Virus Strains Research Articles

Genomic characteristics, disease outcome and heterologous vaccine effectiveness among cases with SARS CoV-2 infection

BackgroundIn the pursuit of global health security, continuous monitoring of vaccine effectiveness across various viral strains emerges as a crucial imperative. The emergence of SARS-CoV-2 major variants of concern (VOCs), including Alpha, Beta, Delta, and Omicron, has added complexity to the COVID-19 vaccination landscape.ObjectivesTo assess illness severity, evaluate vaccine efficacy across varying doses and types, and determine effectiveness against major VOCs within the population.MethodsThis retrospective cohort study, conducted in Abu Dhabi, United Arab Emirates, focuses on a cohort of 44,073 SARS-CoV-2 positive cases from February 2021 to May 2022, dominated by the Delta and Omicron variants. The study employed a nested case-control design, analyzing hospital admissions for confirmed SARS-CoV-2 infection.ResultsVaccine effectiveness was higher among heterologus-boosted individuals at 87% (95% CI:79%-93%) compared to homologus-boosted individuals at 59% (95% CI: 48%-68%) and fully vaccinated, non-boosted adults at 53% (95% CI: 46%-59%). These findings highlight the importance of heterologous boosting, particularly against rapidly evolving viral variants, offering valuable insights for refining pandemic response strategies.ConclusionThe study underscores the critical need for ongoing assessment and adaptation of vaccination strategies to the evolving viral landscape.

Both chebulagic acid and punicalagin inhibit respiratory syncytial virus entry via multi-targeting glycoprotein and fusion protein.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, with no currently available small-molecule drugs that are both safe and effective. A major obstacle in antiviral drug development is the rapid emergence of drug-resistant viral strains. Targeting multiple viral compounds may help mitigate the development of resistance. Herein, we conducted a drug screening using the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to identify compounds that simultaneously target the RSV fusion (F) protein, glycoprotein (G), and the host heparan sulfate proteoglycans (HSPGs). From this screening, 10 candidate compounds were identified for their ability to interact with all three targets. Among these 10 candidates, chebulagic acid (CHLA) and punicalagin (PUG) demonstrated the most potent inhibition of RSV replication. In vitro dose-response assays confirmed the antiviral efficacy of CHLA (IC50: 0.07864 µM) and PUG (IC50: 0.08065 µM). Further experiments revealed both CHLA and PUG disrupt RSV attachment and membrane fusion by targeting the RSV-F and G proteins, rather than HSPG. Notably, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with docking assays predicting their binding sites at cysteines 176 and 182. Additionally, CHLA enhanced the conformational stability of the RSV-F protein before fusion. In an in vivo study, both CHLA and PUG were shown to alleviate RSV-induced pulmonary pathology by reducing viral titers, mitigating lung injury, and suppressing the inflammatory responses in the lungs. Our findings suggest that CHLA and PUG hold potential as therapeutic agents for RSV infection.IMPORTANCEA significant challenge in developing anti-respiratory syncytial virus (RSV) agents is the rapid emergence of resistant viral strains. Designing drugs that target multiple viral components can effectively reduce the likelihood of developing resistant strains. In this study, we screened compounds from the Antiviral Traditional Chinese Medicine Active Compound Library, aiming to simultaneously targe the RSV fusion (F) protein, glycoprotein (G), and host heparan sulfate proteoglycans (HSPGs). Our findings revealed that chebulagic acid (CHLA) and punicalagin (PUG) significantly inhibited RSV replication both in vitro and in vivo and interacted with all three targets. Both CHLA and PUG were able to disrupt RSV attachment and membrane fusion. Mechanistically, CHLA and PUG were found to bind to the CX3C motif of the RSV-G protein, with CHLA also enhancing the conformational stability of the RSV-F protein before fusion. In conclusion, our study suggests that CHLA and PUG hold promise as therapeutic agents against RSV infection.

Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation.

