Universität zu Köln

Fischinger, Stephanie ORCID: 0000-0003-2307-3379, Cizmeci, Deniz ORCID: 0000-0003-3231-7726, Deng, Davy ORCID: 0000-0001-5310-5883, Grant, Shannon P., Frahm, Nicole, McElrath, Julie, Fuchs, Jonathan ORCID: 0000-0002-1013-5107, Bart, Pierre-Alexandre, Pantaleo, Giuseppe, Keefer, Michael, Hahn, William O., Rouphael, Nadine, Churchyard, Gavin, Moodie, Zoe, Donastorg, Yeycy, Streeck, Hendrik and Alter, Galit (2021). Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials. PLoS Pathog., 17 (11). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7374

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Abstract

Despite the advent of long-acting anti-retroviral therapy able to control and prevent infection, a preventative vaccine remains a global priority for the elimination of HIV. The moderately protective RV144 vaccine trial suggested functional IgG1 and IgG3 antibodies were a potential correlate of protection, but the RV144-inspired HVTN702 validation trial failed to demonstrate efficacy despite inducing targeted levels of IgG1/IgG3. Alterations in inserts, and antigens, adjuvant, and regimen also resulted in vaccine induced target quantitative levels of the immune correlates, but drove qualitative changes to the humoral immune response, pointing to the urgent need to define the influence of vaccine strategies on shaping antibody quality, not just quantity. Thus, defining how distinct prime/boost approaches tune long-lived functional antibodies represents an important goal in vaccine development. Here, we compared vaccine responses in Phase I and II studies in humans utilizing various combinations of DNA/vector, vector/vector and DNA/protein HIV vaccines. We found that adenoviral vector immunization, compared to pox-viral vectors, resulted in the most potent IgG1 and IgG3 responses, linked to highly functional antibody activity, including assisting NK cell related functions. Minimal differences were observed in the durability of the functional humoral immune response across vaccine regimens, except for antibody dependent phagocytic function, which persisted for longer periods in the DNA/rAd5 and rAd35/rAd5 regimen, likely driven by higher IgG1 levels. Collectively, these findings suggest adenoviral vectors drive superior antibody quality and durability that could inform future clinical vaccine studies.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Fischinger, Stephanie UNSPECIFIED orcid.org/0000-0003-2307-3379 UNSPECIFIED Cizmeci, Deniz UNSPECIFIED orcid.org/0000-0003-3231-7726 UNSPECIFIED Deng, Davy UNSPECIFIED orcid.org/0000-0001-5310-5883 UNSPECIFIED Grant, Shannon P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frahm, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED McElrath, Julie UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuchs, Jonathan UNSPECIFIED orcid.org/0000-0002-1013-5107 UNSPECIFIED Bart, Pierre-Alexandre UNSPECIFIED UNSPECIFIED UNSPECIFIED Pantaleo, Giuseppe UNSPECIFIED UNSPECIFIED UNSPECIFIED Keefer, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Hahn, William O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rouphael, Nadine UNSPECIFIED UNSPECIFIED UNSPECIFIED Churchyard, Gavin UNSPECIFIED UNSPECIFIED UNSPECIFIED Moodie, Zoe UNSPECIFIED UNSPECIFIED UNSPECIFIED Donastorg, Yeycy UNSPECIFIED UNSPECIFIED UNSPECIFIED Streeck, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Alter, Galit UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-604020
DOI:	10.1371/journal.ppat.1010016
Journal or Publication Title:	PLoS Pathog.
Volume:	17
Number:	11
Date:	2021
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7374
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEUTRALIZING ANTIBODIES; HIGH-THROUGHPUT; RHESUS-MONKEYS; VIRUS; RESPONSES; ALVAC; IMMUNIZATION; ADENOVIRUS; EFFICACY; STRATEGIES Multiple languages Microbiology; Parasitology; Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/60402