Cross-clade neutralizing antibodies against HIV-1 induced in rabbits by focusing the immune response on a neutralizing epitope

• Published in: Virology (New York, N.Y.) Vol. 392; no. 1; pp. 82 - 93
• Main Authors: Zolla-Pazner, Susan, Cohen, Sandra, Pinter, Abraham, Krachmarov, Chavdar, Wrin, Terri, Wang, Shixia, Lu, Shan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.09.2009
• Subjects: 60 APPLIED LIFE SCIENCES; AIDS Vaccines - genetics; AIDS Vaccines - immunology; AIDS VIRUS; Amino Acid Sequence; ANIMALS; ANTIBODIES; DNA; DNA, Viral - genetics; Epitopes; Epitopes - genetics; Female; Glycoprotein gp120; gp120; HIV Antibodies - biosynthesis; HIV Envelope Protein gp120 - genetics; HIV Envelope Protein gp120 - immunology; HIV-1; HIV-1 - classification; HIV-1 - genetics; HIV-1 - immunology; Human immunodeficiency virus 1; Humans; Immune response; IMMUNE SERUMS; Immunization; Immunization, Secondary; Infectious Disease; MAMMALS; MICROORGANISMS; Molecular Sequence Data; Neutralization Tests; Neutralizing antibodies; NUCLEIC ACIDS; ORGANIC COMPOUNDS; PARASITES; Peptide Fragments - genetics; Peptide Fragments - immunology; PROTEINS; Pseudovirus; RABBITS; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; V3 loop; Vaccine; VACCINES; VERTEBRATES; VIRUSES; HIV-1; Immunization; V3 loop; Neutralizing antibodies; Pseudovirus; gp120; Vaccine
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2009.05.039

Abstract Studies were performed to induce cross-clade neutralizing antibodies (Abs) by testing various combinations of prime and boost constructs that focus the immune response on structurally-conserved epitopes in the V3 loop of HIV-1 gp120. Rabbits were immunized with gp120 DNA containing a V3 loop characterized by the GPGR motif at its tip, and/or with gp120 DNA with a V3 loop carrying the GPGQ motif. Priming was followed by boosts with V3-fusion proteins (V3-FPs) carrying the V3 sequence from a subtype B virus (GPGR motif), and/or with V3 sequences from subtypes A and C (GPGQ motif). The broadest and most consistent neutralizing responses were generated when using a clade C gp120 DNA prime and with the V3B -FP boost. Immune sera displayed neutralizing activity in three assays against pseudoviruses and primary isolates from subtypes A, AG, B, C, and D. Polyclonal Abs in the immune rabbit sera neutralized viruses that were not neutralized by pools of human anti-V3 monoclonal Abs. Greater than 80% of the neutralizing Abs were specific for V3, showing that the immune response could be focused on a neutralizing epitope and that vaccine-induced anti-V3 Abs have cross-clade neutralizing activity.