During the process by which human immunodeficiency virus (HIV-1) enters cells, the envelope glycoprotein (Env) trimer on the virion surface engages host cell receptors. Binding to the receptor CD4 induces Env to undergo transitions from a pretriggered, "closed" (State-1) conformation to more "open" (State 2/3) conformations. Most broadly neutralizing antibodies (bNAbs), which are difficult to elicit, recognize the pretriggered (State-1) conformation. More open Env conformations are recognized by poorly neutralizing antibodies (pNAbs), which are readily elicited during natural infection and vaccination with current Env immunogens. Env heterogeneity likely contributes to HIV-1 persistence by skewing antibody responses away from the pretriggered conformation. The conformationally flexible gp160 Env precursor on the infected cell or virion surface potentially presents multiple pNAb epitopes to the host immune system. Although proteolytic cleavage to produce the functional, mature Env trimer [(gp120/gp41)3] stabilizes State-1, many primary HIV-1 Envs spontaneously sample more open conformations. Here, we establish inducible cell lines that produce replication-defective HIV-1 particles with Env trimers stabilized in a pretriggered conformation. The mature Env is enriched on virus-like particles (VLPs). Using complementary approaches, we estimate an average of 25-50 Env trimers on each VLP. The stabilizing changes in Env limit the natural conformational heterogeneity of the VLP Env trimers, allowing recognition by bNAbs but not pNAbs. These defective VLPs provide a more homogeneous source of pretriggered Env trimers in a native membrane environment. Thus, these VLPs may facilitate the characterization of this functionally important Env conformation and its interaction with the immune system.IMPORTANCEA major impediment to the development of an effective HIV/AIDS vaccine is the inefficiency with which human immunodeficiency virus (HIV-1) envelope glycoproteins elicit antibodies that neutralize multiple virus strains. Neutralizing antibodies recognize a particular shape of the envelope glycoproteins that resides on the viral membrane before the virus engages the host cell. Here, we report the creation of stable cell lines that inducibly produce non-infectious HIV-like particles. The normally flexible envelope glycoprotein spikes on these virus-like particles have been stabilized in a conformation that is recognized by broadly neutralizing antibodies. These virus-like particles allow the study of the envelope glycoprotein conformation, its modification by sugars, and its ability to elicit desired neutralizing antibodies.

Effects of immunoproteasome inhibition on acute respiratory infection with murine hepatitis virus strain 1.

Inflammatory responses triggered by acute infection by respiratory viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drive morbidity and mortality. Infection of mice with murine hepatitis virus strain 1 (MHV-1), a mouse coronavirus, is a useful model to study the pathogenesis of coronavirus respiratory infections. The immunoproteasome is an inducible component of the ubiquitin proteasome system that is poised to contribute to multiple aspects of immune function, inflammation, and protein homeostasis during an infection. We used the MHV-1 model to define the role of the immunoproteasome in coronavirus pathogenesis. We found that immunoproteasome subunit expression increases in the lungs and the liver during acute MHV-1 respiratory infection. Inhibition of immunoproteasome activity did not affect MHV-1 replication but increased MHV-1-induced weight loss, mortality, and inflammation in lungs and livers. Thus, our findings indicate that the immunoproteasome is a critical protective host factor during coronavirus respiratory infection.

Nanoparticle-Supported, Rapid, Digital Quantification of Neutralizing Antibodies Against SARS-CoV-2 Variants.

