IAVI is advancing a distinct portfolio of preventive HIV vaccine candidates through its research and development programs, taking two primary approaches to design candidates: blocking HIV infection by engaging the antibody response or destroying infected cells via cell mediated immunity (CMI). Current CMI-based approaches include the development of replicating vectors and prime-boost strategies.
Adenoviruses, used as vaccine vectors, have been shown to induce strong immune responses by the body’s immune system. IAVI and its partners selected the Adenovirus 35 subtype for development because there are relatively few preexisting immune responses against this virus in the countries that are hardest hit by HIV. Preliminary clinical data from a Phase I trial of an Ad35-based vaccine candidate shows that it was safe, well-tolerated and immunogenic in the study population in which it was tested. The candidate Ad35 vector technology is licensed from Crucell, NV, and the candidate is manufactured by Transgene, SA. The trial was conducted in collaboration with the University of Rochester Medical Center.
Ad35 + Ad26
IAVI and its partners are currently evaluating the safety and immunogenicity of a prime-boost combination of two candidates based on the Ad35 and Ad26 vectors in a Phase I trial. This prime-boost regimen might be able to induce different types or stronger immune responses. The Ad26-based candidate is manufactured by Crucell and was developed at the Beth Israel Deaconess Medical Center, while the Ad35 candidate was developed at IAVI and manufactured by Transgene. The trial is conducted in partnership with National Institute of Allergy and Infectious Diseases, Brigham and Women’s Hospital, the Kenya AIDS Vaccine Initiative, Projet San Francisco, and the HIV Vaccine Trials Network.
Ad35 + Protein
A multicenter, Phase I clinical trial is underway in Africa testing a combination of IAVI’s Ad35 HIV vaccine candidate manufactured by Transgene and a protein-based vaccine component developed and manufactured by GlaxoSmithKline. Previous Phase I studies of the components found that each has an acceptable safety profile, is generally well-tolerated and elicits strong immune responses in humans. The trial is conducted in partnership with the Kenya AIDS Vaccine Initiative, the Uganda Virus Research Institute-IAVI, the Medical Research Council-Uganda Virus Research Institute and the Zambia Emory HIV Research Project..
The candidate is a combination of two components. The first, supplied by Profectus, is a DNA that has been engineered to encode multiple HIV proteins. It is co-delivered with GENEVAX™ IL-12 DNA, which should enhance the immune response to HIV. The second component is based on the Ad35 vector. The candidate is currently being evaluated in a multi-center, Phase I trial in Africa–the first to test this particular combination of vaccine components in humans. The DNA components of the candidate will be delivered using Ichor Medical Systems’ proprietary TriGrid™ Delivery System. The trial is conducted in partnership with Projet San Francisco, Uganda Virus Research Institute and Kenya AIDS Vaccine Initiative.
The Sendai replicating virus vector-based HIV vaccine candidate has advanced to the clinical stage of development. Sendai has been shown to target the gut–the primary site where HIV spreads following infection. The candidate is being developed in partnership with DNAVEC, a Japanese biotechnology company.
Another antibody-based approach for HIV vaccine design is to deliver broadly neutralizing antibodies to HIV in a vector that will produce it in sufficiently large quantity. Researchers at IAVI and the Children’s Hospital of Philadelphia are refining candidates that utilize the Adeno-Associated Virus (AAV) subtype 1 vector to deliver genes into the body to provide long-term expression of PG9, a broadly neutralizing antibody to HIV that IAVI and affiliated researchers identified in 2009.
The canine distemper virus (CDV) is being used as a candidate replicating viral vector for an HIV vaccine because it targets the gut, where HIV initially amplifies and spreads. This could stimulate strong immune responses to control HIV before is spreads to the rest of the body.
HIV ENV Immunogen
Antibodies are large protein molecules that bind unique parts of disease-causing organisms and mark them for destruction. By developing immunogens (the active ingredients of vaccines) based on the parts of the virus to which the antibodies bind, researchers can prompt the body to create protective antibody responses to the targeted virus. But because HIV mutates so rapidly, researchers have not been able to devise an immunogen that covers the stunning variety of HIV circulating worldwide.
Current approaches to designing immunogens include:
- Utilizing cutting-edge technologies to identify broadly neutralizing antibodies in people and determine where on the surface of HIV they bind to identify potential vaccine targets
- Recreating and stabilizing unique versions of the protein spike, or trimer, on the surface of HIV
|Ad35 + Ad26|
|Ad35 + Protein|
|HIV Env Immunogen|