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10.1073/pnas.1606050113 http://scihub22266oqcxt.onion/10.1073/pnas.1606050113 C5086995!5086995 !27702895     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=27702895 &cmd=llinks): Failed to open stream: HTTP request failed! 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Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination |pdf=|usr=}}{{27702895 }} gab.com Text Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination JO: Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=27702895 #FOAvip Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. Twit Text FOAVip Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination ????Proc Natl Acad Sci U S A http://www.kidney.de/pget.php?&tw=1&pmid=27702895 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27702895 #FOAvip English Wikipedia <ref>{{Cite pmid|27702895 }}</ref> Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination #MMPMID27702895 Tam HH ; Melo MB ; Kang M ; Pelet JM ; Ruda VM ; Foley MH ; Hu JK ; Kumari S ; Crampton J ; Baldeon AD ; Sanders RW ; Moore JP ; Crotty S ; Langer R ; Anderson DG ; Chakraborty AK ; Irvine DJ Proc Natl Acad Sci U S A 2016[Oct]; 113 (43 ): E6639-E6648 PMID27702895 show ga Natural infections expose the immune system to escalating antigen and inflammation over days to weeks, whereas nonlive vaccines are single bolus events. We explored whether the immune system responds optimally to antigen kinetics most similar to replicating infections, rather than a bolus dose. Using HIV antigens, we found that administering a given total dose of antigen and adjuvant over 1-2 wk through repeated injections or osmotic pumps enhanced humoral responses, with exponentially increasing (exp-inc) dosing profiles eliciting >10-fold increases in antibody production relative to bolus vaccination post prime. Computational modeling of the germinal center response suggested that antigen availability as higher-affinity antibodies evolve enhances antigen capture in lymph nodes. Consistent with these predictions, we found that exp-inc dosing led to prolonged antigen retention in lymph nodes and increased Tfh cell and germinal center B-cell numbers. Thus, regulating the antigen and adjuvant kinetics may enable increased vaccine potency. |AIDS Vaccines/*administration & dosage [MESH] |Adjuvants, Immunologic/administration & dosage [MESH] |Animals [MESH] |Antibodies, Viral/*biosynthesis [MESH] |Antibody Affinity [MESH] |B-Lymphocytes/cytology/*drug effects/immunology [MESH] |CHO Cells [MESH] |Cricetulus [MESH] |Drug Administration Schedule [MESH] |Female [MESH] |Germinal Center/cytology/*drug effects/immunology [MESH] |HEK293 Cells [MESH] |HIV Envelope Protein gp120/*administration & dosage/biosynthesis [MESH] |Humans [MESH] |Immunogenicity, Vaccine [MESH] |Infusion Pumps, Implantable [MESH] |Lipid A/administration & dosage/analogs & derivatives [MESH] |Mice [MESH] |Mice, Inbred C57BL [MESH] |Osmotic Pressure [MESH] |Recombinant Fusion Proteins/administration & dosage/biosynthesis [MESH]Sustained antigen availability during germinal center initiation enhan(epmc).pdf DeepDyve Pubget Overpricing