for a different set of the population within the country.

The molecular hitchhiking model proposes that linked non-coding regions also undergo fixation, while fixing a beneficial allele in a population. This concept can be applied to identify loci with functional and evolutionary significance. Putative circumsporozoite protein (CSP) in Plasmodium vivax (PvpuCSP) identified following the molecular hitchhiking model, holds evolutionary significance. We investigated the extent of genetic polymorphism in PvpuCSP and the role of natural selection which shapes the genetic composition and maintains the diversity in P. vivax isolates from India. Sequencing the putative CSP of P. vivax (PvpuCSP) in 71 isolates revealed a well-conserved N- and C-terminal, constituting around 80% of the gene. PCR amplification and sequencing validated extensive diversity in the repeat region, ranging from 1.8 to 2.2 kb towards the C-terminal, identifying 37 different alleles from 71 samples. The recent and exclusive accumulation of repeats in puCSP within P. vivax highlights its highly variable length polymorphism, making it a potential marker for estimating diversity and infection complexity. Episodic diversifying selection in the PvpuCSP repeat region, evidenced by statistically significant p-values and likelihood ratios, enhances amino acid diversity at various phylogenetic levels, facilitating adaptation for accommodating different substrates for degradation.

In this work, we evaluated the levels of genetic diversity in 95 genomes of the carriers of the Omicron B.1.1.529 mutation in SARS-CoV-2 from South Africa, Asia, Massachusetts-USA, Rhode Island-USA, United Kingdom and Germany. All with 29,996pb extension and recovered from GENBANK and publicly available at the National Center for Biotechnology and Information (NCBI). All gaps and conserved sites were extracted for the construction of a phylogenetic tree and for specific methodologies of estimates of paired FST, Molecular Variance (AMOVA), Genetic Distance, Incompatibility, demographic expansion analyses, molecular diversity and of evolutionary divergence time analyses, always with 20,000 random permutations. The results revealed the presence of only 75 parsimony-informative sites, sites among the 29,996bp analyzed. The analyses based on FST values, confirmed the absence of distinct genetic structuring with fixation index of 98% and with a greater component of population variation (6%) for a "p" 0.05. Tau variations (related to the ancestry of the groups), did not reveal significant moments of divergence, supported by the incompatible analysis of the observed distribution ({tau} = 0%). It is safe to say that the large number of existing polymorphisms reflects major changes in the protein products of viral populations in all countries and especially In South Africa. This consideration provides the safety that, because there are large differences between the haplotypes studied, these differences are minimal within the populations analyzed geographically and, therefore, it does not seem safe to extrapolate the results of polymorphism and molecular diversity levels found in the Variant Omicron B.1.529 of SARS-CoV-2 for wild genomes or other mutants. This warns us that, due to their higher transmission speed and infection, possible problems of molecular adjustments in vaccines already in use may be necessary in the near future.

BackgroundOn May 7, 2022, a case of monkeypox virus (MPXV) has been reported to the WHO. It causes a viral zoonotic disease with characteristics comparable to that of smallpox cases. Monkeypox could be a serious health concern as it is already spreading to multiple countries worldwide. To prevent the monkeypox infection and for its early detection, a potential vaccine and diagnostic candidate is urgently required. MethodIn present study we have used different in silico methods to screen the entire genome with its approximately 191 genes for potential epitopes present in proliferation and virulent proteins of monkeypox virus. All protein sequences were retrieved from different genomic and proteome databases listed in Uniprot or NCBI. ResultsIn the present study we have screened potential epitopes from 11 different proteins of Monkeypox. All the included protein play an important role in pathogenesis and/or proliferation of Monkeypox virus. We have identified in total 984 CTL and 168 HTL epitopes with highest score in our epitope screening. The reported epitopes could be potential candidates for the design of an early detection diagnostic kit specific for the monkeypox virus. Out of these target peptides we have included a total of 39 CTL epitopes and 39 HTL epitopes in design of multi-epitope vaccine candidates. These shortlisted epitopes are highly conserved amongst different strains and origin of monkeypox viruses. The population coverage by joint administration of CTL and HTL MEVs is predicted to be high with the epitopes showing potential to bind upto 24 different CTL and HTL HLA allele molecules. The epitopes used in MEVs are examined to be highly immunogenic, non allergic but antigenic, and non toxic. All the CTL and HTL MEVs designed utilizing the epitopes have physiochemical properties favor its over expression in human cells. The optimized cDNA constructs of CTL and HTL MEVs also favor over expression of MEVs in human cells. Overall, the MEV construct proposed by us are fissile for expression in the lab and for further in vivo studies. ConclusionControl and fight against emerging diseases such as MPXV requires pathogen diagnostic and novel vaccine approaches. We screened for several epitopes and designed a MEV providing a potential solution for both purposes. Our method allows rapid screening and provides a rational strategy for the development of vaccine candidate effective in fighting MPXV and other unexpected upcoming diseases.

