October 17th, 2017
New York, NY, October 17, 2017 – The Abzyme Research Foundation (ARF) today announced a new gift to Dr. Sudhir Paul’s Laboratory at The University of Texas Health Science Center at Houston (UTHealth). This gift will provide needed funds to test the ability of a novel HIV vaccine candidate developed by Dr. Paul’s team to prevent HIV’s resistance, which is the ability of the virus to escape neutralization by the immune system. The HIV vaccine candidate, an electrophilically activated variant of the virus coat protein gp120 (HIV E-Vaccine), has been researched by Dr. Paul and his team at McGovern Medical School at UTHealth to determine its effectiveness at inducing robust and long-lasting antibody responses to a structurally conserved region of the gp120 envelope protein – one that if results in clinical trials are similar to studies in the laboratory could hold potential for preventing (prophylaxis) and curing (fully effective therapy) HIV infection.
“It is our hope that the successful completion of this study will mark another milestone achievement by our team and encourage further support for this vaccine from the scientific establishment,” said Dr. Paul, professor in the Department of Pathology and Laboratory Medicine and director of the Chemical Immunology Research Center at McGovern Medical School. “Completely preventing and curing HIV infection hinges on eliminating the development of HIV resistance to the proposed curative agent. We remain hopeful that by further examining our approach to curbing resistance, we can build on previous progress on readying the E-Vaccine for human trials.”
One of the most pervasive challenges to the development of an effective HIV vaccine and potential cure is HIV’s ability to develop resistance to vaccine-induced antibodies. HIV develops resistance upon sustained exposure to all known individual drugs and antibodies that are not directed to the CLIN binding region on human white blood cells [1,2]. The underlying mechanism of HIV resistance is its capability to mutate more rapidly than the host immune system can generate new antibodies directed to the newly emerged epitopes.
Because mutations in the CLIN impair the ability of HIV to infect cells [3], targeting the CLIN may be a powerful means to avoid development of HIV resistance. This is supported by data indicating that antibodies from long-term survivors (LTS) who are able to control HIV infection over decades completely inactivate (neutralize) the infection of host cells by the contemporaneous HIV strains from their own blood. The research being conducted by Dr. Paul and his colleagues will explore whether and how the E-Vaccine can activate a similar protective response and gain new insights into the virus resistance pattern.
“Through this gift to Dr. Paul’s lab at UTHealth, we propose to test the development of HIV resistance to antibodies that recognize the gp120 region targeted by the vaccine. Results from this study will be published in a peer-reviewed journal and presented at an appropriate infectious disease conference,” said Zachary Barnett, founder and executive director of the Abzyme Research Foundation. “Our entire Board of Directors is proud to make this gift of $325,000 to UTHealth, our largest to the university to date, which was made possible by proceeds from our latest Free Me Campaign with Grammy nominated singer Sia as well as the generosity of the Stansbury Family Trust in memory of their son Scott Stansbury.”
About the HIV E-Vaccine:
The electrophilic gp120 vaccine candidate (HIV E-Vaccine) has yielded encouraging information. The HIV E-Vaccine is composed of recombinant gp120 that is chemically activated by insertion of electrophilic phosphonate ester groups. The HIV E-Vaccine protein binds covalently to B cells by an electrophile-nucleophile pairing mechanism, thereby activating a novel immune pathway that induce the synthesis of protective antibodies to CLIN [4]. Conventional vaccines fail to induce the synthesis of such protective antibodies. The HIV E-Vaccine is the only documented vaccine candidate that induces antibodies with ability to neutralize genetically diverse HIV strains across all major HIV subtypes found across the world [4-6].
About Abzyme Research Foundation
ARF is pursuing an HIV cure trial through an innovative non-profit/for-profit model for expediting the development of this unmet medical need. Working with Dr. Sudhir Paul and the biotech company he started, Covalent Bioscience, we believe we can overcome the scientific and societal challenges of developing an effective and low-cost HIV vaccine that is equitably accessible for HIV therapy and prophylaxis worldwide.
ARF and Covalent are dedicated to the development of an effective HIV vaccine, a medical innovation that is desperately needed the world over, most desperately in the developing world where economic conditions often limit access to therapy, much less the most recent advancements in medicine. We are strongly committed to being a leader in not just the development of an HIV vaccine, but also in the creation of sales and distribution practices that allow access to innovations in HIV treatment and prevention to all, not just those that can afford it.
Abzyme Research Foundation Contact
Zachary Barnett
zach@endhiv.com
References
- Waheed AA, Tachedjian G. Why Do We Need New Drug Classes for HIV Treatment and Prevention? Curr Top Med Chem. 2016;16:1343-1349.
- Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S, Mouquet H, Spatz LA, Diskin R, Abadir A, Zang T, Dorner M, Billerbeck E, Labitt RN, Gaebler C, Marcovecchio PM, Incesu RB, Eisenreich TR, Bieniasz PD, Seaman MS, Bjorkman PJ, Ravetch JV, Ploss A, Nussenzweig MC. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature. 2012;492:118-122. PMCID: PMC3809838.
- Planque S, Salas M, Mitsuda Y, Sienczyk M, Escobar MA, Mooney JP, Morris MK, Nishiyama Y, Ghosh D, Kumar A, Gao F, Hanson CV, Paul S. Neutralization of genetically diverse HIV-1 strains by IgA antibodies to the gp120-CD4-binding site from long-term survivors of HIV infection. AIDS. 2010;24:875-884. PMCID: PMC2881561.
- Nishiyama Y, Planque S, Mitsuda Y, Nitti G, Taguchi H, Jin L, Symersky J, Boivin S, Sienczyk M, Salas M, Hanson CV, Paul S. Toward effective HIV vaccination: induction of binary epitope reactive antibodies with broad HIV neutralizing activity. J Biol Chem. 2009;284:30627-30642.
- Planque SA, Mitsuda Y, Nishiyama Y, Karle S, Boivin S, Salas M, Morris MK, Hara M, Liao G, Massey RJ, Hanson CV, Paul S. Antibodies to a superantigenic glycoprotein 120 epitope as the basis for developing an HIV vaccine. J Immunol. 2012;189:5367-5381. PMCID: PMC3755593.
- Planque S, Mitsuda Y, Chitsazzadeh V, Gorantla S, Poluektova L, Nishiyama Y, Ochsenbauer C, Morris M-K, Sapparapu G, Hanson CV, Massey RJ, Paul S. Deficient synthesis of class-switched, HIV neutralizing antibodies to the CD4 binding site and correction by electrophilic gp120 immunogen. AIDS. 2014;28:2201-2211.