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Systematical assessment of the impact of single spike mutations of SARS-CoV-2 Omicron sub-variants on the neutralization capacity of post-vaccination sera
No full textIntroduction The evolution of novel SARS-CoV-2 variants significantly affects vaccine effectiveness. While these effects can only be studied retrospectively, neutralizing antibody titers are most used as correlates of protection. However, studies assessing neutralizing antibody titers often show heterogeneous data. Methods To address this, we investigated assay variance and identified virus infection time and dose as factors affecting assay robustness. We next measured neutralization against Omicron sub-variants in cohorts with hybrid or vaccine induced immunity, identifying a gradient of immune escape potential. To evaluate the effect of individual mutations on this immune escape potential of Omicron variants, we systematically assessed the effect of each individual mutation specific to Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5. Results We cloned a library of pseudo-viruses expressing spikes with single point mutations, and subjected it to pooled sera from vaccinated hosts, thereby identifying multiple mutations that independently affect neutralization potency. Discussion These data might help to predict antigenic features of novel viral variants carrying these mutations and support the development of broad monoclonal antibodies
MCMV-based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination
No full textAbstract Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality. There remains a medical need for vaccines against these pathogens. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8 + T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing hemagglutinin (HA) of influenza A virus (MCMV HA ) or the spike protein of severe acute respiratory syndrome coronavirus 2 (MCMV S ). A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMV HA -vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to the effects of memory T cells. Conclusively, we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.Abstract Global pandemics caused by influenza or coronaviruses cause severe disruptions to public health and lead to high morbidity and mortality. There remains a medical need for vaccines against these pathogens. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses in which remarkably large populations of antigen-specific CD8 + T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector for expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing hemagglutinin (HA) of influenza A virus (MCMV HA ) or the spike protein of severe acute respiratory syndrome coronavirus 2 (MCMV S ). A single injection of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMV HA -vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to the effects of memory T cells. Conclusively, we show here that MCMV vectors induce not only long-term cellular immunity but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens
Age-related immune responses to COVID-19 vaccines
Full text linkPandemija virusne COVID-19 infekcije je dovela do brojnih hospitalizacija, smrti i kroničnih posljedica infekcije. Premda su kliničke prezentacije u djece i adolescenata u pravilu daleko blaže, teški oblici su prisutni i u ovoj dobnoj skupini, a komplikacije u vidu multisistemskog imunološkog sindroma ili Long-COVIDa su dokumentirane. Cijepljenje, koje je odobreno za djecu iznad 5 godina starosti, pomaže u suzbijanju akutnih i kroničnih posljedica, ali je slabo prihvaćeno u Republici Hrvatskoj. Stoga su potrebni dodatni napori kako bi se javnost upoznala s rizicima koje COVID infekcije nose za djecu, ali i kvalitetno informirala o nuspojavama, rizicima i blagodatima cijepljenja u ovoj dobnoj skupini.The COVID-19 pandemics has led to numerous hospitalizations, deaths, and long-term disabilities. While clinical presentations in children and adolescents are generally milder, severe forms may occur. Moreover, multisystem immune syndrome in children (MIS-C) or Long-COVID complications have been documented in this age group as well. Vaccination is approved for children over 5 years of age and helps to combat acute and chronic
consequences of COVID-19 infection, but is poorly accepted in Croatia. Therefore, additional efforts are needed to make the public aware of the risks that COVID infections pose to children, but also to inform them in a realistic and balanced manner about the side effects, risks and benefits of vaccination in this age group
Komplementacija citomegalovirusnih varijanti in vivo : doktorska disertacija
No full textCilj istraživanja: Višestruke infekcije različitim sojevima citomegalovirusa (CMV)
koreliraju s težom kliničkom slikom i prognozom. Klinička istraživanja nisu mogla
razjasniti jesu li koinfekcije učestale kod neotpornih bolesnika, čija je prognoza lošija,
ili do pogoršanja prognoze dolazi zbog komplementacije među CMV sojevima.
Cilj je ovoga rada definirati uzročno-posljedičnu vezu CMV-replikacije i koinfekcije s
različitim virusnim sojevima in vivo.
Materijal i metode: Singenični miševi su inficirani atenuiranim mutantama mišjeg
CMV-a (MCMV). Kvantitativnim je PCR-om te titracijom infektivnog virusa u
organima uspoređena replikacija MCMV mutanti u prisustvu ili odsustvu virulentnog
virusa. Uloga funkcionalne trans-komplementacije u virusnim in vivo interakcijama
određena je koinfekcijom mutantama koje su eksprimirale Cre-rekombinazu
ili Cre-inducibilni GFP gen. Trans-komplementacija je kvantificirana fluorescentnom
mikroskopijom za GFP te potvrđena PCR-om. Rezultate smo zaključno potvrdili in
situ hibridizacijom specifičnom za različite varijante MCMV-a.
