Pre-Clinical Development of a Recombinant, Replication-Competent Adenovirus Serotype 4 Vector Vaccine Expressing HIV-1 Envelope 1086 Clade C

• DOI: 10.1371/journal.pone.0082380
• Publication Date: 2013-12-03T21:35:49Z
• Authors: Jeff Alexander; Jason Mendy; Lo Vang; Jenny B. Avanzini; Fermin Garduno; Darly J. Manayani; Glenn Ishioka; Peggy Farness; Li-Hua Ping; Ronald Swanstrom; Robert Parks; Hua-Xin Liao; Barton F. Haynes; David C. Montefiori; Celia LaBranche; Jonathan Smith; Marc Gurwith; Tim Mayall
• Keywords: Envelope (radar); Replication

Background There is a well-acknowledged need for an effective AIDS vaccine that protects against HIV-1 infection or limits in vivo viral replication. The objective of these studies to develop replication-competent, vector based on the adenovirus serotype 4 (Ad4) virus expressing envelope (Env) 1086 clade C glycoprotein. Ad4 recombinant vectors Env gp160 (Ad4Env160), gp140 (Ad4Env140), and gp120 (Ad4Env120) were evaluated. Methods generated with full deletion E3 region accommodate env gene sequences. candidates assessed vitro following A549 cells Env-specific protein expression posttranslational transport cell surface as monitored by binding broadly neutralizing antibodies (bNAbs). capacity Ad4Env vaccines induce humoral immunity was evaluated rabbits V1V2-specific antibodies, pseudovirus neutralization. Mice immunized Ad4Env160 IFNγ T responses specific overlapping peptide sets. Results Robust confirmed western blot analysis recognition multiple bNAbs. induced immune recognized V1V2 polypeptide sequences derived from C, A244 AE, gp70 CASE A2 B fusion protein. sera efficiently neutralized tier 1 MW965.26 homologous heterologous 2 pseudoviruses lesser extent. also mice immunization. Conclusions express high levels glycoprotein both cellular thus supporting further development this new platform Phase clinical trials.