The challenges imposed by the ongoing outbreak of severe acute respiratory syndrome coronavirus-2 affects every aspect of our modern world, ranging from our health to our socio-economic needs. Our existence highly depends on the vaccines availability, which demands in-depth research of the available strains and their mutations. In this work, we have analyzed all the available SERS-CoV2 genomes isolated from the Kingdom of Bahrain in terms of their variance and origin analysis. We have predicted various known and unique mutations in the SERS-CoV2 isolated from Bahrain. The complexity of the phylogenetic tree and dot plot representation of the strains mentioned above with other isolates of Asia indicates the versatility and multiple origins of Bahrains SERS-CoV2 isolates. We have also identified two high impact spike mutations from these strains which increase the virulence of SARS-CoV2. Our research could have a high impact on vaccine development and distinguishes the source of SERS-CoV2 in the Kingdom of Bahrain.

In this work, we evaluated the levels of genetic diversity in 38 complete genomes of SARS-CoV-2 from five Central American countries (Belize, Guatemala, Cuba, Jamaica and Puerto Rico) with 04, 10, 2, 8 and 14 haplotypes, respectively, with an extension of up to 29,885 bp. All sequences were publicly available on the National Biotechnology Information Center (NCBI) platform. Using specific methodologies for paired FST, AMOVA, mismatch, demographic-spatial expansion, molecular diversity and for the time of evolutionary divergence, it was possible to notice that only 79 sites remained conserved and that the high number of polymorphisms found helped to establish a clear pattern of genetic non-structuring, based on the time of divergence between the groups. The analyses also showed that significant evolutionary divergences within and between the five countries corroborate the fact that possible rapid and silent mutations are responsible for the increase in genetic variability of the Virus, a fact that would hinder the work with molecular targets for vaccines and medications in general.

BackgroundNipah virus (NiV) is an emerging zoonotic virus that caused several serious outbreaks in the South Asian region with high mortality rates ranging from 40 to 90% since 2001. NiV infection causes lethal encephalitis and respiratory disease with the symptom of endothelial cell-cell fusion. No specific vaccine has yet been reported against NiV. Methodology and Principal FindingsRecently, the design of some Multi-Epitope Vaccines (MEV) has been proposed but that involves vary limited number of epitopes which limits the potential of vaccine. To address the urgent need for a specific and effective vaccine against NiV infection, in the present study, we have designed two MEVs composed of 33 Cytotoxic T lymphocyte (CTL) epitopes and 38 Helper T lymphocyte (HTL) epitopes. Both the MEVs carry potential B cell linear epitope overlapping regions, B cell discontinuous epitopes as well as IFN-{gamma} inducing epitopes. Hence the designed MEVs carry potential to elicit cell-mediated as well as humoral immune response. Selected CTL and HTL epitopes were validated for their stable molecular interactions with HLA class I and II alleles as well as in case of CTL epitopes, with human transporter associated with antigen processing (TAP). Human {beta}-defensin 2 and {beta}-defensin 3 were used as adjuvants to enhance the immune response of both the MEVs. Molecular dynamics simulation studies of MEVs-TLR3 ectodomain (Toll-Like Receptor 3) complex indicate the stable molecular interaction. Further, the codon optimized cDNA of both the MEVs has shown high expression potential in the mammalian host cell line (Human). Hence for further studies, the designed MEV constructs could be expressed and tried in-vivo as potential vaccine candidates against NiV. ConclusionWe conclude that the MEVs designed and in silico validated here could be highly potential vaccine candidate to combat NiV, with greater effectiveness, high specificity and large human population coverage worldwide. AUTHOR SUMMARYNipah Virus (NiV) has caused several outbreaks in past two decades calming large number of human lives. Our present work aims to design and in silico validate Multi-Epitope Vaccine against NiV. The current approach to design vaccine involves whole virus or full length proteins as vaccine candidates against NiV. These approaches carry chances of raising the unwanted non-neutralizing antibodies which have been found to cause clinical complexities. Recently few Multi-Epitope vaccines have also been proposed, but they have involved limited number of epitopes for vaccine design in result limiting the effectiveness and human population coverage. Here in our MEVs we have involved all the proteins of NiV to design the vaccine. Moreover since we have used in silico validated epitopes we may conclude that the here proposed MEVs would be highly specific, effective and potential vaccine candidate to combat NiV with large human population coverage worldwide.

