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

• 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
• Journal Title: Virology
• Volume: Volume 487
• Publisher: Elsevier | 2016-01-01, Pages 75-84
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.virol.2015.10.010
• Subjects: Biology, Virology; Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Virology; HIV-1 vaccine; Adenoviral (Ad) vector; "Antigen Capsid-Incorporation" strategy; Variable loop2 (V2); Humoral immunity; IgG isotypes; EFFICACY TRIAL; DOUBLE-BLIND; VACCINE; ANTIBODIES; IMMUNOGENICITY; PROTECTION; ACQUISITION; CHALLENGE; INFECTION; SAFETY

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.