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© 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) ; An intriguing and remarkable feature of African trypanosomes is their antigenic variation system, mediated by the variant surface glycoprotein (VSG) family and fundamental to both immune evasion and disease epidemiology within host populations. Recent studies have revealed that the VSG repertoire has a complex evolutionary history. Sequence diversity, genomic organization, and expression patterns are species-specific, which may explain other variations in parasite virulence and disease pathology. Evidence also shows that we may be underestimating the extent to what VSGs are repurposed beyond their roles as variant antigens, establishing a need to examine VSG functionality more deeply. Here, we review sequence variation within the VSG gene family, and highlight the many opportunities to explore their likely diverse contributions to parasite survival. ; S.S.P. is funded by the European Union's Horizon 2020 research and innovation program through a Marie Skłodowska-Curie Individual Standard European Fellowship , under grant agreement no. 839960 . A.P.J. is funded by a Leverhulme Trust Research Fellowship ( RF-2020-413 ). L.M.F. is an Investigator CEEC of the Fundação para a Ciência e a Tecnologia ( CEECIND/03322/2018 ) and the laboratory is funded by the ERC (FatTryp, ref. 771714 ). ; info:eu-repo/semantics/publishedVersion

BACKGROUND: In the absence of microscopy, Plasmodium falciparum histidine-rich proteins 2 (PfHRP2)-based rapid diagnostic tests (RDTs) are recommended for the diagnosis of falciparum malaria, particularly in endemic regions. However, genetic variability of the pfhrp2 gene threatens the usefulness of the test due to its impact on RDT sensitivity. This study aimed to investigate the diversity of pfhrp2 in malaria cases among children in Ghana. METHODS: A cross-sectional study was conducted at the Adidome Government Hospital in the Volta Region of Ghana. A total of 50 children with mean age of 6.6 ± 3.5 years and diagnosed falciparum malaria were included. Blood samples were collected for complete blood count, malaria parasite identification and counting using auto analyzer and microscopy, respectively. DNA was isolated from blood-spotted Whatman filters, amplified and sequenced. Nucleotide sequences were translated in silico to corresponding amino acids and the deduced amino acids sequences were analyzed for diversity using Mega X. RESULTS: The number of repeats and number of each repeat within PfHRP2 varied between isolates. Twelve rare PfHRP2 repeat types, two of which are previously unreported, were identified in this study. The HRP2 sequence obtained in this study shared high similarities with isolates from Kenya. Using Baker's regression model, Group B was the highest occurring type (58.0%). Screening of all sequences for epitopes recognized by PfHRP2-specific monoclonal antibodies (mAbs), the predominant motif was AHHAADAHH, which is recognized by the C1-13 mAbs. CONCLUSION: This study reports diversity of P. falciparum HRP2 in samples from Ghanaian children with symptomatic malaria. The findings of this study highlight the existence of extra amino acid repeat types which adds to the PfHRP2 antigenic variability.

From a regulatory perspective foot-and-mouth disease (FMD) vaccines represent a special case due to the number and antigenic diversity of strains that might be used alone or in combination within the context of an authorisation. New guidelines have been developed proposing that an FMD vaccine should be defined as a formulation of ingredients including defined amounts of one or more antigens that vary only in the number and types of antigen present. These new guidelines are in line with those previously proposed for equine influenza vaccines. Slaughter policies being less and less popular in the European Union, there is a tendency to use so-called marker vaccines associated with a companion diagnostic test. Such methodology has already been used for vaccination against pseudo-rabies and infectious bovine rhinotracheitis. Sub-unit marker vaccines against classical swine fever have also been developed; such vaccines are also envisaged against foot-and-mouth disease; it would permit, if satisfying defined criteria, to distinguish vaccinated from infected animals. ; Peer reviewed

Foot-and-mouth disease (FMD) is a highly contagious disease of cloven-hoofed animals. The disease was initially described in the 16th century and was the first animal pathogen identified as a virus. Recent FMD outbreaks in developed countries and their significant economic impact have increased the concern of governments worldwide. This review describes the reemergence of FMD in developed countries that had been disease free for many years and the effect that this has had on disease control strategies. The etiologic agent, FMD virus (FMDV), a member of the Picornaviridae family, is examined in detail at the genetic, structural, and biochemical levels and in terms of its antigenic diversity. The virus replication cycle, including virus-receptor interactions as well as unique aspects of virus translation and shutoff of host macromolecular synthesis, is discussed. This information has been the basis for the development of improved protocols to rapidly identify disease outbreaks, to differentiate vaccinated from infected animals, and to begin to identify and test novel vaccine candidates. Furthermore, this knowledge, coupled with the ability to manipulate FMDV genomes at the molecular level, has provided the framework for examination of disease pathogenesis and the development of a more complete understanding of the virus and host factors involved.