The measurement of neutralizing immune responses to viral infection is essential, given the heterogeneity of human immunity and the emergence of new virus strains. However, neutralizing antibody (nAb) assays often require high-level biosafety containment, sophisticated instrumentation, and long detection times. Here, as a proof-of-principle, we designed a nanoparticle-supported, rapid, electronic detection (NasRED) assay to assess the neutralizing potency of monoclonal antibodies (mAbs) against SARS-CoV-2. The gold nanoparticles (AuNPs) coated with human angiotensin-converting enzyme 2 (ACE2) protein as nAb potency reporters were mixed with the mAbs to be tested, as well as streptavidin-conjugated multivalent spike (S) protein or their receptor binding domains (RBD). High-affinity and ACE2-competitive nAbs alter the S (or RBD)-to-ACE2 binding level and modulate AuNP cluster formation and precipitation. The amount of free-floating AuNP reporters is quantified by a semiconductor-based readout system that measures the AuNPs' optical extinction, producing nAb signals that can differentiate SARS-CoV-2 variants (Wuhan-Hu-1, Gamma, and Omicron). The modular design nature, short assay time (less than 30 minutes), and portable and inexpensive readout system make this NasRED-nAb assay applicable to measuring vaccine potency, immune responses to infection, and the efficacy of antibody-based therapies.

Genetic diversity and spread of recombinant coxsackievirus A4 in hand, foot, and mouth disease cases in Bangkok, Thailand: 2017–2023

Coxsackievirus A4 (CVA4) has recently become one of the most common causative agents of hand, foot, and mouth disease. The current study investigated the genetic diversity and spread of recombinant CVA4 by analyzing circulating genotypes and recombinant strains in Bangkok, Thailand, from 2017 to 2023. Partial VP1, 3Dpol, and whole genome sequencing of CVA4 samples collected from collaborating hospitals were conducted. Phylogenetic analysis of CVA4 VP1 and 3Dpol genome regions revealed discordance, indicating recombination. The predominant CVA4 genotype was C3, primarily observed in 2019. The predominant genotype in 2017 was C1. D2, commonly found in China, was occasionally observed. In nucleotide similarity analysis, intertypic recombination between CVA4 and EV-A during the evolutionary history of the virus was evident, particularly in the nonstructural region. The estimated emergence of genotypes C1 and C3 in Thailand occurred around 2014, with an evolutionary rate of 5.8 × 10− 3 nucleotide substitutions per site per year. Genotype D2 exhibited notable variability across both the entire genome and the structural protein region compared to genotype C. Monitoring the genetic diversity and circulation of recombinant CVA4 is crucial for identifying newly emerging virus strains, enabling prompt public health responses and containment efforts, and enhancing surveillance in Thailand.

Effect of wild-type vaccine doses on BA.5 hybrid immunity, disease severity, and XBB reinfection risk.

Vaccination against the wild-type (WT) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus did not produce detectable levels of neutralizing antibodies (NAbs) against the BA.5 strain before it emerged. However, coronavirus disease-2019 (COVID-19) severity varied highly between unvaccinated, partially vaccinated, and fully vaccinated individuals, for unknown reasons. We assessed the severity of BA.5 infection and the risk of XBB strain reinfection and measured serum levels of NAbs against WT, BA.5, and XBB.1.9.1 SARS-CoV-2 strains at varying time points in 1,373 individuals who received zero, one, two, or three WT vaccine doses. We found that two to three WT doses significantly increased WT and BA.5 NAb levels and reduced the incidence of COVID-19-associated pneumonia upon BA.5 strain infection compared to zero to one dose. Regarding XBB reinfection, those who received two to three doses and were infected with the BA.5 variant exhibited a significantly lower reinfection risk compared to those who received zero to one dose. RNA analysis revealed that the differentially expressed genes between the two to three dose and unvaccinated groups were enriched in B cell activation, cytokine-cytokine receptor interaction, complement, and monocyte activation functions-indicating that vaccination increased the antibody response and reduced inflammation. Our results suggest that multiple antigen exposures to either matched or unmatched SARS-COV-2 variants, through vaccination or infection, may be necessary to achieve significant immune imprinting.IMPORTANCEThe administration of coronavirus disease-2019 (COVID-19) vaccines that do not perfectly match the viral strains that individuals become infected with has been found to impact the resultant illness severity-although the precise mechanism underlying this phenomenon remains unclear. We assessed viral clearance, as well as serum levels of inflammatory cytokines and neutralizing antibodies (NAbs) against wild-type, BA.5, and XBB.1.9.1 variants of the severe acute respiratory syndrome coronavirus 2 among individuals who received varying doses of such strain-mismatched vaccines. Notably, vaccination with ≥2 doses of strain-mismatched COVID-19 vaccines appeared to stimulate the production of specific NAbs during infection with new variants, as well as attenuate the inflammatory response and enhance viral clearance. Such vaccination regimens can also reduce the risk of reinfection. These findings may be important for guiding the development of future COVID-19 vaccination strategies that target both matched and mismatched viral variants.

