Animal Models Utilized for the Development of Influenza Virus Vaccines.
TL;DR: In this article, the authors describe seasonal and novel influenza virus vaccines and highlight important animal models used to develop them, and highlight the importance of animal models in the development of influenza vaccines.
About: This article is published in Vaccine.The article was published on 2021-07-14 and is currently open access. It has received 9 citations till now. The article focuses on the topics: Antigenic drift.
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TL;DR: The C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus is developed and utilized and a series of robustly elicited individual CD4 T cell peptide specificities are identified, enabling more sophisticated analyses of influenza B virus infection.
Abstract: The adaptive T cell response to influenza B virus is understudied, relative to influenza A virus, for which there has been considerable attention and progress for many decades. Here, we have developed and utilized the C57BL/6 mouse model of intranasal infection with influenza B (B/Brisbane/60/2008) virus and, using an iterative peptide discovery strategy, have identified a series of robustly elicited individual CD4 T cell peptide specificities. The CD4 T cell repertoire encompassed at least eleven major epitopes distributed across hemagglutinin, nucleoprotein, neuraminidase, and non-structural protein 1 and are readily detected in the draining lymph node, spleen, and lung. Within the lung, the CD4 T cells are localized to both lung vasculature and tissue but are highly enriched in the lung tissue after infection. When studied by flow cytometry and MHC class II: peptide tetramers, CD4 T cells express prototypical markers of tissue residency including CD69, CD103, and high surface levels of CD11a. Collectively, our studies will enable more sophisticated analyses of influenza B virus infection, where the fate and function of the influenza B-specific CD4 T cells elicited by infection and vaccination can be studied as well as the impact of anti-viral reagents and candidate vaccines on the abundance, functionality, and localization of the elicited CD4 T cells.
3 citations
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TL;DR: In this article , the authors used the swine influenza challenge model to assess whether α-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine (TX98ΔNS1) encoding a truncated NS1 protein.
Abstract: Natural killer T (NKT) cells activated with the glycolipid ligand α-galactosylceramide (α-GalCer) stimulate a wide variety of immune cells that enhance vaccine-mediated immune responses. Several studies have used this approach to adjuvant inactivated and subunit influenza A virus (IAV) vaccines, including to enhance cross-protective influenza immunity. However, less is known about whether α-GalCer can enhance live attenuated influenza virus (LAIV) vaccines, which usually induce superior heterologous and heterosubtypic immunity compared to non-replicating influenza vaccines. The current study used the swine influenza challenge model to assess whether α-GalCer can enhance cross-protective immune responses elicited by a recombinant H3N2 LAIV vaccine (TX98ΔNS1) encoding a truncated NS1 protein. In one study, weaning pigs were administered the H3N2 TX98ΔNS1 LAIV vaccine with 0, 10, 50, and 100 μg/kg doses of α-GalCer, and subsequently challenged with a heterologous H3N2 virus. All treatment groups were protected from infection. However, the addition of α-GalCer appeared to suppress nasal shedding of the LAIV vaccine. In another experiment, pigs vaccinated with the H3N2 LAIV, with or without 50 μg/kg of α-GalCer, were challenged with the heterosubtypic pandemic H1N1 virus. Pigs vaccinated with the LAIV alone generated cross-reactive humoral and cellular responses which blocked virus replication in the airways, and significantly decreased virus shedding. On the other hand, combining the vaccine with α-GalCer reduced cross-protective cellular and antibody responses, and resulted in higher virus titers in respiratory tissues. These findings suggest that: (i) high doses of α-GalCer impair the replication and nasal shedding of the LAIV vaccine; and (ii) α-GalCer might interfere with heterosubtypic cross-protective immune responses. This research raise concerns that should be considered before trying to use NKT cell agonists as a possible adjuvant approach for LAIV vaccines.The online version contains supplementary material available at 10.1186/s44149-022-00051-x.
1 citations
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TL;DR: The protective role of maternal antibodies against three categories of viruses: viruses that cause severe maternal disease outcomes with mainly indirect consequences to the fetus, those that are vertically transmitted from mother to their infants, and those that cause elevated disease severity among neonates and infants postnatally are discussed.
Abstract: Pregnancy significantly elevates the risk of developing severe viral diseases, which can have a detrimental effect on fetal development and increases maternal mortality. In addition, certain viruses can be transmitted vertically from mother to babies, either in utero, during delivery, or postnatally during breastfeeding, resulting in congenital or neonatal diseases and associated sequelae. While neonates are highly susceptible to viral infections and severe disease outcomes, due to the immaturity of their developing immune system, virus-specific maternal antibodies transferred either trans-placentally or via breast milk provide protection to infants against intestinal, respiratory, or systemic infections, during the first months of life. Thus, maternal prenatal immunization is important not only to protect pregnant women from viral diseases, but also to prevent infection and/or improve disease outcomes for the fetuses and neonates via passively transferred antibodies. In this review, we discuss the protective role of maternal antibodies against three categories of viruses: (i) viruses that cause severe maternal disease outcomes with mainly indirect consequences to the fetus (e.g. SARS-CoV-2, influenza, DENV, filovirus), (ii) those that are vertically transmitted from mother to their infants and cause congenital diseases (e.g. HIV, ZIKV and CMV), and (iii) those that cause elevated disease severity among neonates and infants postnatally (e.g. RSV, Rotavirus, Norovirus, HSV and HBV). Furthermore, we review relevant pre-clinical animal models that can be employed to develop novel immunization strategies against these viruses to enhance protection of pregnant women and their babies.