Scrub typhus has struck back, albeit with renewed vigour, impacting areas with previously known endemicity as also impressing newer expanses. It is not surprising, therefore, that Scrub typhus has emerged as a leading cause of public health concern globally as well as in India, but are we ready to take on the challenge? Over the last decade, there has been a global increase in the number of outbreaks of Scrub typhus, be it the military occupied areas or the civil population at large. The innumerable outbreaks of Scrub typhus, although disconcerting, have nonetheless contributed phenomenally towards better understanding of the dynamics of scrub typhus. There have been significant contributions to awareness of the disease amongst medical professionals, scrub typhus as a cause of Acute Undifferentiated Febrile Illness (AUFI) and newer clinical manifestation – Acute Encephalitis Syndrome (AES), availability and advances in diagnostics and management, man-vector-pathogen interactions, new records of Leptotrombidium species, newer vectors and Orientia species. Antigenic diversity and the varied clinical presentation of scrub typhus, absence of scrub typhus surveillance system and a lack of political will to recognize the disease as one of the important reemerging public health problem are areas seeking concerted deliberations and actions so that the challenges posed by scrub typhus can be addressed.

The human respiratory tract contains a highly adapted microbiota including commensal and opportunistic pathogens. Noncapsulated or nontypable Haemophilus influenzae (NTHi) is a human-restricted member of the normal airway microbiota in healthy carriers and an opportunistic pathogen in immunocompromised individuals. The duality of NTHi as a colonizer and as a symptomatic infectious agent is closely related to its adaptation to the host, which in turn greatly relies on the genetic plasticity of the bacterium and is facilitated by its condition as a natural competent. The variable genotype of NTHi accounts for its heterogeneous gene expression and variable phenotype, leading to differential host-pathogen interplay among isolates. Here we review our current knowledge of NTHi diversity in terms of genotype, gene expression, antigenic variation, and the phenotypes associated with colonization and pathogenesis. The potential benefits of NTHi diversity studies discussed herein include the unraveling of pathogenicity clues, the generation of tools to predict virulence from genomic data, and the exploitation of a unique natural system for the continuous monitoring of long-term bacterial evolution in human airways exposed to noxious agents. Finally, we highlight the challenge of monitoring both the pathogen and the host in longitudinal studies, and of applying comparative genomics to clarify the meaning of the vast NTHi genetic diversity and its translation to virulence phenotypes. ; This work has been funded by grants from the Health Institute Carlos III (ISCIII), grant PI09/00130, and from the Health Department of the Government of Navarra, Spain (Call 2011) to J.G., and by grant PI09/01904 (ISCIII) to J. Liñares. CIBERES is an initiative from ISCIII, Spain. ; Peer Reviewed

The ongoing evolution of SARS-CoV-2 has resulted in the emergence of Omicron, which displays striking immune escape potential. Many of its mutations localize to the spike protein ACE2 receptor-binding domain, annulling the neutralizing activity of most therapeutic monoclonal antibodies. Here we describe a receptor-blocking human monoclonal antibody, 87G7, that retains ultrapotent neutralization against SARS-CoV-2 variants including the Alpha, Beta, Gamma, Delta and Omicron (BA.1/BA.2) Variants-of-Concern (VOCs). Structural analysis reveals that 87G7 targets a patch of hydrophobic residues in the ACE2-binding site that are highly conserved in SARS-CoV-2 variants, explaining its broad neutralization capacity. 87G7 protects mice and/or hamsters against challenge with all current SARS-CoV-2 VOCs. Our findings may aid the development of sustainable antibody-based strategies against COVID-19 that are more resilient to SARS-CoV-2 antigenic diversity. ; The MANCO project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 101003651). This work made use of the Dutch national e infrastructure with the support of the SURF Cooperative using grant no. EINF-2453. This research was funded by the Deutsche Forschungsgemeinschaft (DFG; German Research Foundation) - 398066876/GRK 2485/1; BMBF (Federal Ministry of Education and Research) project entitled RAPID (Risk assessment in re-pandemic respiratory infectious diseases), 01KI1723G, Ministry of Science and Culture of Lower Saxony in Germany (14 - 76103-184 CORONA-15/20) ; No