IFN-γ derived from activated human CD4+ T cells inhibits the replication of SARS-CoV-2 depending on cell-type and viral strain

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination elicit both T cell and B cell immune responses in immunocompetent individuals. However, the mechanisms underlying the antiviral effects mediated by CD4+ T cells are not fully understood. In this study, we analyzed the culture supernatant (SN) from polyclonally stimulated human CD4+ T cells as a model for soluble mediators derived from SARS-CoV-2-stimulated CD4+ T cells. Interestingly, this SN inhibited SARS-CoV-2 propagation in a viral strain- and host cell type-dependent manner. The original wild-type showed the highest susceptibility, whereas the Delta variant exhibited resistance in the human monocyte cell line. In addition, antibody-dependent enhancement (ADE) of infection with the original strain was also abolished in the presence of the SN. The findings showed that the inhibitory effect on viral propagation by the SN was mostly attributed to interferon-γ (IFN-γ) that was present in the SN. These results highlight the potential role of IFN-γ as an anti-SARS-CoV-2 mediator derived from CD4+ T cells, and suggest that we need to understand the SARS-CoV-2 strain-dependent sensitivity to IFN-γ in controlling clinical outcomes. In addition, characterization of new SARS-CoV-2 variants in terms of IFN-γ-sensitivity will have important implications for selecting therapeutic strategies.

A survey on the occurrence of papaya ringspot virus-P (PRSV-P) in Malaysia and genetic diversity assessment of the coat protein region.

Papaya ringspot virus (PRSV) is a plant virus transmitted by aphids that has spread throughout many countries, including Malaysia, causing yield losses and economic impacts to the papaya industry worldwide. PRSV infection in papaya-distinctive ring-shaped patterns on papaya leaves resulted in stunted growth and reduced fruit quality. Management strategies such as the use of resistant varieties, cultural practices, and vector control are employed to mitigate the spread of PRSV. However, the evolution of new virus strains and the uncertainties posed by climate change pose ongoing challenges for the management of PRSV worldwide. Therefore, in this present study, we aim to confirm the presence of PRSV in symptomatic papaya leaves, to depict the current status of PRSV in Malaysia. Using reverse-transcription PCR (RT-PCR) targeting PRSV partial nuclear inclusion b protein (NIb) and coat protein (CP), 13 out of 40 papaya leaves collected were found positive for the PRSV strain-P (PRSV-P). Nucleotide analysis revealed a high similarity with strains from Taiwan and India, showing 96.83%, 97.03%, and 97.03% identity with the Taiwan strains (DQ340771, AY027810) and the India strain (KJ755852), respectively. Compared to the CP gene of Malaysian isolates reported in 2016 (EU082207), several nonsynonymous mutations have been discovered suggesting genetic diversity within the PRSV population in Malaysia. Overall, this study confirms the current circulation of PRSV infection in Malaysia since it was first identified in Johore in 1991. The re-occurrence of PRSV-P in this study highlights the need for continuous monitoring and targeted management strategies to prevent the further spread of PRSV-P in Malaysia.