Rezultati: Pri koinfekciji su atenuirane virusne varijante bolje replicirale nego li pri
infekciji pojedinačnim mutantama. Koinfekcija MCMV-om koji je ispoljavao Cre
redovito je dovodila do rekombinacije genoma koinfekcijskog partnera te ekspresije
GFP gena. Genomi različitih mutanti su se nalazili u istim hepatocitima inficiranih
miševa, a većina je stanica inficiranih atenuiranom varijantom bila istovremeno
inficirana virulentnim virusom.
Zaključak: Različite se MCMV varijante nalaze u istim stanicama pri in vivo
koinfekciji, što olakšava virusnu trans-komplementaciju te replikaciju virusnih
varijanti. Stoga, rezultati ukazuju da pri istovremenoj infekciji različitim sojevima
CMV-a dolazi do njihove komplementacije, što pogoršava kliničku sliku i prognozu.Aim: Multiple cytomegalovirus (CMV) strain infections correlate with more severe clinical outcomes. Clinical studies could not clarify whether the resistance to CMV defines the number of CMV strains in a patient, or whether viral complemenation may aggravate the prognosis. This study will define the cause-effect relationship between infections by multiple viral strains and cytomegalovirus in vivo growth.
Materials and Methods: Singenic mice were infected with attenuated mutants of the mouse cytomegalovirus (MCMV). We compared the growth of attenuated MCMVs in the presence or absence of virulent virus by real-time PCR and infectious virus titration. The role of trans-complementation in MCMV strain interactions in vivo was assessed using MCMV mutants expressing Cre-recombinase or a Cre-inducible GFP gene. Fluorescent microscopy for GFP expression was used to quantify transcomplemenation and results were confirmed by PCR. The relevance of complementation for virus replication was confirmed by in situ hybridization assays specific for different MCMV variants.
Results: Coinfection resulted in better replication of attenuated mutants than single infection. The coinfection with the MCMV expressing Cre-recombinase resulted in regular recombination and expression of the GFP gene by the coinfecting virus. Genomes of multiple MCMV variants were found in the same hepatocytes of coinfected animals, and the majority of the cells infected with the attenuated mutant were at the same time infected with the replication competent MCMV.
Conclusion: Multiple CMV variants are found in the same cells during in vivo coinfection, facilitating functional complementation and replication of viral variants. Thus, the results indicate that coinfection with multiple CMV strains leads to viral complementation, which may worsen the clinical picture and the prognosis
Effects and safety profile of childhood vaccines in the light of the biological basis of the immune response
Full text linkDa bi liječničke preporuke o cjepivima bile kvalitetne, moraju biti temeljene na znanstvenim spoznajama koje liječnik detaljno razumije, jer tek onda može rastumačiti rizike i prednosti cijepljenja medicinskim laicima, razbistriti mitove i djelovati u interesu svojih pacijenata i javnog zdravstva. Ovaj kratki pregled će razmotriti fiziologiju imunog odgovora na cjepiva, razlike u učincima cjepiva i infekcija na organizam i imuni odgovor te pojasniti neke od rizika kojima su izložena cijepljena i necijepljena djeca, kako bi se liječnicima praktičarima olakšala komunikacija s pacijentima i laicima
Reverse mutational scanning of SARS-CoV-2 spike BA.2.86 identifies epitopes contributing to immune escape from polyclonal sera
No full textAbstract The recently detected Omicron BA.2.86 lineage contains more than 30 amino acid mutations relative to BA.2. BA.2.86 and its JN.1 derivative evade neutralization by serum antibodies of fully vaccinated individuals. In this study, we elucidate epitopes driving the immune escape of BA.2.86 and JN.1 via pseudovirus neutralization. Here we generate 33 BA.2.86 mutants, each reverting a single mutation back to BA.2. We use this library in an approach that we call reverse mutational scanning to define distinct neutralization titers against each epitope. Mutations within the receptor binding domain at K356T, V483Δ, and to a lesser extent N460K, A484K, and F486P enhance immune escape. Interestingly, 16insMPLF within the spike N-terminal domain and P621S within S1/S2 also significantly contribute to antibody escape of BA.2.86. Upon XBB.1.5 booster vaccination, neutralization titers against JN.1 and BA.2.86 improve considerably, and residual immune escape is driven by 16insMPLF, N460K, E554K, and to a lesser extent P621S, and A484K
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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