Genomic mutation of the virus may impact the viral adaptation to the local environment, their transmission, disease manifestation, and the effectiveness of existing treatment and vaccination. The objectives of this study were to characterize genomic variations, non-synonymous amino acid substitutions, especially in target proteins, mutation events per samples, mutation rate, and overall scenario of coronaviruses across the country. To investigate the genetic diversity, a total of 184 genomes of virus strains sampled from different divisions of Bangladesh with sampling dates between the 10th of May 2020 and the 27th of June 2020 were analyzed. To date, a total of 634 mutations located along the entire genome resulting in non-synonymous 274 amino acid substitutions in 22 different proteins were detected with nucleotide mutation rate estimated to be 23.715 substitutions per year. The highest non-synonymous amino acid substitutions were observed at 48 different positions of the papain-like protease (nsp3). Although no mutations were found in nsp7, nsp9, nsp10, and nsp11, yet orf1ab accounts for 56% of total mutations. Among the structural proteins, the highest non-synonymous amino acid substitution (at 36 positions) observed in spike proteins, in which 9 unique locations were detected relative to the global strains, including 516E>Q in the boundary of the ACE2 binding region. The most dominated variant G614 (95%) based in spike protein is circulating across the country with co-evolving other variants including L323 (94%) in RNA dependent RNA polymerase (RdRp), K203 (82%) and R204 (82%) in nucleocapsid, and F120 (78%) in NSP2. These variants are mostly seen as linked mutations and are part of a haplotype observed in Europe. Data suggest effective containment of clade G strains (4.8%) with sub-clusters GR 82.4%, and GH clade 6.4%. HighlightsO_LIWe have sequenced 137 and analyzed 184 whole-genomes sequences of SARS-CoV-2 strains from different divisions of Bangladesh. C_LIO_LIA total of 634 mutation sites across the SARS-CoV-2 genome and 274 non-synonymous amino acid substitutions were detected. C_LIO_LIThe mutation rate of SARS-CoV-2 estimated to be 23.715 nucleotide substitutions per year. C_LIO_LINine unique variants were detected based on non-anonymous amino acid substitutions in spike protein relative to the global SARS-CoV-2 strains. C_LI

SARS-CoV-2 has rapidly transmitted worldwide and results in the COVID-19 pandemic. Spike glycoprotein on surface is a key factor of viral transmission, and has appeared a lot of variants due to gene mutations, which may influence the viral antigenicity and vaccine efficacy. Here, we used bioinformatic tools to analyze B-cell epitopes of prototype S protein and its 9 common variants. 12 potential linear and 53 discontinuous epitopes of B-cells were predicted from the S protein prototype. Importantly, by comparing the epitope alterations between prototype and variants, we demonstrate that B-cell epitopes and antigenicity of 9 variants appear significantly different alterations. The dominant D614G variant impacts the potential epitope least, only with moderately elevated antigenicity, while the epitopes and antigenicity of some mutants(V483A, V367F, etc.) with small incidence in the population change greatly. These results suggest that the currently developed vaccines should be valid for a majority of SARS-CoV-2 infectors. This study provides a scientific basis for large-scale application of SARS-CoV-2 vaccines and for taking precautions against the probable appearance of antigen escape induced by genetic variation after vaccination. Author SummaryThe global pandemic of SARS-CoV-2 has lasted for more than half a year and has not yet been contained. Until now there is no effective treatment for SARS-CoV-2 caused disease (COVID-19). Successful vaccine development seems to be the only hope. However, this novel coronavirus belongs to the RNA virus, there is a high mutation rate in the genome, and these mutations often locate on the Spike proteins of virus, the gripper of the virus entering the cells. Vaccination induce the generation of antibodies, which block Spike protein. However, the Spike protein variants may change the recognition and binding of antibodies and make the vaccine ineffective. In this study, we predict neutralizing antibody recognition sites (B cell epitopes) of the prototype S protein of SARS-COV2, along with several common variants using bioinformatics tools. We discovered the variability in antigenicity among the mutants, for instance, in the more widespread D614G variant the change of epitope was least affected, only with slight increase of antigenicity. However, the antigenic epitopes of some mutants change greatly. These results could be of potential importance for future vaccine design and application against SARS-CoV2 variants.