Phytochemical composition and therapeutic potential of Caralluma edulis a cholistani plant

This study explores C. edulis, a plant indigenous to the Cholistan desert, locally known as Pimpa or Seetu, traditionally consumed as a vegetable. Our research aimed to comprehensively analyze its phytochemical constituents, and evaluate its antibacterial, antioxidant, antiviral, anti-inflammatory, antidiabetic, and antipyretic potentials. Utilizing a range of extracts including methanol (MtOH), ethanol (EtOH), ethyl acetate (EA), n-hexane (n-hex), dichloromethane (DCM), and aqueous (Aq), for effective extraction of phytochemicals from C. edulis. Standard biochemical assays and High-Performance Liquid Chromatography-Photodiode Array (HPLC-PDA) were used for analysis of phenolic compounds. Antibacterial effect(s) were confirmed through disc diffusion method and min inhibitory concentrations (MICs). The antioxidant activity was assessed through the Ferric Reducing Antioxidant Power (FRAP) assay and the DPPH radical scavenging method. In vivo antiviral potential was assessed through Hemagglutination (HA) test. Anti-inflammatory, antidiabetic, and antipyretic activities were performed on female albino rats using carrageenan, alloxan monohydrate and yeast-induced methods, respectively. Statistical analysis was done using standard one way ANOVA.Our findings revealed a rich diversity of phenolic compounds and the presence of proteins, alkaloids, and carbohydrates in C. edulis. MtOH and n-hex extracts demonstrated deep antiviral activity against various viral strains. In vivo toxicology studies indicated no significant toxicity at doses up to 5 g/kg. The DCM extract has shown notable anti-inflammatory effects, and EA extract was leading in antipyretic activity. All extracts, except MtOH, exhibited antidiabetic properties.In conclusion, C. edulis emerges not only as a valuable nutritional source but also as a potent alternative medicinal resource, offering wide range of therapeutic benefits.

Three positively charged binding sites on the eastern equine encephalitis virus E2 glycoprotein coordinate heparan sulfate- and protein receptor-dependent infection.

Naturally circulating strains of eastern equine encephalitis virus (EEEV) bind heparan sulfate (HS) receptors and this interaction has been linked to its neurovirulence. Previous studies associated EEEV-HS interactions with three positively charged amino acid clusters on the E2 glycoprotein. One of these sites has recently been reported to be critical for binding EEEV to very-low-density lipoprotein receptor (VLDLR), an EEEV receptor protein. The proteins apolipoprotein E receptor 2 (ApoER2) isoforms 1 and 2, and LDLR have also been shown to function as EEEV receptors. Herein, we investigate the individual contribution of each HS interaction site to EEEV HS- and protein receptor-dependent infection in vitro and EEEV replication in animals. We show that each site contributes to both EEEV-HS and EEEV-protein receptor interactions, providing evidence that altering these interactions can affect disease in mice and eliminate mosquito infectivity. Thus, multiple HS-binding sites exist in EEEV E2, and these sites overlap functionally with protein receptor interaction sites, with each type of interaction contributing to tissue infectivity and disease phenotypes.

Comparative profile of the human coronaviruses

The coronavirus disease (COVID-19), a respiratory illness is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is a strain of human corona virus (HCoV) and is infectious in humans. Seven types of human coronaviruses, namely, human coronavirus 229E (HCoV-229E), human coronavirus OC43 (HCoV-OC43), severe acute respiratory syndrome coronavirus SARS-CoV-1, human coronavirus NL63 (HCoV-NL63), human coronavirus HKU1 (HCoV-HKU1), middle east respiratory syndrome-related coronavirus (MERS-CoV) and SARS-CoV-2 have been identified so far. Almost all these viruses spread between people through respiratory droplets produced from coughs or sneezes; the target cells being the epithelial cells of the respiratory tract. In this review, a brief comparative study of these pathogenic CoVs in humans is done which enables an understanding of the evolution in these diseases over a span of almost a century. This review will provide an insight into all HCoVs identified till date.

Impact of Different Foot and Mouth Disease Vaccine Schemes in Cross-Neutralization Against Heterologous Serotype O Strains in Cattle.

