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      Influenza vaccine–induced human bone marrow plasma cells decline within a year after vaccination

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          Abstract

          A universal vaccine against influenza would ideally generate protective immune responses that are not only broadly reactive against multiple influenza strains, but also long-lasting. Because long-term serum antibody levels are maintained by bone marrow plasma cells (BMPC), we investigated the production and maintenance of these cells after influenza vaccination. We found increased numbers of influenza-specific BMPC four weeks after immunization with the seasonal inactivated influenza vaccine, but numbers returned to near their pre-vaccination levels after one year. This decline was driven by the loss of BMPC induced by the vaccine, while pre-existing BMPC were maintained. Our results suggest that most BMPC generated by influenza vaccination in adults are short-lived. Designing strategies to enhance their persistence will be a key challenge for the next generation of influenza vaccines.

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          Most cited references29

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          FLASH: fast length adjustment of short reads to improve genome assemblies.

          Next-generation sequencing technologies generate very large numbers of short reads. Even with very deep genome coverage, short read lengths cause problems in de novo assemblies. The use of paired-end libraries with a fragment size shorter than twice the read length provides an opportunity to generate much longer reads by overlapping and merging read pairs before assembling a genome. We present FLASH, a fast computational tool to extend the length of short reads by overlapping paired-end reads from fragment libraries that are sufficiently short. We tested the correctness of the tool on one million simulated read pairs, and we then applied it as a pre-processor for genome assemblies of Illumina reads from the bacterium Staphylococcus aureus and human chromosome 14. FLASH correctly extended and merged reads >99% of the time on simulated reads with an error rate of <1%. With adequately set parameters, FLASH correctly merged reads over 90% of the time even when the reads contained up to 5% errors. When FLASH was used to extend reads prior to assembly, the resulting assemblies had substantially greater N50 lengths for both contigs and scaffolds. The FLASH system is implemented in C and is freely available as open-source code at http://www.cbcb.umd.edu/software/flash. t.magoc@gmail.com.
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            Humoral immunity due to long-lived plasma cells.

            Conventional models suggest that long-term antibody responses are maintained by the continuous differentiation of memory B cells into antibody-secreting plasma cells. This is based on the notion that plasma cells are short-lived and need to be continually replenished by memory B cells. We examined the issue of plasma cell longevity by following the persistence of LCMV-specific antibody and plasma cell numbers after in vivo depletion of memory B cells and by adoptive transfer of virus-specific plasma cells into naive mice. The results show that a substantial fraction of plasma cells can survive and continue to secrete antibody for extended periods of time (>1 year) in the absence of any detectable memory B cells. This study documents the existence of long-lived plasma cells and demonstrates a new mechanism by which humoral immunity is maintained.
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              Duration of antiviral immunity after smallpox vaccination.

              Although naturally occurring smallpox was eliminated through the efforts of the World Health Organization Global Eradication Program, it remains possible that smallpox could be intentionally released. Here we examine the magnitude and duration of antiviral immunity induced by one or more smallpox vaccinations. We found that more than 90% of volunteers vaccinated 25-75 years ago still maintain substantial humoral or cellular immunity (or both) against vaccinia, the virus used to vaccinate against smallpox. Antiviral antibody responses remained stable between 1-75 years after vaccination, whereas antiviral T-cell responses declined slowly, with a half-life of 8-15 years. If these levels of immunity are considered to be at least partially protective, then the morbidity and mortality associated with an intentional smallpox outbreak would be substantially reduced because of pre-existing immunity in a large number of previously vaccinated individuals.
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                Author and article information

                Journal
                Science
                Science
                American Association for the Advancement of Science (AAAS)
                0036-8075
                1095-9203
                August 13 2020
                : eaaz8432
                Affiliations
                [1 ]Emory Vaccine Center and Department of Microbiology and Immunology, Emory University, Atlanta, GA, USA.
                [2 ]Emory-UGA Center of Excellence of Influenza Research and Surveillance (CEIRS), Atlanta GA, USA.
                [3 ]Department of Pathology, Stanford University, Stanford, CA, USA.
                [4 ]Cell Signaling Technology, Inc., Danvers, MA, USA.
                [5 ]Department of Hematology and Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.
                [6 ]Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, GA, USA.
                [7 ]Division of Infectious Diseases, School of Medicine, Emory University, Atlanta, GA, USA.
                Article
                10.1126/science.aaz8432
                32792465
                fe272109-eba0-4c34-9416-4188e2e1fd80
                © 2020
                History

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