Several African swine fever (ASF) outbreaks in domestic pigs have been reported in Burundi and Malawi and whole-genome sequences of circulating outbreak viruses in these countries are limited. In the present study, complete genome sequences of ASF viruses (ASFV) that caused the 2018 outbreak in Burundi (BUR/18/Rutana) and the 2019 outbreak in Malawi (MAL/19/Karonga) were produced using Illumina next-generation sequencing (NGS) platform and compared with other previously described ASFV complete genomes. The complete nucleotide sequences of BUR/18/Rutana and MAL/19/Karonga were 176,564 and 183,325 base pairs long with GC content of 38.62 and 38.48%, respectively. The MAL/19/Karonga virus had a total of 186 open reading frames (ORFs) while the BUR/18/Rutana strain had 151 ORFs. After comparative genomic analysis, the MAL/19/Karonga virus showed greater than 99% nucleotide identity with other complete nucleotides sequences of p72 genotype II viruses previously described in Tanzania, Europe and Asia including the Georgia 2007/1 isolate. The Burundian ASFV BUR/18/Rutana exhibited 98.95 to 99.34% nucleotide identity with genotype X ASFV previously described in Kenya and in Democratic Republic of the Congo (DRC). The serotyping results classified the BUR/18/Rutana and MAL/19/Karonga ASFV strains in serogroups 7 and 8, respectively. The results of this study provide insight into the genetic structure and antigenic diversity of ASFV strains circulating in Burundi and Malawi. This is important in order to understand the transmission dynamics and genetic evolution of ASFV in eastern Africa, with an ultimate goal of designing an efficient risk management strategy against ASF transboundary spread.

Infections of adenovirus type 4 (Ad4) and Ad7 were discovered among previously vaccinated individuals through febrile respiratory illness surveillance at military recruit camps. Genetic analysis was performed on these isolates and a sample of adenovirus isolates from unvaccinated patients. Antigenic regions of the adenovirus hexon gene from 21 vaccinated and 31 unvaccinated patients were sequenced and compared to homologous regions of Ad4 and Ad7 vaccine strains and of other representative hexon sequences archived in GenBank. The phylogenetic distribution of sequences from vaccinated individuals closely resembled those from unvaccinated individuals. The most common Ad7 strain was the Ad7d2 hexon genotype, and the most common Ad4 strain was a genotype nearly identical to the recently discovered Z-G 95-873 Ad4 variant. Near exclusive isolation of Ad4 since 1999 indicates that the Ad4 variant is currently responsible for the vast majority of adenovirus morbidity in military recruit camps. Different ratios of nonsynonymous to synonymous nucleotide substitution rates in known antigenic regions compared to nonantigenic regions indicated positive selection for diversity in the antigenic regions and purifying selection in the nonantigenic regions.

The paper presents data on the level of serum immunoglobulins in residents of the North and Arctic of the European territory of the Russian Federation. In people living in the Arctic, the average concentration of IgM, IgA and IgE is 1.4–2.6 times higher, the frequency of elevated concentrations is 2.4–8.8 times higher. A high frequency of IgG deficiency of 72.3% was established, which indicates inhibition of switching of antibody synthesis with a predominant predominance of IgM and IgA. In an unfavorable climate, the spectrum of antigenic structures increases and expands significantly. Activation of antibody production is due to an increased level of antigenic effects on the body and an increase in the content, diversity in the intravascular environment of tissue metabolism products with the properties of autoantigens. It was revealed that the concentration of immunoglobulins is significant in the formation of circulating immune complexes (CIC). In residents of the Arctic of the European territory of the Russian Federation, increased concentrations of IgM and IgA are associated with an increase in the content of neutrophil granulocytes and interferon-gamma cytokine (IFN-γ), which in turn is aimed at ensuring the effectiveness of the clearance of waste products in hypoxia.

Licensed vaccines or therapeutics are rarely available for pathogens with epidemic or pandemic potential. Developing interventions for specific pathogens and defining generalizable approaches for related pathogens is a global priority and inherent to the UN Sustainable Development Goals. Nipah virus (NiV) poses a significant epidemic threat, and zoonotic transmission from bats-to-humans with high fatality rates occurs almost annually. Human-to-human transmission of NiV has been documented in recent outbreaks leading public health officials and government agencies to declare an urgent need for effective vaccines and therapeutics. Here, we evaluate NiV vaccine antigen design options including the fusion glycoprotein (F) and the major attachment glycoprotein (G). A stabilized prefusion F (pre-F), multimeric G constructs, and chimeric proteins containing both pre-F and G were developed as protein subunit candidate vaccines. The proteins were evaluated for antigenicity and structural integrity using kinetic binding assays, electron microscopy, and other biophysical properties. Immunogenicity of the vaccine antigens was evaluated in mice. The stabilized pre-F trimer and hexameric G immunogens both induced serum neutralizing activity in mice, while the post-F trimer immunogen did not elicit neutralizing activity. The pre-F trimer covalently linked to three G monomers (pre-F/G) induced potent neutralizing antibody activity, elicited responses to the greatest diversity of antigenic sites, and is the lead candidate for clinical development. The specific stabilizing mutations and immunogen designs utilized for NiV were successfully applied to other henipaviruses, supporting the concept of identifying generalizable solutions for prototype pathogens as an approach to pandemic preparedness.