Adenoviral vectors elicit humoral immunity against variable loop 2 of clade C HIV-1 gp120 via "Antigen Capsid-Incorporation" strategy

• Type of Material: Article
• Authors: Linlin Gu, University of Alabama at Birmingham; Valentina Krendelchtchikova, University of Alabama at Birmingham; Alexandre Krendelchtchikov, University of Alabama at Birmingham; Anitra L. Farrow, University of Alabama at Birmingham; Cynthia Derdeyn, Emory University; Qiana L. Matthews, University of Alabama at Birmingham
• Language: English
• Date: 2016-01-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2015.10.010
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 487
• Start Page: 75
• End Page: 84
• Grant/Funding Information: This work was supported by the National Institutes of Health grant #5R01AI089337-03 (QLM) and National Institutes of Health grant 5T32AI7493-20.; The work generating Z205F Env clone and mAb 6.4 C was supported by the National Institutes of Health grant NIH-R01-58706 (CD).
• Keywords: INFECTION; Life Sciences & Biomedicine; DOUBLE-BLIND; Adenoviral (Ad) vector; Variable loop2 (V2); VACCINE; IgG isotypes; Virology; CHALLENGE; SAFETY; "Antigen Capsid-Incorporation" strategy; Humoral immunity; EFFICACY TRIAL; Science & Technology; PROTECTION; ANTIBODIES; IMMUNOGENICITY; HIV-1 vaccine; ACQUISITION
• Research Categories: Health Sciences, Immunology; Biology, Virology

Abstract

Adenoviral (Ad) vectors in combination with the "Antigen Capsid-Incorporation" strategy have been applied in developing HIV-1 vaccines, due to the vectors[U+05F3] abilities in incorporating and inducing immunity of capsid-incorporated antigens. Variable loop 2 (V2)-specific antibodies were suggested in the RV144 trial to correlate with reduced HIV-1 acquisition, which highlights the importance of developing novel HIV-1 vaccines by targeting the V2 loop. Therefore, the V2 loop of HIV-1 has been incorporated into the Ad capsid protein. We generated adenovirus serotype 5 (Ad5) vectors displaying variable loop 2 (V2) of HIV-1 gp120, with the "Antigen Capsid-Incorporation" strategy. To assess the incorporation capabilities on hexon hypervariable region1 (HVR1) and protein IX (pIX), 20aa or full length (43aa) of V2 and V1V2 (67aa) were incorporated, respectively. Immunizations with the recombinant vectors significantly generated antibodies against both linear and discontinuous V2 epitopes. The immunizations generated durable humoral immunity against V2. This study will lead to more stringent development of various serotypes of adenovirus-vectored V2 vaccine candidates, based on breakthroughs regarding the immunogenicity of V2.