Search Results (11)

Newcastle disease virus (NDV) continues to present a significant challenge for vaccination due to its rapid evolution and the emergence of new variants. Although molecular and sequence data are now quickly and inexpensively produced, genetic distance rarely serves as a good proxy for cross-protection, while experimental studies to assess antigenic differences are time consuming and resource intensive. In response to these challenges, this study explores and compares several machine learning (ML) methods to predict the antigenic distance between NDV strains as determined by hemagglutination-inhibition (HI) assays. By analyzing F and HN gene sequences alongside corresponding amino acid features, we developed predictive models aimed at estimating antigenic distances. Among the models evaluated, the random forest (RF) approach outperformed traditional linear models, achieving a predictive accuracy with an R² value of 0.723 compared to only 0.051 for linear models based on genetic distance alone. This significant improvement demonstrates the usefulness of applying flexible ML approaches as a rapid and reliable tool for vaccine selection, minimizing the need for labor-intensive experimental trials. Moreover, the flexibility of this ML framework holds promise for application to other infectious diseases in both animals and humans, particularly in scenarios where rapid response and ethical constraints limit conventional experimental approaches. Full article

Adeno-associated viruses (AAVs) are non-pathogenic, replication-deficient viruses that have gained widespread attention for their application as gene therapy vectors. While these vectors offer high transduction efficiency and long-term gene expression, the host immune response poses a significant challenge to their clinical success. This review focuses on the obstacles to evaluating the humoral response to AAVs. We discuss the problems with the validation of in vitro tests and the possible approaches to overcome them. Using published data on neutralizing titers of AAV serotypes, we built the first antigenic maps of AAVs in order to visualize the antigenic relationships between varying serotypes. Full article

The emergence of SARS-CoV-2 variants escaping immunity challenges the efficacy of current vaccines. Here, we investigated humoral recall responses and vaccine-mediated protection in Syrian hamsters immunized with the third-generation Comirnaty^® Omicron XBB.1.5-adapted COVID-19 mRNA vaccine, followed by infection with either antigenically closely (EG.5.1) or distantly related (JN.1) Omicron subvariants. Vaccination with the YF17D vector encoding a modified Gamma spike (YF-S0*) served as a control for SARS-CoV-2 immunity restricted to pre-Omicron variants. Our results show that both Comirnaty^® XBB.1.5 and YF-S0* induce robust, however, poorly cross-reactive, neutralizing antibody (nAb) responses. In either case, total antibody and nAb levels increased following infection. Intriguingly, the specificity of these boosted nAbs did not match the respective challenge virus, but was skewed towards the primary antigen used for immunization, suggesting a marked impact of antigenic imprinting, confirmed by antigenic cartography. Furthermore, limited cross-reactivity and rapid decline in nAbs induced by Comirnaty^® XBB.1.5 with EG.5.1 and, more concerning, JN.1, raises doubts about sustained vaccine efficacy against recent circulating Omicron subvariants. In conclusion, we demonstrate that antigenic imprinting plays a dominant role in shaping humoral immunity against emerging SARS-CoV-2 variants. Future vaccine design may have to address two major issues: (i) overcoming original antigenic sin that limits the breadth of a protective response towards emerging variants, and (ii) achieving sustained immunity that lasts for at least one season. Full article

The H5 subtype highly pathogenic avian influenza viruses bearing the clade 2.3.4.4 HA gene have been pervasive among domestic poultry and wild birds worldwide since 2014, presenting substantial risks to human and animal health. Continued circulation of clade 2.3.4.4 viruses has resulted in the emergence of eight subclades (2.3.4.4a–h) and multiple distinct antigenic groups. However, the key antigenic substitutions responsible for the antigenic change of these viruses remain unknown. In this study, we analyzed the HA gene sequences of 5713 clade 2.3.4.4 viruses obtained from a public database and found that 23 amino acid residues were highly variable among these strains. We then generated a series of single-amino-acid mutants based on the H5-Re8 (a vaccine seed virus) background and tested their reactivity with a panel of eight monoclonal antibodies (mAbs). Six mutants bearing amino acid substitutions at positions 120, 126, 141, 156, 185, or 189 (H5 numbering) led to reduced or lost reactivity to these mAbs. Further antigenic cartography analysis revealed that the amino acid residues at positions 126, 156, and 189 acted as immunodominant epitopes of H5 viruses. Collectively, our findings offer valuable guidance for the surveillance and early detection of emerging antigenic variants. Full article

