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Sex differences in vaccine induced immunity and protection against Mycobacterium tuberculosis
No full textTuberkulose (TB), an der jährlich über eine Million Menschen sterben, betrifft in besonders
hohem Maße Männer. Obwohl das häufigere Auftreten von TB bei Männern aus
epidemiologischer Sicht seit langem bekannt ist, ist das mechanistische Verständnis dieser
Unterschiede relativ neu. Der einzige zugelassene TB-Impfstoff, Bacillus Calmette Guérin
(BCG), weist eine unzureichende Wirksamkeit auf, was die Entwicklung effektiverer Impfstoffe
erforderlich macht. Über Geschlechterunterschiede in der Wirksamkeit von BCG ist jedoch nur
wenig bekannt. In der vorliegenden Arbeit wurde erstmals die fehlende Wirksamkeit von BCG
speziell bei männlichen Tieren im C57BL/6-Mausmodell gezeigt. Zwei rekombinante BCG
Derivate (rBCG) - VPM1002 and BCGΔBCG1419c - konnten hingegen das Überleben nach einer
Mycobacterium tuberculosis (Mtb)-Infektion speziell bei männlichen Mäusen gegenüber der
BCG-Impfung signifikant verlängern und zeigten somit eine deutlich verbesserte Wirksamkeit.
Die Unterschiede in der Überlebensrate zwischen rBCG- und BCG-geimpften Männchen waren
dabei nicht auf ihre Fähigkeit zurückzuführen, die Anzahl der koloniebildenden Einheiten (KBE)
in der Lunge zu reduzieren. Darüber hinaus wurde gezeigt, dass BCGΔBCG1419c, das als
Vertreter der beiden rBCGs verwendet wurde, 90 Tage nach der Impfung die CD8-T-Zell
Antworten im Vergleich zu BCG speziell bei männlichen Mäusen signifikant erhöht - eine
Eigenschaft, die eine signifikante positive Korrelation mit dem Überleben nach Mtb-Belastung
aufwies. Desweiteren wurden signifikante positive Korrelationen zwischen der CD4-T
Zellreaktion am Tag 28 nach der Impfung und der CD8-T-Zellreaktion am Tag 90 nach der
Impfung sowie zwischen der CD4-T- und der B-Zellreaktion am Tag 28 nach der Impfung
festgestellt. Die CD4-T-Zell-Antwort am Tag 28 nach der Impfung zeigte ebenfalls eine
signifikante Korrelation mit dem Überleben nach einer Mtb-Infektion. Schließlich zeigten sich
zwischen den Geschlechtern globale Unterschiede in den CD8-T-Zell Populationen in der Milz
28 Tage nach Impfung, wobei sich unabhängig vom Impfstoff spezifische Cluster zwischen
Weibchen und Männchen unterschieden. Zusammenfassend zeigt diese Studie eine
geschlechtsspezifisch fehlende Wirksamkeit von BCG bei männlichen C57BL/6-Mäusen, und
dass neuere rBCG-Derivate die Wirksamkeit bei Männchen signifikant verbessern. Die
zugrundeliegenden Unterschiede in der Immunantwort nach der Impfung, die mit der
Wirksamkeit des Impfstoffs korrelieren, sowie die Unterschiede in der Immunantwort nach der
Impfung zwischen den Geschlechtern wurden ermittelt. Die Aufklärung, wie
geschlechtsspezifische Unterschiede in den CD8-T-Zell-Antworten die Impfstoffwirksamkeit beeinflussen, sowie die mögliche Rolle von CD4-T-Zellen und B-Zellen für die
geschlechtsspezifische Entwicklung von verschiedenen CD8-T-Zell-Populationen, eröffnet
neue Wege für weiterführende Studien.Tuberculosis (TB), a disease killing over a million people per annum, shows a strong male
preponderance in disease development. Although increased male affliction for TB has long been
known from an epidemiological perspective, the mechanistic understanding of those
differences is relatively recent. The only approved vaccine for TB, Bacillus Calmette Guérin
(BCG), shows high variability in its protective efficacy – necessitating the development of
effective vaccine candidates. However, whether the male-biased susceptibility to TB also
applies to the efficacy of the BCG vaccine, has been scarcely explored. In the current study, a
male specific failure of BCG is demonstrated in the C57BL/6 mouse model. However, two
recombinant derivatives of BCG (rBCGs) - VPM1002 and BCGΔBCG1419c - were found to
ameliorate this male specific vulnerability of BCG by significantly improving survival rates in
males upon Mycobacterium tuberculosis (Mtb) challenge. The disparities in survival between
rBCGs and BCG vaccinated males were not attributable to their ability to reduce lung colony
forming units (CFUs). Further analysis revealed that BCGΔBCG1419c, used as a representative
of VPM1002 and BCGΔBCG1419c, significantly enhances CD8 T cell responses 90 days post
vaccination compared to BCG, specifically in males. This enhancement shows a strong positive
correlation with improved survival following Mtb challenge. In addition, significant positive
correlations were identified between the CD4 T cell response on day 28 post-vaccination and
the CD8 T cell response on day 90 post-vaccination, as well as between the CD4 T and B cell
responses on day 28 post-vaccination. The CD4 T cell response at day 28 post-vaccination also
showed a significant direct correlation with survival following Mtb challenge. Lastly, 28 days
post-vaccination, CD8 T cell populations in the spleen showed distinct global differences
between sexes, with specific clusters varying between males and females, independent of
vaccine type. In summary, the current study identified a male specific failure of BCG in the
C57BL/6 mouse model of TB and the ability of rBCGs to significantly improve the protective
efficacy specifically in males. The underlying differences in post-vaccine immune responses
that correlate with vaccine efficacy, as well as, those differences between sexes were
identified. Elucidating how sex-specific differences in CD8 T cell responses influence vaccine
efficacy, as well as the potential role of CD4 T cells and B cells in the sex-specific development
of different CD8 T cell populations open new avenues for future studies
Sex Differences in Vaccine-Induced Immunity and Protection Against Mycobacterium tuberculosis
No full textTuberculosis (TB) remains a leading global cause of death, with approximately 1.3 million fatalities annually. While males are more susceptible to TB, the underlying immune differences and their impact on vaccine efficacy are not fully understood. In this study, we vaccinated male and female C57BL/6 mice with BCG and 2 recombinant derivatives, VPM1002 and BCGΔBCG1419c, and assessed their protection against Mycobacterium tuberculosis (Mtb) HN878. While all 3 vaccines showed comparable efficacy in females, BCG did not protect males from Mtb-induced death. Instead, recombinant vaccines provided improved protection in males. Vaccination of males with BCGΔBCG1419c, but not BCG, enhanced CD8 T-cell and B-cell recall responses in vaccine-draining lymph nodes, and reduced lung inflammation after Mtb challenge. These findings underscore the impact of sex differences on vaccine efficacy and suggest that future research should consider sex as a biological variable to optimize TB vaccination strategies
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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