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Title: Protein-based, but not viral vector alone, HIV vaccine boosting drives an IgG1-biased polyfunctional humoral immune response
Authors: Stephanie Fischinger
Sally Shin
Carolyn M. Boudreau
Margaret Ackerman
Supachai Rerks-Ngarm
Punnee Pitisuttithum
Sorachai Nitayaphan
Jerome H. Kim
Merlin L. Robb
Nelson L. Michael
Robert J. O'Connell
Sandhya Vasan
Hendrik Streeck
Galit Alter
International Vaccine Institute, Seoul
Universitäts-Klinikum Bonn und Medizinische Fakultät
Thayer School of Engineering at Dartmouth
Armed Forces Research Institute of Medical Sciences, Thailand
Thailand Ministry of Public Health
Universität Duisburg-Essen
Walter Reed Army Institute of Research
Mahidol University
Harvard University
Harvard and MGH
Keywords: Medicine
Issue Date: 18-Jun-2020
Citation: JCI insight. Vol.5, No.12 (2020)
Abstract: 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.
ISSN: 23793708
Appears in Collections:Scopus 2020

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