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Lactobacilli expressing broadly neutralizing nanobodies against HIV-1 as potential vectors for HIV-1 prophylaxis?

  • 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-1Bal, 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.

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Verfasserangaben:Sarah Kalusche, Kanika VanshyllaORCiD, Franziska Kleipass, Henning GruellORCiDGND, Barbara Müller, Zhu Zeng, Kathrin Koch, Stefan Stein, Harold Marcotte, Florian Klein, Ursula Dietrich
URN:urn:nbn:de:hebis:30:3-572263
DOI:https://doi.org/10.3390/vaccines8040758
ISSN:2076-393X
Pubmed-Id:https://pubmed.ncbi.nlm.nih.gov/33322227
Titel des übergeordneten Werkes (Deutsch):Vaccines
Verlag:MDPI
Verlagsort:Basel
Dokumentart:Wissenschaftlicher Artikel
Sprache:Englisch
Datum der Veröffentlichung (online):13.12.2020
Datum der Erstveröffentlichung:13.12.2020
Veröffentlichende Institution:Universitätsbibliothek Johann Christian Senckenberg
Datum der Freischaltung:11.01.2021
Freies Schlagwort / Tag:HIV-1; Lactobacillus; VHH; humanized mouse model; nanobodies; neutralization; passive immunization; prophylactic vaccine; vector
Jahrgang:8
Ausgabe / Heft:Article 758
Seitenzahl:21
HeBIS-PPN:476178363
Institute:Medizin / Medizin
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
DDC-Klassifikation:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Sammlungen:Universitätspublikationen
Lizenz (Deutsch):License LogoCreative Commons - Namensnennung 4.0