Swine influenza is a respiratory disease that affects the pork industry and is a public health threat. It is caused by type A influenza virus (FLUAV), which continuously undergoes genetic and antigenic variations. A large amount of information regarding FLUAV in pigs is available worldwide, but it is limited in Latin America. The HA sequences of H1 subtype FLUAV-positive samples obtained from pigs in Colombia between 2008–2021 were analyzed using sequence-based antigenic cartography and N-Glycosylation analyses. Of the 12 predicted global antigenic groups, Colombia contained five: four corresponding to pandemic strains and one to the classical swine H1N1 clade. Circulation of these clusters was observed in some regions during specific years. Ca2 was the immunodominant epitope among Colombian viruses. The counts of N-Glycosylation motifs were associated with the antigenic cluster ranging from three to five. The results show for the first time the existence of antigenic diversity of FLUAV in Colombia and highlight the impact of spatial and temporal factors on this diversity. This study provides information about FLUAV variability in pigs under natural conditions in the absence of vaccination and emphasizes the need for surveillance of its phylogenetic and antigenic characteristics. Full article

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infects many mammals, and SARS-CoV-2 circulation in nonhuman animals may increase the risk of novel variant emergence. Cats are highly susceptible to SARS-CoV-2 infection, and there were cases of virus transmission between cats and humans. The objective of this study was to assess the prevalence of SARS-CoV-2 variant infection of cats in an urban setting. We investigated the prevalence of SARS-CoV-2 variant infections in domestic and community cats in the city of Pittsburgh (n = 272). While no cats tested positive for SARS-CoV-2 viral RNA, 35 cats (12.86%) tested SARS-CoV-2-antibody-positive. Further, we compared a cat-specific experimental lateral flow assay (eLFA) and species-agnostic surrogate virus neutralization assay (sVNT) for SARS-CoV-2 antibody detection in cats (n = 71). The eLFA demonstrated 100% specificity compared to sVNT. The eLFA also showed 100% sensitivity for sera with >90% inhibition and 63.63% sensitivity for sera with 40–89% inhibition in sVNT. Using a variant-specific pseudovirus neutralization assay (pVNT) and antigen cartography, we found the presence of antibodies to pre-Omicron and Omicron SARS-CoV-2 variants. Hence, this approach proves valuable in identifying cat exposure to different SARS-CoV-2 variants. Our results highlight the continued exposure of cats to SARS-CoV-2 and warrant coordinated surveillance efforts. Full article

The rapid emergence of evasive SARS-CoV-2 variants is an ongoing challenge for COVID-19 vaccinology. Traditional virus neutralization tests provide detailed datasets of neutralization titers against the viral variants. Such datasets are difficult to interpret and do not immediately inform of the sufficiency of the breadth of the antibody response. Some of these issues could be tackled using the antigenic cartography approach. In this study, we created antigenic maps using neutralization titers of sera from donors who received the Sputnik V booster vaccine after primary Sputnik V vaccination and compared them with the antigenic maps based on serum neutralization titers of Comirnaty-boosted donors. A traditional analysis of neutralization titers against the WT (wild-type), Alpha, Beta, Delta, Omicron BA.1, and BA.4/BA.5 variants showed a significant booster humoral response after both homologous (Sputnik V) and heterologous (Comirnaty) revaccinations against all of the studied viral variants. However, despite this, a more in-depth analysis using antigenic cartography revealed that Omicron variants remain antigenically distant from the WT, which is indicative of the formation of insufficient levels of cross-neutralizing antibodies. The implications of these findings may be significant when developing a new vaccine regimen. Full article