The high antigenic variability of the foot-and-mouth disease virus (FMDV) represents a challenge for developing prophylactic strategies, stressing the need for research into vaccines offering broad protection against a range of virus strains. Here, the heterotypic cross-reaction using different vaccine schemes against serotype O strains was studied, evaluating the impact of revaccination, antigen dose, and incorporation of additional FMDV serotypes. Naïve cattle were immunized with seven distinct FMDV vaccines, receiving three doses of the same formulation at 0, 28, and 56 days post-primary vaccination (dpv). Serum samples were collected up to 70 dpv and tested by a virus-neutralizing test against serotype O strains from a South American lineage and two strains representative of two Asian lineages. Our results showed that vaccines containing the ME-SA topotype O1/Campos strain developed cross-neutralizing responses against the two Asian viruses after the first vaccination. In contrast, significant heterotypic neutralizing antibody titers against the homologous topotype strain were only found after the second vaccination, indicating that the phylogenic relationship may differ from the antigenic profiles for these two viruses. The amount of the O1/Campos strain and the revaccination were essential factors for neutralization against the homologous- and heterologous-type O FMDV viruses. The strain composition of the vaccine was only relevant for cross-neutralization against one of the Asian strains, suggesting potential intra-serotypic divergences for this pattern.

Rapid production of recombinant rotaviruses by overexpression of NSP2 and NSP5 genes with modified nucleotide sequences.

Reverse genetics systems for rotaviruses (RV) facilitate the generation of genetically engineered RVs by transfection of 11 plasmids encoding 11 genomic viral RNA segments. In addition to viral genome expression, overexpression of NSP2 and NSP5 has been used to increase the rescue efficiency of recombinant RVs. Here, we showed that the overexpression of nucleotide sequence-modified NSP2 and NSP5 enabled the rapid and efficient production of recombinant RVs. Using improved reverse genetics, we established a reverse genetics system for human and bovine RV clinical isolates, as well as laboratory strains of bovine RV (NCDV and UK) and porcine RV (Gottfried). In addition, we rescued low-replicating recombinant RVs carrying a mutant NSP4 lacking the double-layered particle-binding domain, which was deficient in the efficient production of mature virions. These advancements in reverse genetics enabled the generation of molecular clones of RV clinical isolates and recombinant RVs harboring critical amino acid mutations, offering a versatile platform for investigating RV biology and pathogenesis.IMPORTANCERecombinant rotavirus (RV) synthesis via reverse genetics relies on both the viral propagation capacity and the efficiency of the experimental system. Since the establishment of our reverse genetics system, several enhancements have been implemented to augment the rescue efficiency. Nevertheless, challenges persist in generating RV clinical strains and recombinant viruses with low replication capacities. Notably, this improved reverse genetics system successfully facilitated the establishment of molecular clones of human and bovine RV clinical isolates. Fecal samples from patients with RV typically harbor quasi-species or, occasionally, multiple genotypes of RV. In the present study, we performed the genetic sequencing of clinical viral strains during the early propagation stages in cultured cells. Subsequently, infectious viruses were synthesized, allowing the characterization of circulating viruses in nature. This approach provides valuable insights into the genetic diversity and dynamics of RV populations and contributes to a more comprehensive understanding of viral pathogenesis and evolution.

Review of domestic test systems for detecting current or past SARS‑CoV‑2 infection using enzyme‑linked immunosorbent assay

