BPS 2014
D-Template Assembled Trimeric Peptide Mimetics of the HIV-1 gp41 Pre-Hairpin Intermediate Induce D5-like Neutralizing Antibody Responses
Chengwei Wu
Scientist, Merck Research Laboratories
ABSTRACT
Efforts to develop an HIV-1 vaccine have focused on conserved structural elements that are the target of broadly neutralizing monoclonal antibodies (bnMab). The drug Fuzeon® validates the pre-hairpin intermediate (PHI) as an effective therapeutic target in humans. Mab D5, which binds to a highly conserved hydrophobic pocket on the N-Heptad Repeat (NHR) coiled-coil, demonstrates that antibodies directed against the pre-hairpin can be neutralizing. Proceeding from knowledge of the crystal structure of D5 bound to its epitope, peptide immunogens, displayed as highly structured coiled-coil trimers, have evolved from presentation of the minimal epitope sequence (N17) to extended sequences encompassing larger portions of the NHR (N36). Direct comparison of covalently constrained N17 and N36 trimers in rodent immunogenicity studies showed that the longer peptide elicited higher titers of functional neutralizing antibodies, suggesting that neutralizing epitopes outside of the D5 pocket may exist.
Herein, we present work focuses on efforts to further extend coverage of the gp41 NHR region by engineering and testing 51-residue peptides (N51) in the context of covalently stabilized trimers to determine whether increased neutralization potency is realized in animals vaccinated with these constructs. We report the synthesis of six stabilized trimers in which three copies of N51 are covalently attached to a 3-fold symmetric template. We evaluate the peptides in rodent and primate immunogenicity studies and demonstrate their abilities to elicit high peptide-specific antibody responses which neutralize the D5 hypersensitive V570A virus, as well as other clinical HIV-1 clades. We show antiviral potency results for the trimer based on an in vitro viral entry inhibition assay and confirm the ability of D5 to recognize these structures.
BIO
Information for BPS Presenters
The Boulder Peptide Foundation was established to further the science and knowledge of peptide technology to develop novel therapeutics, biomaterials, medical diagnostics and other beneficial uses for mankind. As part of this goal we run several programs to support career advancement, seminars and educational events. Join us on our mission to expand the applications of peptide science.
Information for BPS Presenters
The purpose of the Boulder Peptide Symposium is to encourage sharing of information related to peptide therapeutic development with an emphasis on the technical, scientific and regulatory aspects of the pharmaceutical development. Presentations that demonstrate original thinking or share experiences from case studies in product development shall receive priority over others.
The Boulder Peptide Symposium offers multiple opportunities for participants to present.
Oral Presentations in Scientific Sessions
The session topics for Scientific Program are Peptides in the Clinic, Drug Delivery, Chemistry of Complex Peptides, Spotlight on Discovery, and Peptide Showcase. Abstracts may be submitted via the Apply to Present page on the website. Submissions will be reviewed by the Scientific Advisory Board on a monthly basis and the speaker will be notified of a decision.
Presentation length: Format is 25-30 minutes slide presentation with 5-10 minutes for Q&A, with the exception of Peptide Showcase talks which are 10 minute slide presentations with 5 minutes for Q&A. Please confirm with your session chair to confirm the exact presentation length.
Invited Speakers: Speakers are requested to supply their presentation details 30 days after receiving an invitation to present.
Program Book Deadline: Final abstract and title must be provided no later than September 1st. No changes to the program are possible after this date.
Presentation Format: Oral presenters please provide your presentation slides to the A/V table on the day of your presentation.
Lodging: All speakers are requested to reserve their own room. Discount rates at the conference hotel are available until August 16th.
Registration: All speakers, excluding sponsored presentation speakers, receive a complimentary registration upon approval of the abstract.
Peptide Showcase Description
The Peptide Showcase is an opportunity for an individual or company to “showcase” new ideas, technology and pipeline assets. Priority shall be given to presentations from biotech and startup companies. Service providers and vendors are not eligible. Speakers in the session receive a complimentary event registration.
Posters
Posters can be presented on any topic relevant to peptides including original research, innovative products and technologies.
Eligibility- Any attendee (from academia, industry, biotech or vendor/sponsor) can present a poster. The presentation must contain original scientific thinking. To submit a poster go to the Submit a Poster link from the meeting menu. All submissions are reviewed on a rolling basis and will be notified of approval. September 1st is the last day to submit a poster abstract. Approved posters are published on the BPF website.
A 30 ” x 40″ board shall be provided with thumb tacks. Board will be on an easel and can be rotated for either landscape or portrait formats. Once you apply for a poster, you will get email confirmation that your poster was accepted. The poster session and number assignments will be emailed one week before the Symposium.
Poster boards shall be available for display from 8am to 8pm the day of your assigned poster session. See the program agenda for the poster session schedule.
Public Release
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