Universität zu Köln

Vieillard, Vincent, Combadiere, Behazine, Tubiana, Roland, Launay, Odile, Pialoux, Gilles, Cotte, Laurent, Girard, Pierre-Marie, Simon, Anne, Dudoit, Yasmine, Reynes, Jacques, Rockstroh, Juergen, Garcia, Felipe, Gatell, Jose, Devidas, Alain, Yazdanpanah, Yazdan, Weiss, Laurence, Faetkenheuer, Gerd, Autran, Brigitte, Joyeux, Delphine, Gharakhanian, Shahin, Debre, Patrice and Katlama, Christine (2019). HIV therapeutic vaccine enhances non-exhausted CD4(+) T cells in a randomised phase 2 trial. npj Vaccines, 4. LONDON: SPRINGERNATURE. ISSN 2059-0105

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Abstract

VAC-3S is a therapeutic vaccine comprising a highly conserved HIV-gp41 motif coupled with the CRM197 carrier protein. High levels of anti-3S antibodies (Abs) have been associated with improved protection of CD4(+) T-cell survival. A previous phase 1 study demonstrated the safety of VAC-3S. This multicentre, randomised, double-blind, placebo-controlled phase 2 clinical trial enroled between January 2014 and March 2015 HIV-1-infected patients under ART with plasma HIV RNA levels below 50 copies/mL and CD4 counts between 200 and 500 cells/mu L. Participants were immunised with 16, 32, or 64 mu g of VAC-3S, and compared to placebo. The primary outcome was immunogenicity assessed by changes from baseline of anti-3S Abs levels at week 12. Secondary outcomes included adverse events and the course of plasma HIV RNA level, CD4 count, CD4/CD8 ratio, inflammation and immune checkpoints from week 0 to week 48. Vaccination was well tolerated with no serious adverse events and induced a significant increase in anti-3S Ab response in vaccinated patients (p < 0.0001), compared to placebo. In high responders, the robust increased of CD4 count was associated with a significant and sustained reduction of PD-1 expression on CD4(+) T cells through week 48 (variance p = 0.0017). PD-1 expression was correlated with level of anti-3S Abs (p = 0.0092, r = -0.68) and expression of NKp44L (p < 0.0001; r = 0.54) in CD4(+) T cells. Our findings regarding the increase of non-exhausted CD4(+) T cells have potentially important application in personalised HIV vaccination for HIV-infected patients with high level of PD-1 to improve their T-cell immune function.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vieillard, Vincent UNSPECIFIED UNSPECIFIED UNSPECIFIED Combadiere, Behazine UNSPECIFIED UNSPECIFIED UNSPECIFIED Tubiana, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Launay, Odile UNSPECIFIED UNSPECIFIED UNSPECIFIED Pialoux, Gilles UNSPECIFIED UNSPECIFIED UNSPECIFIED Cotte, Laurent UNSPECIFIED UNSPECIFIED UNSPECIFIED Girard, Pierre-Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Dudoit, Yasmine UNSPECIFIED UNSPECIFIED UNSPECIFIED Reynes, Jacques UNSPECIFIED UNSPECIFIED UNSPECIFIED Rockstroh, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Garcia, Felipe UNSPECIFIED UNSPECIFIED UNSPECIFIED Gatell, Jose UNSPECIFIED UNSPECIFIED UNSPECIFIED Devidas, Alain UNSPECIFIED UNSPECIFIED UNSPECIFIED Yazdanpanah, Yazdan UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiss, Laurence UNSPECIFIED UNSPECIFIED UNSPECIFIED Faetkenheuer, Gerd UNSPECIFIED UNSPECIFIED UNSPECIFIED Autran, Brigitte UNSPECIFIED UNSPECIFIED UNSPECIFIED Joyeux, Delphine UNSPECIFIED UNSPECIFIED UNSPECIFIED Gharakhanian, Shahin UNSPECIFIED UNSPECIFIED UNSPECIFIED Debre, Patrice UNSPECIFIED UNSPECIFIED UNSPECIFIED Katlama, Christine UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-138214
DOI:	10.1038/s41541-019-0117-5
Journal or Publication Title:	npj Vaccines
Volume:	4
Date:	2019
Publisher:	SPRINGERNATURE
Place of Publication:	LONDON
ISSN:	2059-0105
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTIRETROVIRAL THERAPY; NKP44L EXPRESSION; CYTOTOXICITY; MECHANISMS; INFECTION; DEPLETION; RESPONSES; IMPACT Multiple languages Immunology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13821