Introduction. Rapid and reliable assessment of circulating antibody levels to SARS-CoV-2 remains the current challenge for monitoring and preventing the spread of COVID-19. As the risk of emergence and dissemination of new viral strains continues to grow, epidemiologic research is also becomes increasingly important. The enzyme-linked immunosorbent assay (ELISA) is useful to assess the vaccination effectiveness and the need for revaccination, the proportion of post-disease and vaccinated individuals, and to monitor population immunity. This article provides an overview of the local ELISA kits currently available for the detection of antibodies against SARS-CoV-2 viral proteins, with a comparison to the certified kit by Mediagnost Ltd. (Germany).The aim. Laboratory testing of seven domestic reagent kits for the determination of antibodies to SARS-CoV-2 viral proteins by ELISA in comparison with the certified test system “Anti-SARS-CoV-2 ELISA E 111-IVD” (Mediagnost Ltd., Reutlingen, Germany).Materials and methods. The study included 80 serum samples from conditionally healthy donors: experimental group (n=70, serum samples collected after 2019) and control group (n=10, serum samples collected before 2018). The experimental group is comprised of non-infected and post-disease individuals; a proportion of those were vaccinated against COVID-19.Results and conclusions. The data obtained indicate high reproducibility, sensitivity (100 %), and specificity for all domestic ELISA kits in detecting both post-disease (90–95 %) and vaccinated volunteers (100 %). The main quality criteria of the obtained results were comparable to those for the certified test system, “Anti-SARS-CoV-2 ELISA E 111-IVD” (Mediagnost Ltd., Germany). All kits detecting IgG to the receptor-binding domain (RBD) and to the S-glycoprotein were effective for the reliable assessment of antibody production after the vaccination. Kits for the detection of antibodies to the RBD and/or viral nucleocapsid are useful for identifying unvaccinated post-disease individuals.

Genomics-based timely detection of dengue virus type I genotypes I and V in Uruguay

This study details a genomics-based approach for the early detection of mosquito-borne pathogens, marked by Uruguay's first ever complete genomic sequencing of Dengue Virus type I genotypes I and V. This pioneering effort has facilitated the prompt identification of these genotypes within the country, enabling Uruguayan public health authorities to develop timely and effective response strategies. Further integrated into this approach is a climate-driven suitability measure, closely associated with Dengue case reports and indicative of the local climate's role in the virus's transmission in the country within the changing climate context. The detection of multiple DENV-1 genotypes co-circulating in Uruguay underscores the necessity for proactive surveillance, particularly at borders, to prevent the introduction and dissemination of novel viral strains within the country and the region. This approach aids in facilitating prompt public health responses and intervention strategies, which are crucial in mitigating the impact of dengue outbreaks.

Inno4Vac Workshop Report Part 1: Controlled Human Influenza Virus Infection Model (CHIVIM) Strain Selection and Immune Assays for CHIVIM Studies, November 2021, MHRA, UK.

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including the development of CHIMs for influenza, respiratory syncytial virus and Clostridioides difficile. This report (in two parts) summarises a workshop held at the MHRA in 2021, focused on how to select CHIM candidate strains of influenza and respiratory syncytial virus (RSV) based on desirable virus characteristics and which immune assays would provide relevant information for assessing pre-existing and post-infection immune responses and defining correlates of protection. This manuscript (Part 1) summarises presentations and discussions centred around influenza CHIMs and immune assays (a second manuscript summarises RSV CHIM and immune assays: Inno4Vac workshop report Part 2: RSV CHIM strain selection and immune assays for RSV CHIM studies, November 2021, MHRA, UK).

Measures of Population Immunity Can Predict the Dominant Clade of Influenza A (H3N2) in the 2017-2018 Season and Reveal Age-Associated Differences in Susceptibility and Antibody-Binding Specificity.

For antigenically variable pathogens such as influenza, strain fitness is partly determined by the relative availability of hosts susceptible to infection with that strain compared with others. Antibodies to the hemagglutinin (HA) and neuraminidase (NA) confer substantial protection against influenza infection. We asked if a cross-sectional antibody-derived estimate of population susceptibility to different clades of influenza A (H3N2) could predict the success of clades in the following season. We collected sera from 483 healthy individuals aged 1 to 90 years in the summer of 2017 and analyzed neutralizing responses to the HA and NA of representative strains using focus reduction neutralization tests (FNRT) and enzyme-linked lectin assays (ELLA). We estimated relative population-average and age-specific susceptibilities to circulating viral clades and compared those estimates to changes in clade frequencies in the following 2017-2018 season. The clade to which neutralizing antibody titers were lowest, indicating greater population susceptibility, dominated the next season. Titer correlations between viral strains varied by age, suggesting age-associated differences in epitope targeting driven by shared past exposures. Yet substantial unexplained variation remains within age groups. This study indicates how representative measures of population immunity might improve evolutionary forecasts and inform selective pressures on influenza.