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TL;DR: In this article , the authors outlined traditional approaches and emerging technologies of virus detection and prevention, and then summarized the latest developments in the bioinformatics methods application in different fields of virus researches, highlighting machine learning and deep learning algorithms to identify factors/categories from complex multidimensional data and uncover novel patterns of virus or disease risk prediction.
Abstract: The pathogenic mechanism of viral infection is a complex process involving viral mutation, viral integration, and various aspects of the interaction between the viral genome and the host. Moreover, the virus mutation will lead to the failure of related vaccines, leading to the increasing of vaccine development costs and difficulties in virus prevention. With the accumulation of various types of data, using bioinformatics methods to mine the potential viral characteristics of the pathogenic process can help virus detection and diagnosis, to take intervention measures to prevent disease development or develop effective antiviral therapies. In this chapter, we first outlined traditional approaches and emerging technologies of virus detection and prevention, and then summarized the latest developments in the bioinformatics methods application in different fields of virus researches. The emergence of artificial intelligence provides advanced analysis techniques for revealing key factors of virus infection and has been widely used in the virology community. In particular, we highlight machine learning and deep learning algorithms to identify factors/categories from complex multidimensional data and uncover novel patterns of virus or disease risk prediction.
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30 May 2023TL;DR: In this paper , the authors evaluated the contribution of ultrasound examinations of the thoracic region of Callithrix sp in diagnosing pneumopathy and found that the combination of air and soft tissues confirms imaging artifacts that may contribute to differentiation of healthy lung tissue from deteriorated lung tissue.
Abstract: Abstract Pulmonary ultrasonography may be useful for early diagnosis and management of respiratory complications. The combination of air and soft tissues confirms imaging artifacts that may contribute to differentiation of healthy lung tissue from deteriorated lung tissue. Although non-human primates are often chosen as research models due to similarity to humans, there is a scarcity of data on the use of pulmonary ultrasound on these individuals. The aim of this study was to evaluate the contribution of ultrasound examinations of the thoracic region of Callithrix sp in diagnosing pneumopathy. Parameters were obtained from 84 Callithix sp of both sexes, aged 1.6 to 15 years and weighing 222 to 684 grams, which were caught within the Mucky Project, in Itu, São Paulo. Thoracic ultrasound examinations were conducted using the LOGIQe-R7 (GE, USA), with a 12 MHz linear transducer, at four points of both antimeres. 18 individuals presented some type of pulmonary alteration. Two of the animals with pulmonary alterations died and then underwent necropsy. Histopathological analysis showed that their lung tissue was compatible with the presence of suppurative bacterial bronchopneumonia. In the light of these cases, pulmonary consolidations diagnosed through thoracic ultrasound examination can be correlated with occurrence of pneumonia.
References
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TL;DR: Wild aquatic bird populations have long been considered the natural reservoir for influenza A viruses with virus transmission from these birds seeding other avian and mammalian hosts, but recent studies in bats have suggested other reservoir species may also exist.
4,155 citations
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TL;DR: The ob gene product, leptin, is an important circulating signal for the regulation of body weight and a series of leptin-alkaline phosphatase (AP) fusion proteins as well as [125I]leptin fusion proteins were generated to identify high affinity leptin-binding sites in the mouse choroid plexus.
3,598 citations
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TL;DR: Known discrepancies in both innate and adaptive immunity are outlined, including balance of leukocyte subsets, defensins, Toll receptors, inducible NO synthase, the NK inhibitory receptor families Ly49 and KIR, FcR, Ig subsets andChemokine and chemokine receptor expression.
Abstract: Mice are the experimental tool of choice for the majority of immunologists and the study of their immune responses has yielded tremendous insight into the workings of the human immune system. However, as 65 million years of evolution might suggest, there are significant differences. Here we outline known discrepancies in both innate and adaptive immunity, including: balance of leukocyte subsets, defensins, Toll receptors, inducible NO synthase, the NK inhibitory receptor families Ly49 and KIR, FcR, Ig subsets, the B cell (BLNK, Btk, and lambda5) and T cell (ZAP70 and common gamma-chain) signaling pathway components, Thy-1, gammadelta T cells, cytokines and cytokine receptors, Th1/Th2 differentiation, costimulatory molecule expression and function, Ag-presenting function of endothelial cells, and chemokine and chemokine receptor expression. We also provide examples, such as multiple sclerosis and delayed-type hypersensitivity, where complex multicomponent processes differ. Such differences should be taken into account when using mice as preclinical models of human disease.
3,098 citations
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TL;DR: The results highlight the enormous annual burden of influenza in the US, with hospitalization costs and lost productivity from missed work days and lost lives comprise the bulk of the economic burden.
1,667 citations
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TL;DR: A structural basis for the hypothesis that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics is demonstrated.
Abstract: Genetic and biologic observations suggest that pigs may serve as “mixing vessels” for the generation of human-avian influenza A virus reassortants, similar to those responsible for the 1957 and 1968 pandemics. Here we demonstrate a structural basis for this hypothesis. Cell surface receptors for both human and avian influenza viruses were identified in the pig trachea, providing a milieu conducive to viral replication and genetic reassortment. Surprisingly, with continued replication, some avian-like swine viruses acquired the ability to recognize human virus receptors, raising the possibility of their direct transmission to human populations. These findings help to explain the emergence of pandemic influenza viruses and support the need for continued surveillance of swine for viruses carrying avian virus genes.
1,010 citations