Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses

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Fältnamn	Indikatorer	Metadata
000		04129naa a2200637 4500
001		oai:DiVA.org:su-181099
003		SwePub
008		200429s2020 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:prod.swepub.kib.ki.se:143417053
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-1810992 URI
024	7	a https://doi.org/10.1084/jem.201911552 DOI
024	7	a http://kipublications.ki.se/Default.aspx?queryparsed=id:1434170532 URI
040		a (SwePub)sud (SwePub)ki
041		a engb eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Phad, Ganesh E.4 aut
245	1 0	a Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses
264		c 2019-11-08
264	1	b Rockefeller University Press,c 2020
338		a print2 rdacarrier
520		a Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with Glade C NFL trimers and identified 180 unique Ab lineages from similar to 1,000 single-sorted Envspecific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRO, especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Mikrobiologi inom det medicinska området0 (SwePub)301092 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Microbiology in the medical area0 (SwePub)301092 hsv//eng
650	7	a NATURVETENSKAPx Biologi0 (SwePub)1062 hsv//swe
650	7	a NATURAL SCIENCESx Biological Sciences0 (SwePub)1062 hsv//eng
700	1	a Pushparaj, Pradeepa4 aut
700	1	a Tran, Karen4 aut
700	1	a Dubrovskaya, Viktoriya4 aut
700	1	a Adori, Monikau Karolinska Institutet4 aut
700	1	a Martinez-Murillo, Paola4 aut
700	1	a Bernat, Nestor Vazquez4 aut
700	1	a Singh, Suruchiu Karolinska Institutet4 aut
700	1	a Dionne, Gilman4 aut
700	1	a O'Dell, Sijy4 aut
700	1	a Bhullar, Komalu Karolinska Institutet4 aut
700	1	a Narang, Sanjana4 aut
700	1	a Sorini, Chiarau Karolinska Institutet4 aut
700	1	a Villablanca, Eduardo J.u Karolinska Institutet4 aut
700	1	a Sundling, Christopheru Karolinska Institutet4 aut
700	1	a Murrell, Benjaminu Karolinska Institutet4 aut
700	1	a Mascola, John R.4 aut
700	1	a Shapiro, Lawrence4 aut
700	1	a Pancera, Marie4 aut
700	1	a Martin, Marcelu Karolinska Institutet,Stockholms universitet,Institutionen för biokemi och biofysik4 aut0 (Swepub:su)marcm
700	1	a Corcoran, Martin4 aut
700	1	a Wyatt, Richard T.4 aut
700	1	a Hedestam, Gunilla B. Karlsson4 aut
710	2	a Karolinska Institutetb Institutionen för biokemi och biofysik4 org
773	0	t Journal of Experimental Medicined : Rockefeller University Pressg 217:2q 217:2x 0022-1007x 1540-9538
856	4	u https://doi.org/10.1084/jem.20191155y Fulltext
856	4	u https://rupress.org/jem/article-pdf/217/2/e20191155/1175855/jem_20191155.pdf
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-181099
856	4 8	u https://doi.org/10.1084/jem.20191155
856	4 8	u http://kipublications.ki.se/Default.aspx?queryparsed=id:143417053

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