Bio Nanoparticles as Antimicrobial Agents

One such novel technology is nanotechnology, which has been revolutionized in health care, textile, materials, information and communication technology, and energy sectors too. There are many ways depicted in various literatures to synthesize silver nanoparticles. These include physical, chemical, and biological methods. The physical and chemical methods are numerous in number, and many of these methods are expensive or use toxic substances which are major factors that make them “not so favored” methods of synthesis. An alternate, feasible method to synthesize silver nanoparticles is to employ biological methods of using microbes and plants. Biotechnology has considered a safe agricultural tool to enhance crop protection, subsequently to produce more agricultural products, improve food process, nutritional value, and better flavor. Side by side it has detrimental ecological consequences such as spreading genetically engineered genes to indigenous plants, elevated toxicity, which may transmit through food chain, disrupting nature’s system of pest control, developing new weeds or virus strains, biodiversity loss, and insecticidal resistance (Goswami et al., 2010). Hence, it is necessary to bring forth new innovative technology/methods to overcome the above mentioned problems. The potential application of biogenic nanoparticles as antimicrobial agents will be also reviewed. The mechanism of action of nanoparticles as bactericidal and antifungal agents will be highlighted in this chapter.

Post-vaccination immunity and pneumonia incidence in medical workers in response to various flu vaccination regimens between the 1st and 2nd peaks of COVID-19 morbidity

Background.In the absence of a vaccine against SARS-CoV-2, seasonal influenza vaccination during the pandemic contributed to lowered COVID-19 susceptibility and severity. The study was aimed to assess the state of post-influenza vaccination immunity, pneumonia frequency and severity in medical workers after using various flu vaccination regimens, between the 1st and 2nd peaks of COVID-19 epidemic rise.Materials and methods.Comparatively analyzed data on the levels of antibodies against influenza virus strains and pneumonia incidence in 487 medical workers was carried out: 1st group — unvaccinated in 2020–2021 (n = 281), 2nd group — vaccinated against influenza (Sovigripp), (n = 98), 3rd group — received combined vaccination against influenza and pneumococcus (Prevenar 13), (n = 108).Results.6 months after vaccination, the highest rates of influenza virus were detected in the A(H3N2), the level of seroprotection (≥ 1:40) ranged from 49.0% in unvaccinated (1st group) to 53.4–53.2% in those who received combined vaccination (group III), as well as influenza alone (2nd group), p 0.05; for strain A(H1N1) the level of seroprotection in 1st group is 24.5%, lower (p 0.04) than in 2nd group — 32.7%, but does not differ from the levels of 40.4% in group III; for strain B the level of seroprotection is the lowest ranging from 19.4% in the group of unvaccinated subjects up to 22.4% in 2nd group and 23.4% in 3rd group. The pneumonia incidence in 1st group (3.9%), 2nd group (3.1%), 3rd group (4.6%) did not differ, however, among all vaccinated subjects severity of pneumonia clinical course was mild, whereas in unvaccinated employees, except for mild course (45.4%, 5 out of 11 people) pneumonia in 36.4% (4 out of 11 people) cases was assessed as moderate and in 18.2% (2 out of 11 people) cases — severe with fatal outcomes.Conclusion.The study showed that 6 months after seasonal influenza immunization between the 1st and 2nd peaks of COVID-19 epidemic rise, the immunogenicity of the vaccine meets the CPMP criterion for the A(H3N2) strain. In vaccinated patients, the proportion of pneumonia with COVID-19 clinical picture was mild in 100% of cases, and in unvaccinated patients in 36.4% of cases — of moderate severity and in 18.2% — severe with fatal outcome.