{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:53:26Z","timestamp":1790636006716,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Clinical Investigation","issue":"12","funder":[{"DOI":"10.13039\/100000098","name":"NIH Clinical Center","doi-asserted-by":"crossref","award":["R37AI080289"],"award-info":[{"award-number":["R37AI080289"]}],"id":[{"id":"10.13039\/100000098","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,18]]},"abstract":"<jats:p>The RV144 HIV-1 vaccine trial results showed moderate reduction in viral infections among vaccinees as well as induction of antibody-dependent cellular cytotoxicity and vaccine-specific IgG and IgG3 responses directed at variable loop regions 1 and 2 of the HIV envelope protein. However, with the recent failure of the HVTN 702 clinical trial, comprehensive profiling of humoral immune responses may provide insight for these disappointing results. One of the changes included in the HVTN 702 study was the addition of a late boost, aimed at augmenting peak immunity and durability. The companion vaccine trial RV305 was designed to permit the evaluation of the immunologic impact of late boosting with either the boosting protein antigen alone, the canarypox viral vector ALVAC alone, or a combination of both. Although previous data showed elevated levels of IgG antibodies in both boosting arms, regardless of ALVAC-HIV vector incorporation, the effect on shaping antibody effector function remains unclear. Thus, here we analyzed the antibody and functional profile induced by RV305 boosting regimens and found that although IgG1 levels increased in both arms that included protein boosting, IgG3 levels were reduced compared with the original RV144 vaccine strategy. Most functional responses increased upon protein boosting, regardless of the viral vector-priming agent incorporation. These data suggest that the addition of a late protein boost alone is sufficient to increase functionally potent vaccine-specific antibodies previously associated with reduced risk of infection with HIV.<\/jats:p>","DOI":"10.1172\/jci.insight.135057","type":"journal-article","created":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T11:01:33Z","timestamp":1592391693000},"source":"Crossref","is-referenced-by-count":13,"title":["Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response"],"prefix":"10.1172","volume":"5","author":[{"given":"Stephanie","family":"Fischinger","sequence":"first","affiliation":[{"name":"Ragon Institute of MGH, Harvard and MGH, Cambridge, Massachusetts, USA."},{"name":"Institut f\u00fcr HIV Forschung, Universit\u00e4t Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sally","family":"Shin","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, Harvard and MGH, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5006-3067","authenticated-orcid":true,"given":"Carolyn M.","family":"Boudreau","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, Harvard and MGH, Cambridge, Massachusetts, USA."},{"name":"PhD Program in Virology, Harvard University, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Supachai","family":"Rerks-Ngarm","sequence":"additional","affiliation":[{"name":"Department of Disease Control, Ministry of Public Health, Nonthaburi, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punnee","family":"Pitisuttithum","sequence":"additional","affiliation":[{"name":"Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorachai","family":"Nitayaphan","sequence":"additional","affiliation":[{"name":"Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome H.","family":"Kim","sequence":"additional","affiliation":[{"name":"International Vaccine Institute, Seoul, South Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-9649","authenticated-orcid":true,"given":"Merlin L.","family":"Robb","sequence":"additional","affiliation":[{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA."},{"name":"US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5882-5548","authenticated-orcid":true,"given":"Nelson L.","family":"Michael","sequence":"additional","affiliation":[{"name":"US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"O\u2019Connell","sequence":"additional","affiliation":[{"name":"Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand."},{"name":"US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6378-6288","authenticated-orcid":true,"given":"Sandhya","family":"Vasan","sequence":"additional","affiliation":[{"name":"Armed Forces Research Institute of Medical Sciences, Bangkok, Thailand."},{"name":"Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Maryland, USA."},{"name":"US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0335-6390","authenticated-orcid":true,"given":"Hendrik","family":"Streeck","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr HIV Forschung, Universit\u00e4t Duisburg-Essen, Essen, Germany."