Universität zu Köln

Kalusche, Sarah, Vanshylla, Kanika, Kleipass, Franziska, Gruell, Henning, Muller, Barbara ORCID: 0000-0001-5726-5585, Zeng, Zhu, Koch, Kathrin, Stein, Stefan ORCID: 0000-0003-1473-9706, Marcotte, Harold, Klein, Florian and Dietrich, Ursula (2020). Lactobacilli Expressing Broadly Neutralizing Nanobodies against HIV-1 as Potential Vectors for HIV-1 Prophylaxis? Vaccines, 8 (4). BASEL: MDPI. ISSN 2076-393X

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Abstract

In the absence of an active prophylactic vaccine against HIV-1, passively administered, broadly neutralizing antibodies (bnAbs) identified in some chronically infected persons were shown to prevent HIV-1 infection in animal models. However, passive administration of bnAbs may not be suited to prevent sexual HIV-1 transmission in high-risk cohorts, as a continuous high level of active bnAbs may be difficult to achieve at the primary site of sexual transmission, the human vagina with its acidic pH. Therefore, we used Lactobacillus, a natural commensal in the healthy vaginal microbiome, to express bn nanobodies (VHH) against HIV-1 that we reported previously. After demonstrating that recombinant VHHA6 expressed in E. coli was able to protect humanized mice from mucosal infection by HIV-1(Bal), we expressed VHHA6 in a soluble or in a cell-wall-anchored form in Lactobacillus rhamnosus DSM14870. This strain is already clinically applied for treatment of bacterial vaginosis. Both forms of VHHA6 neutralized a set of primary epidemiologically relevant HIV-1 strains in vitro. Furthermore, VHHA6 was still active at an acidic pH. Thus, lactobacilli expressing bn VHH potentially represent an attractive vector for the passive immunization of women in cohorts at high risk of HIV-1 transmission.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kalusche, Sarah UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanshylla, Kanika UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleipass, Franziska UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruell, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Muller, Barbara UNSPECIFIED orcid.org/0000-0001-5726-5585 UNSPECIFIED Zeng, Zhu UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Stein, Stefan UNSPECIFIED orcid.org/0000-0003-1473-9706 UNSPECIFIED Marcotte, Harold UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Dietrich, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-309531
DOI:	10.3390/vaccines8040758
Journal or Publication Title:	Vaccines
Volume:	8
Number:	4
Date:	2020
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2076-393X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANTIBODY FRAGMENTS; DOMAIN; TRANSMISSION; PROTECTION; VRC01; COMBINATION; INFECTION; ROTAVIRUS; ALX-0081; JENSENII Multiple languages Immunology; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/30953