Bluetongue (BT) is a severe and economically important disease of ruminants that is widely distributed around the world, caused by the bluetongue virus (BTV). More than 28 different BTV serotypes have been identified in serum neutralisation tests (SNT), which, along with geographic variants (topotypes) within each serotype, reflect differences in BTV outer-capsid protein VP2. VP2 is the primary target for neutralising antibodies, although the basis for cross-reactions and serological variations between and within BTV serotypes is poorly understood. Recombinant BTV VP2 proteins (rVP2) were expressed in Nicotiana benthamiana, based on sequence data for isolates of thirteen BTV serotypes (primarily from Europe), including three ‘novel’ serotypes (BTV-25, -26 and -27) and alternative topotypes of four serotypes. Cross-reactions within and between these viruses were explored using rabbit anti-rVP2 sera and post BTV-infection sheep reference-antisera, in I-ELISA (with rVP2 target antigens) and SNT (with reference strains of BTV-1 to -24, -26 and -27). Strong reactions were generally detected with homologous rVP2 proteins or virus strains/serotypes. The sheep antisera were largely serotype-specific in SNT, but more cross-reactive by ELISA. Rabbit antisera were more cross-reactive in SNT, and showed widespread, high titre cross-reactions against homologous and heterologous rVP2 proteins in ELISA. Results were analysed and visualised by antigenic cartography, showing closer relationships in some, but not all cases, between VP2 topotypes within the same serotype, and between serotypes belonging to the same ‘VP2 nucleotype’. Full article

Global dispersion of high pathogenicity avian influenza (HPAI), especially that caused by H5 clade 2.3.4.4, has threatened poultry industries and, potentially, human health. An HPAI virus, A/northern pintail/Hokkaido/M13/2020 (H5N8) (NP/Hok/20) belonging to clade 2.3.4.4b, was isolated from a fecal sample collected at a lake in Hokkaido, Japan where migratory birds rested, October 2020. In the phylogenetic trees of all eight gene segments, NP/Hok/20 fell into in the cluster of European isolates in 2020, but was distinct from the isolates in eastern Asia and Europe during the winter season of 2017–2018. The antigenic cartography indicates that the antigenicity of NP/Hok/20 was almost the same as that of previous isolates of H5 clade 2.3.4.4b, whereas the antigenic distances from NP/Hok/20 to the representative strains in clade 2.3.4.4e and to a strain in 2.3.4 were apparently distant. These data imply that HPAI virus clade 2.3.4.4b should have been delivered by bird migration despite the intercontinental distance, although it was not defined whether NP/Hok/20 was transported from Europe via Siberia where migratory birds nest in the summer season. Given the probability of perpetuation of transmission in the northern territory, periodic updates of intensive surveys on avian influenza at the global level are essential to prepare for future outbreaks of the HPAI virus. Full article

Evaluation of the antigenic similarity degree between the strains of the influenza virus is highly important for vaccine production. The conventional method used to measure such a degree is related to performing the immunological assays of hemagglutinin inhibition. Namely, the antigenic distance between two strains is calculated on the basis of HI assays. Usually, such distances are visualized by using some kind of antigenic cartography method. The known drawback of the HI assay is that it is rather time-consuming and expensive. In this paper, we propose a novel approach for antigenic distance approximation based on deep learning in the feature spaces induced by hemagglutinin protein sequences and Convolutional Neural Networks (CNNs). To apply a CNN to compare the protein sequences, we utilize the encoding based on the physical and chemical characteristics of amino acids. By varying (hyper)parameters of the CNN architecture design, we find the most robust network. Further, we provide insight into the relationship between approximated antigenic distance and antigenicity by evaluating the network on the HI assay database for the H1N1 subtype. The results indicate that the best-trained network gives a high-precision approximation for the ground-truth antigenic distances, and can be used as a good exploratory tool in practical tasks. Full article

Human influenza A(H2N2) viruses emerged in 1957 and were replaced by A(H3N2) viruses in 1968. The antigenicity of human H2N2 viruses has been tested by using ferret antisera or mouse and human monoclonal antibodies. Here, we examined the antigenicity of human H2N2 viruses by using human plasma samples obtained from 50 aged individuals who were born between 1928 and 1933 and from 33 younger adult individuals who were born after 1962. The aged individuals possessed higher neutralization titers against H2N2 viruses isolated in 1957 and 1963 than those against H2N2 viruses isolated in 1968, whereas the younger adults who were born between 1962 and 1968 possessed higher neutralization titers against H2N2 viruses isolated in 1963 than those against other H2N2 viruses. Antigenic cartography revealed the antigenic changes that occurred in human H2N2 viruses during circulation in humans for 11 years, as detected by ferret antisera. These results show that even though aged individuals were likely exposed to more recent H2N2 viruses that are antigenically distinct from the earlier H2N2 viruses, they did not possess high neutralizing antibody titers to the more recent viruses, suggesting immunological imprinting of these individuals with the first H2N2 viruses they encountered and that this immunological imprinting lasts for over 50 years. Full article