},{"name":"Institute of Virology, Universit\u00e4tsklinikum Bonn, Bonn, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-9215","authenticated-orcid":true,"given":"Galit","family":"Alter","sequence":"additional","affiliation":[{"name":"Ragon Institute of MGH, Harvard and MGH, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2020,6,18]]},"reference":[{"issue":"1","key":"B1","doi-asserted-by":"crossref","DOI":"10.4102\/sajhivmed.v19i1.721","article-title":"Barriers to HIV service utilisation by people living with HIV in two provinces of Zimbabwe: Results from 2016 baseline assessment","volume":"19","author":"Tafuma","year":"2018","journal-title":"South Afr J HIV Med"},{"key":"B2"},{"key":"B3","unstructured":"Prevent HIV, Test and Treat All - WHO Support for Country Impact. World Health Organization Web Site. https:\/\/www.who.int\/hiv\/pub\/progressreports\/2016-progress-report\/en\/ Accessed May 18, 2020"},{"issue":"6","key":"B4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.2174\/1570162X113116660051","article-title":"Lessons learned from HIV vaccine clinical efficacy trials","volume":"11","author":"Day","year":"2013","journal-title":"Curr HIV Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0908492"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70088-9"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aac7732"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180720"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007736"},{"key":"B10","unstructured":"[No authors listed]. Experimental HIV Vaccine Regimen Ineffective in Preventing HIV. National Institutes of Health Web Site. https:\/\/www.nih.gov\/news-events\/news-releases\/experimental-hiv-vaccine-regimen-ineffective-preventing-hiv Published February 3, 2020. Accessed May 18, 2020"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1113425"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3007730"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix099"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006182"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2004.08.008"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2008.08.007"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400093"},{"issue":"4","key":"B18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.AID-0019-2014","article-title":"Functions of antibodies","volume":"2","author":"Forthal","year":"2014","journal-title":"Microbiol Spectr"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/01.COH.0000432529.38768.1f"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.01.005"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005315"},{"issue":"20","key":"B22","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01051-18","article-title":"Adjuvant-dependent enhancement of HIV Env-specific antibody responses in infant rhesus macaques","volume":"92","author":"Phillips","year":"2018","journal-title":"J Virol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1172\/JCI129520"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3886"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.09.061"},{"key":"B26","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/156241","article-title":"Structural and computational biology in the design of immunogenic vaccine antigens","volume":"2015","author":"Liljeroos","year":"2015","journal-title":"J Immunol Res"},{"issue":"1\u20132","key":"B27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jim.2012.09.007","article-title":"High-throughput, multiplexed IgG subclassing of antigen-specific antibodies from clinical samples","volume":"386","author":"Brown","year":"2012","journal-title":"J Immunol Methods"},{"issue":"1\u20132","key":"B28","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jim.2010.12.016","article-title":"A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples","volume":"366","author":"Ackerman","year":"2011","journal-title":"J Immunol Methods"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2019.05.006"},{"key":"B30","doi-asserted-by":"crossref","DOI":"10.1016\/j.jim.2019.07.002","article-title":"A high-throughput, bead-based, antigen-specific assay to assess the ability of antibodies to induce complement activation","volume":"473","author":"Fischinger","year":"2019","journal-title":"J Immunol Methods"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0441-3"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.08.072"},{"issue":"165","key":"B33","doi-asserted-by":"crossref","DOI":"10.1126\/scisignal.2001338","article-title":"In vivo systems analysis identifies spatial and temporal aspects of the modulation of TNF-\u03b1-induced apoptosis and proliferation by MAPKs","volume":"4","author":"Lau","year":"2011","journal-title":"Sci Signal"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/135057\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T12:13:55Z","timestamp":1779192835000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/135057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,18]]},"references-count":33,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,6,18]]},"published-print":{"date-parts":[[2020,6,18]]}},"alternative-id":["10.1172\/jci.insight.135057"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.135057","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,18]]},"article-number":"e135057"}}