Although Hepatitis E viral illness is usually self-limiting, higher rates of morbidity and mortality are frequently observed during pregnancy in South Asian countries including Bangladesh. Of the four common variants, hepatitis E virus genotype 1 is mainly prevalent in South Asian countries. Pregnant women usually suffer from a state of immunosuppression. It is yet to be known whether virus specific immunoglobulin G (IgG) immune responses have any association with the vulnerability of pregnant women to acute hepatitis with E virus. The study aimed to compare the viral load and IgG responses of hepatitis E-infected pregnant women with that of non-pregnant women with same infection. Real Time -quantitative reverse transcription Polymerase Chain Reaction and Sanger sequencing were performed to determine the viral load and genotype, respectively, whereas Enzyme Linked Immunosorbent Assay method was used to determine hepatitis E virus specific serum IgG antibody index along with IgG avidity index. Although significant negative correlations were observed between log viral copy number and log IgG antibody index in the late acute phases of jaundice for both pregnant (r= -0.7971, p=0.0002) and non-pregnant women (r= -0.9117, p=0.0002), serum log viral copy number of pregnant women was significantly higher than that of the non-pregnant counterpart (p=0.0196) in the late acute stage of jaundice. In addition, log hepatitis E virus IgG antibody index of pregnant women was significantly lower than the non-pregnant women in the late phase of jaundice induced by hepatitis E virus (p=0.0303). Moreover, pregnant women with acute hepatitis E had higher cross-reactive IgG than in the non-pregnant women (p=0.0017). All the patients got infected with hepatitis E virus were in Genotype 1 variety. The study demonstrates that virus-specific poor IgG responses might be responsible for vulnerability of pregnant women to acute hepatitis with hepatitis E virus. Author SummaryAcute hepatitis caused by hepatitis E virus (HEV) Genotype 1 is a public health problem in Asian countries and especially it poses a potential health threat to pregnant women causing 19% to 25% mortality, particularly in South Asian countries including Bangladesh. The study aimed to explore whether HEV IgG immune responses were compromised during pregnancy, which might contribute to higher viral load and disease severity. Accordingly, pregnant and non-pregnant women with acute hepatitis (clinically presented with nausea, loss of appetite and /or jaundice) were enrolled from different tertiary care hospitals in Dhaka city. All these patients were screened and hepatitis E were differentiated from other hepatitis (caused by A, B, C) using Enzyme Linked Immunosorbent Assay (ELISA) methods. HEV IgG antibody/avidity indices and viral loads were measured using ELISA and real time quantitative polymerase chain reaction (RT-qPCR), respectively. The study showed that pregnant women with acute hepatitis E had lower IgG indices with higher viral load than their non-pregnant counterpart. Overall, the study revealed that virus-specific poor IgG responses might render pregnant women vulnerable to acute hepatitis E of varying degree of severity which might be associated with higher viral load.

Against the backdrop of the rapid global takeover and dominance of BA.1/BA.2 and subsequently BA.2.86 lineages, the emergence of a highly divergent SARS-CoV-2 variant warrants characterization and close monitoring. Recently, another such BA.2 descendent, designated BA.2.87.1, was detected in South Africa. Here, we show using spike-pseudotyped viruses that BA.2.87.1 is less resistant to neutralisation by prevailing antibody responses in Sweden than other currently circulating variants such as JN.1. Further we show that a monovalent XBB.1.5-adapted booster enhanced neutralising antibody titers to BA.2.87.1 by almost 4-fold. While BA.2.87.1 may not outcompete other currently-circulating lineages, the repeated emergence and transmission of highly diverged variants suggests that another large antigenic shift, similar to the replacement by Omicron, may be likely in the future.

