bodies. The altered mode of heavy chain recognition allows the VH1-46 derived antibodies to accommodate light chain CDR3s of different lengths. Cross-donor phylogenetic analysis showed that the VH1-46 derived antibodies from 2 donors evolved similarly and indicated that the VH1-46 antibodies form a class. Conclusions: Our studies show how antibodies of the VH1-46 class achieve CD4 mimicry, expand the range of known struc- tural solutions that permit such heavy-chain mimicry, and reveal how small differences in germline (e.g. between VH1-2 and VH1-46) can impact mature antibody recognition. P10.12 Longitudinal Antibody Development in SHIV AD8 Infected Non-Human Primate Zizhang Sheng 1 , Joseph R. Francica 2 , Yoshiaki Nishimura 3 , Stephen D. Schmidt 2 , Rebecca Lynch 2 , Sam Darko 2 , Zhenhai Zhang 1,4 , Frederick Jaeger 5 , Munir Alam 5 , Daniel Douek 2 , John R. Mascola 2 , Malcolm A. Martin 3 , Robert A. Seder 2 , Lawrence Shapiro 1 1 Columbia University, Department of Biochemistry and Mole- cular Biophysics, New York, NY, United States, 2 National In- stitutes of Health, Vaccine Research Center, Bethesda, MD, United States, 3 National Institute of Allergy and Infectious Diseases, National Institutes of Health, Laboratory of Molecular Microbiology, Bethesda, MD, United States, 4 Southern Medical University, Division of Nephrology, Nanfang Hospital, Guangzhou, China, 5 Duke University Medical Center, Duke Human Vaccine Institute, Durham, NC, United States Background: SHIV infected non-human primate (NHP) is an important system to study antibody development relevant to HIV-1 infection in humans. CCR5-tropic SHIV AD8-EO is a clade B virus that has a tier 2 neutralization phenotype and can induce broadly neutralizing antibodies. However, the developmental characteristics of SHIV AD8 elicited NHP antibodies are unclear. Methods: Four of eight SHIV AD8 infected Rhesus macaques developed cross-reactive antibodies (good neutralizers) and others showed weak Tier1 virus neutralizing activity (poor neutralizers). Peripheral memory B cells from all animals at four time frames (6–8, 26–32, 52–54, and 91–110 weeks) were sorted into gp120 reactive (gp120 + ) and non-reactive B cells (gp120-). Antibody heavy chains were then sequenced by 454-pyr- osequencing. Germline V gene was assigned for each antibody sequence using a newly characterized NHP heavy chain V gene database. Somatic hypermutation level and CDRH3 length were then calculated using an in-house bioinformatics pipeline. Results: Compared with gp120- B cells, VH gene composition analysis of gp120 + B cells showed enriched VH3-J (human ortholog VH3-23), VH4-D (human VH4-B) and VH4-A (human VH4/OR15-8) antibodies from good neutralizers. The somatic hypermutation level of gp120 + B cell antibodies increased gradually from *4% at week6 to *10% at week 110. In gp120 + B cells of six animals, more frequent usage of antibodies with CDRH3 *20aa in length is observed. In animal DCF1 (good neutralizer), more than ten long CDRH3 ( >= 28aa) an- tibody lineages were elicited at early time points and some continued expanding through week 108 post infection. Conclusions: SHIV AD8 infection preferably elicited certain VDJ-recombined antibodies. The SHIV AD8 infected NHP sys- tem captures characteristics of antibody development in HIV-1 infected humans, such as longitudinal antibody maturation and elicitation of long CDRH3 antibodies. This supports the idea that SHIV AD8 infected NHP provides a good model for the study of HIV antibody development. P10.13 LB A Novel Trimeric V1V2-Scaffold Immunogen Induces V2q-Specific Antibody Responses Xunqing Jiang 1 , Max Totrov 2 , Constance Williams 3 , Wei Li 4 , Shan Lu 4 , Shixia Wang 4 , Susan Zolla-Pazner 3 , Xiang-Peng Kong 1 1 NYU School of Medicine, Department of Biochemistry and Molecular Pharmacology, New York, NY, United States, 2 Molsoft LLC, San Diego, CA, United States, 3 NYU School of Medicine, Department of Pathology, New York, NY, United States, 4 University of Massachusetts Medical School, Depart- ment of Medicine, Worcester, MA, United States Background: Data from the RV144 vaccine clinical trial re- vealed that high levels of antibodies to the first and second variable regions (V1V2) of gp120 were correlated with the modest protection from HIV-1 infection; thus V1V2 is a po- tential target for HIV/AIDS vaccine development. V1V2 is known to harbor three distinct epitope types including V2q de- fined by quaternary broadly neutralizing mAbs such as PG9/ PG16, V2p defined by the RV144 mAbs CH58/CH59, and V2i defined by a panel of mAbs, such as 697-D, targeting a region overlapping the V1V2 integrin-binding site. It is highly desirable to develop immunogens that can induce antibody responses specific for these epitope types. Methods: We engineered a trimeric V1V2 (ZM53 sequence) immunogen that was designed to mimic Env conformation by inserting it into a trimeric scaffold (PDB ID 2J9C). We produced this immunogen in 293 cells and tested its antigenicity by ELISA. Rabbits were immunized by the DNA prime-protein boost regimen with a gp120 DNA (ZM109 sequence) and the V1V2 ZM53 -2J9C immunogen. The immunogenicity was then assessed by antibody competition assays. Results: We found that the V1V2-2J9C immunogen could bind mAb PG9, CH58 and 697-D, thus it harbors the V2q, V2p and V2i epitopes. We also found that this immunogen is highly immunogenic in rabbits. Direct binding competition ELISA assays showed strong competition between immune rabbit sera and CH58 or PG9, but not with 697-D, thus this trimeric V1V2 immunogen induced strong antibody responses targeted not only the linear V2p epitope type but also the quaternary V2q epitope type. Conclusions: Our results demonstrate that structurally con- strained V1V2 scaffolds with Env quaternary conformation can be designed and synthesized, resulting in elicitation of antibody responses with specificities overlapping the PG9 epitope region - a first step in immunogen design to target a major vulnerable site of HIV-1 Env. P10.14 LB Chimeric Bovine-V-region and Human-C-region mAbs with Long and Extensively Mutated CDHR3 Domains Bind HIV-1 Env gp140 Trimers, but Not gp120 Monomer Behnaz Heydarchi 1 , Robert Center 1 , Sri Ramarathinam 2 , Christopher Gonelli 1 , Brian Muller 1,3 , Charlene Mackenzie 1 , Jack Cuthbertson 1 , Marit Kramski 1 , Damian F.J. Purcell 1 A121