Two types of immune responses can limit or prevent HIV infection in humans and animals.  These include cellular responses by cytotoxic “killer” T-cells (CTLs) and antibody responses by viral neutralizing antibodies (NABs).  While CTLs only kill cells already infected with HIV, NABs prevent infection by blocking HIV viral entry and clearing circulating virus.  Existing HIV vaccine candidates attempt to induce one or both of these immune responses.  However, developing vaccines that induce responses capable of controlling viremia after challenge has proven to be extremely difficult due to the ability of HIV to mutate rapidly and change those fragments of virus used by the vaccine to elicit the immune response.  The Company’s HIV vaccine candidate attempts to solve this problem by targeting the immune response to portions of HIV that cannot tolerate mutations. 

Transition-State Vaccines

Immunogen: The Company is developing a novel HIV Vaccine Immunogen based on its proprietary strategy called Transition-State Vaccines. This strategy targets immune responses to conserved portions of viral spikes. This is accomplished through the use of chimeric fusions between a portion of the viral surface spike and a small binding portion of its cognate receptor via a small amino acid linker. The linker is sufficiently long that the two components will interact to complete an intermolecular bond. Such immunogens redirect the immune response away from highly variable regions of the envelope spike that usually act as immunological decoys to regions that are highly conserved. For HIV, these conserved regions could be the “Achilles heel” for all HIV isolates. These constructs are produced from a single construct, thus allowing production in a variety of mammalian cell systems.  It can also be incorporated into both DNA and vectored vaccines in order to stimulate key cellular responses such as CTLs. 

The Company has entered into an option agreement, with a follow-on license agreement, with Wyeth for the commercialization of this technology for both prophylactic and therapeutic use.

Genetic Adjuvants: To support its vaccine program, the Company has in-licensed an adjuvant technology from UMBI that can be directly encoded into the genetic vaccines, such as DNA vaccines, and can improve their performance.  Genetic vaccine platforms are favored by many vaccine companies because they provide flexibility and uniformity in vaccine construction and production as well as strong IP positions.  However, they do not always induce the desired protection to the target disease or pathogen. To solve this problem, the Company’s Genetic Adjuvant technology uses the enzymatically-active region of cholera toxin (CTA1).  CTA1 can directly activate dendritic cells, the key first responders of the immune system.  By doing so, this adjuvant can facilitate the induction of potent and potentially protective immune reponses to the target pathogen.

Thermal Stabilizers: Development of vaccine formulations that can be transported around the globe will be a key requirement for an HIV vaccine, since populations under the greatest threat from the pandemic are in areas of the world that present significant distribution challenges. Chaperones from thermophilic bacteria may protect live bacterial and subunit vaccines from thermal insults. These Thermal Stabilizers present an opportunity to develop vaccine formulations that could be distributed worldwide without the use of a “cold-chain”, a key advantage for any vaccine. The Company has executed a Cooperative Research Agreement with Dr. Frank Robb at the Center of Marine Biology, UMBI, a preeminent scientist in this arena, to identify suitable proteins from his collection of extremophiles.