BackgroundThe Monkeypox (Mpox) virus is a zoonotic Orthopoxvirus with a global outbreak that began in 2022 and spread to more than 128 countries, with more than 132,000 confirmed cases and 1500 deaths. The pandemic preparedness pipeline emphasizes the importance of diagnostic surveillance of pathogens in at-risk populations to monitor transmission and mitigate the impact on public health. Unfortunately, the current gold standard diagnostic tool for Mpox is limited in its field applicability. Therefore, there is a crucial need for the development of robust novel diagnostic tools to enable continuous surveillance of the disease. As such, this work sought to design and validate novel multiepitope antigens as diagnostic tools for Mpox serosurveillance. MethodsUsing immunoinformatic approaches, two novel Mpox multiepitope antigens (MP-MEDA-1 and MP-MEDA-2) were designed using linear B-epitopes of viral proteins previously characterized in Mpox serodiagnosis. The 3D structures of the designed antigens were predicted, refined, and validated. Protein-protein docking and interaction analyses were performed between the designed diagnostic antigens and the Fab regions of human IgA, IgG, and IgM. ResultsThe designed antigens were predicted to be antigenic and demonstrated thermostability with desirable physicochemical properties. In addition, both antigens also demonstrated stable interactions with the Fab regions of selected immunoglobulins, with several residues interacting at the interfaces of all the docked complexes. ConclusionsThese preliminary findings highlight the potential of the MP-MEDA-1 and MP-MEDA-2 antigens as candidates to be further characterized for Mpox serosurveillance. The next phase of this project will focus on the expression and serological characterization of both antigens to determine their diagnostic parameters (sensitivity, specificity, and others).

Cetaceans correspond to mammals that have returned to the marine environment. Adaptive changes are very significant with the conversion of the limbs into flippers. It is studied the changes that have occurred in immunoglobulins, MHC class I and II and T cell receptors genes. Constant regions of immunoglobulins are similar to those of the rest of mammals. An exception is the IgD gene, which is composed of three CH domains but CH1 similar to CH1 of immunoglobulin M. In the IGHV locus, it exist a decrease in the number of VH genes with the absence of genes within Clan I. The number of V{lambda} genes is greater than that of V{kappa}. In the genes for T lymphocyte receptors, it exists a decrease in the number of V genes with loss of significant clades and subclades. In V{beta} and V{gamma}, there is also the loss of clades. These declines of V, V{beta} and V{gamma} are not present Artiodactyla, and they are specific to Cetaceans. In MHC present tree evolutive lines of class I genes. These species have DQ, DR, DO and DM genes, but they are no present DP genes.

SARS-CoV-2 is considered a pandemic virus and presents a major strain on public health globally. SARS-CoV-2 infects mammalian cells by binding to its receptor, ACE2 which is mediated by the viral spike glycoprotein, specifically the receptor binding domain (RBD) within the spike protein. Recent development of vaccines against SARS-CoV-2 spike protein are currently the best strategy to reduce morbidity and mortality from infection. Like all viruses, SARS-CoV-2 evolves which may result in mutations which are benign or alter its viral fitness. The evolution of SARS-CoV-2 may increase the virulence, possibly by increasing the infectivity of the virus through strengthening the binding of the RBD to ACE2 or enabling the virus to evade naturally or vaccine induced immune responses. To address the need to characterise the evolution of SARS-CoV-2, this study has compared SARS-CoV2 sequences globally to the Wuhan reference strain at different time points. Additionally, by assigning scores to sequence data, which quantify each sequences binding strength to ACE2 and ability to evade patient derived antibodies, we have demonstrated that over time SARS-CoV-2 has evolved in less than one year to increase its ability to evade antibodies and increase the binding free energy between the RBD and ACE2.

Foot and Mouth Disease Virus has seven distinct, geographically localized, serotypes and a vaccination targeting one serotype does not confer immunity against another serotype. The use of inactivated vaccines is not safe and confers an immunity with a relatively shorter time. Using the VP1 sequences isolated in East Africa, we have predicted epitopes able to induce humoral and cell-mediated immunity in cattle. The Wu-Kabat variability index calculated in this study reflects the variable, including the known GH loop, and conserved regions, with the latter being good candidates for region-tailored vaccine design. Furthermore, we modelled the identified epitopes on a 3D model (PDB ID:5aca) to represent the epitopes structurally. This study can be used for in vitro and in vivo experiments.