CROI 2015 Program and Abstracts

Abstract Listing

Oral Abstracts

Conclusions: In very late cART era, in a prevalent MSM population, HAND prevalence was close to 50% only in patients selected to NPA for a cognitive complaint. In people with no specific cognitive complaints, prevalence of HAND was confirmed as lower than previously detected, estimated as less than 10% in the more recent years. Higher CD4 count at NPA, higher CD4 nadir, a shorter time from HIV diagnosis and higher educational level were associated to a lower risk of NCI. Receiving a NRTI-sparing ART at cognitive assessment seems to be related to a lower risk of impaired cognition.

Session S-1 Symposium

Room 6C

4:00 pm– 6:00 pm Harnessing Antibodies for Prevention and Therapeutics 64 Potentiating Protective Antibody Activity: A Systems Serology Approach Margaret E. Ackerman Thayer School of Engineering, Dartmouth College, Hanover, NH, US

Antibodies act as a nexus between innate and adaptive immunity: they provide a means to engage a spectrum of innate immune effector cells in order to clear viral particles and infected cells. This functional landscape is remarkably complex, as the humoral response is highly polyclonal, with multiple antibody variants directed to multiple epitopes on multiple viral antigens, and diversity of viral recognition characteristics is further complemented by diversity in ability to recruit the potent anti-viral effector functions of a suite of innate immune effector cells. In vivo, even neutralizing antibodies rely on this ability to act as molecular beacons for innate immunity in order to provide protection, and results from both human and macaque studies have implicated these effector functions in vaccine-mediated protection. We demonstrate a high-throughput, high-content platform for the biophysical and functional interrogation of the innate immune recruiting capacity of polyclonal HIV-specific antibodies capable of parsing this complex humoral milieu into components that can be used to develop computational models of antibody activity and provide insights into mechanisms of vaccination. 65 Impact of Repetitive Protein Boosting on RV305 HIV-1 Vaccine-Induced Antibodies Georgia D. Tomaras Duke University Medical Center, Durham, NC, US Of the six HIV-1 vaccine efficacy trials to date, only one trial, RV144, demonstrated decreased transmission versus the placebo group, with an estimated vaccine efficacy of 60% and 31% at 12 and 42 months, respectively. Antibodies that significantly correlated with HIV-1 infection risk included IgG (in particular IgG3) non-broadly neutralizing antibodies (non-bnAbs) to the V1/V2 region of HIV-1 envelope glycoprotein. Although not broadly neutralizing, these antibodies could mediate antibody Fc-mediated antiviral functions, such as antibody dependent cellular cytotoxicity (ADCC). A unique feature of the RV144 vaccine regimen was the inclusion of a protein boost that was antigenic for both linear strain-specific V2 antibodies, as well as for conformational V1V2-glycan epitopes bound by broad neutralizing antibodies (bnAbs). A subset of RV144 vaccinees were boosted, after a 6-8 year interval, as part of the RV305 vaccine trial. This repetitive boosting with the vaccine immunogen both expanded a pool of antibodies with many of the characteristics of V1V2 bnAbs and, as well, skewed the plasma IgG subclass profile associated with non-bnAbs. New technologies have allowed a deeper interrogation of the B cell repertoire post vaccination and provide insights on the quest to induce broadly neutralizing antibodies and / or further drive non-bnAbs with Fc-mediated antiviral functions. Coauthors: M. Anthony Moody 1 , David Easterhoff 1 , LaTonya Williams 1 , Kevin Saunders 1 , Nicole Yates 1 , Nicos Karasavvas 4 , Sheetal Sawant 1 , Nathan Vandergrift 1 , Judith Lucas 1 , Robert Howington 1 , Jerome Kim 2 , Nelson Michael 2 , Merlin Robb 2 , Robert O’Connell 4 , Sandhya Vasan 4 , Jean-Louis Excler 2 , Supachai Rerks-Ngarm 3 , Punnee Pitisuttithum, Sorachai Nitayaphan 4 , Thomas Kepler 5 , Munir Alam 1 , Guido Ferrari 1 , David Montefiori 1 , Hua-Xin Liao 1 , and Barton Haynes 1 1 Duke Human Vaccine Institute, Duke University, Durham, NC 27710 ; 2 MHRP; 3 Thai Ministry of Health; 4 AFRIMS; 5 Boston University

Oral Abstracts

66 Immunoprophylaxis by Gene Transfer: Shortcut to an HIV Vaccine Phil Johnson Children’s Hospital of Philadelphia, Philiadlphia, PA, US

The holy grail of HIV vaccine development is an immunogen that elicits antibodies which neutralize field strains of HIV frommultiple clades. However, little progress has been made in generating such vaccine candidates, and near-term prospects remain uncertain. In the meantime, we have taken a different approach to HIV immunoprophylaxis that completely bypasses the adaptive immune response. The concept is straightforward. One selects an antibody (or antibody-like molecule) with the desired neutralizing properties, clones the respective gene, and then inserts it into a recombinant adeno-associated virus (rAAV) vector. When injected (intramuscularly) into a host, the vector directs in vivo production of the antibody that leads to serum neutralizing activity against HIV. In other words, antibodies are produced by myofibers instead of plasma cells. We adapted this

121

CROI 2015