VIRxSYS is developing an HIV vaccine (VRX1273) which has shown very promising results in mice and monkey studies. Based on these results, we believe this product may be suitable as a therapeutic as well as a prophylactic treatment for HIV.
VRX1273 is based on the same lentivirus that is, in fact, HIV. VIRxSYS believes that using the lentivirus against HIV gives its vaccine candidate an advantage over other HIV vaccine candidates currently under development.
Although there is no known cure for HIV, many experts have described what would be considered a "functional cure" for HIV. In this context, a functional cure would be a therapy which would lower a patient’s level of HIV to a point where the patient's own immune system could keep the virus in check, even after the therapy is discontinued. According to this concept, a potent intervention would dramatically decrease, but not necessarily fully eradicate HIV replication, would protect the patient's immune system, and would extend life expectancy. Such a therapy would allow HIV infected patients to live long healthy lives, taking less drugs with toxic side effects, allowing better compliance, and could potentially reduce risks of transmission to sexual partners. This concept of a “functional cure” is what VIRxSYS believes is possible with its lentiviral-based vaccine candidate against HIV.
Before describing in greater detail the VRX1273 HIV vaccine program, it would be useful to provide some background in HIV/AIDS itself:
Facts About HIV/AIDS
According to the Joint United Nations Program on HIV/AIDS (“UNAIDS”) [1], an estimated 27 million people have died from HIV/AIDS, with approximately 1.8 million additional deaths this past year. Further, it is estimated that there are more than 33 million adults and children currently infected with HIV, a 27% increase since 1999, with possibly as many as 2.1 million additional people that have been infected each year.
One does not die due directly to HIV infection. Rather HIV kills CD4 T lymphocytes, the “quarterback” of the immune system, which causes a greatly compromised and depleted immune system. As a result, there is an insufficient immune response to defeat any other pathogens causing conditions such as pneumonia, cancers, etc, which ultimately causes the death of the HIV infected patient.
Antiretroviral drug combination therapies (ARVs) are currently the standard treatment used to combat HIV. Generally they are safe and effective at suppressing HIV replication and opportunistic infections in the short-term, but they do not prevent HIV infection and do not reverse HIV infection. If one stops use of ARVs, HIV replication and infection rebounds. In addition, ARVs often cause unwanted side-effects due to the toxic nature of these substances, and lifelong treatment with ARVs can significantly affect a patient's quality of life. More recent data stress the serious long-term side effects of taking ARVs. Finally, HIV is amazingly efficient in mutating. Over time, HIV can become resistant to virtually all forms of traditional ARV treatments on the market today.
Description of VRX1273
VRX1273 is an HIV-based lentiviral vector which has been highly engineered for safety and efficacy. VRX1273 contains none of the HIV disease causing genes, which have been replaced with three HIV antigens in order to mount robust immune responses against HIV [2, 3]. VRX1273 is intended to be injected sub-cutaneously (under the skin), and this administration may potentially be repeated several times in the event boosters are required to sustain a therapeutic effect.
VRX1273 Animal Studies
VIRxSYS has performed extensive preclinical work in mice and monkeys with its HIV vaccine. Following several years of studies of the VIRxSYS vaccine in mice and monkeys, the Company is very optimistic about the vaccine results seen.
Mouse Studies: VIRxSYS first demonstrated in mice that its vaccine candidate VRX1273 could stimulate a significantly greater HIV immune response compared to the previous "gold-standard" in the HIV vaccine field, represented by adenovirus (common cold) vectors. The R&D analog of VRX1273 compared favorably to that of adenoviral vector-based vaccines, which generally have been considered to be the top-ranked vector-based systems for eliciting a strong anti-HIV immunity [4]. The Company also has generated an impressive amount of preclinical data demonstrating the unique features of a lentiviral vector as an HIV vaccine candidate. These results are described more fully in three separate peer reviewed journal articles in the journal Vaccine [2, 3 & 4].
Monkey Studies: VIRxSYS HIV vaccine construct VRX1273 has been formulated to battle HIV in humans. The Company constructed a version of the vaccine specifically for monkeys (VRX1116) which is formulated to battle SIV (the simian, or monkey, version of HIV). The monkey study included 10 rhesus macaque monkeys, divided into two groups of five monkeys per group:
- One group received a lentiviral vector (LV) only vaccination.
- The second group received a placebo vaccination.
After 3 repeat vaccinations of all animals over period of months, the Company challenged (i.e. infected) these monkeys with an extremely high dose of the most potent form of SIV available (SIVmac251) to determine the safety of VRX1116 in the monkeys and to assess how well the vaccine was able to control this potent SIV infection. Long term post-challenge follow-up (up to 16 months) revealed very encouraging results in the study to date, in terms of complete to near-complete viral load control and CD4 T lymphocytes maintenance in some vaccinated animals [5], which offers optimism for planned future human studies.
Demonstrating those findings over a long-term follow-up represents a unique characteristic in a field where other vaccines typically exert only a short term effect, if any. These very unique findings have finally translated into a longer survival of vaccinated animals, compared to infected monkeys that were not vaccinated. If these findings can be translated to humans, it would represent a major step towards a successful vaccine for HIV. At the very least, we would hope this will allow HIV-infected patients to live relatively healthily, possibly longer, while reducing the extent of viral replication and its damage to their immune systems.
HIV/AIDS Key Opinion Leaders’ Feedback on VRX1273
VIRxSYS has presented its ongoing findings to scientists, HIV clinicians and Key Opinion Leaders (KOLs) from around the world, including those at the NIH, at conferences such as CROI (Conference on Retroviruses and Opportunistic Infection) in San Francisco in February 2010, the Vienna International AIDS Conference in August 2010, the AIDS Vaccine Conference in Atlanta in September 2010, the 2010 American Public Health Association Meeting in Denver, the HIV DART in Los Cabos, Mexico in December 2010, and to the Company’s globally renowned HIV Medical Advisory Board. The Company has received extremely favorable feedback on the data presented. For example, Dr. Joep Lange, the head of the Amsterdam Institute for Global Health and Development, Professor of Medicine at the Academic Medical Center, University of Amsterdam., President Emeritus of the International AIDS Society, and member of the VIRxSYS medical advisory board for HIV, stated, “Obviously, the HIV vaccine field has been hit with a number of disappointing trial results over the past several years. The results from this trial are very impressive and I believe could provide real excitement in the world of HIV vaccines.” Other HIV and vaccine experts expressed similar views and have encouraged VIRxSYS to move VRX1273 to human clinical trials as quickly as possible.
Next Steps for VRX1273
A Pre-IND meeting for VRX1273 was held with the Food and Drug Administration (FDA) in July 2010. The meeting outcome was very successful in that no major safety or clinical issues were identified at the time, which would prevent VIRxSYS from filing an IND application with the FDA.
VIRxSYS is now finalizing the remaining preclinical studies, as discussed with the FDA, for inclusion into the IND application, and is also preparing for its proposed Phase I human clinical trials for VRX1273.
Because of the devastating human impact that HIV/AIDS has had around the world, a significant number of attempts have been made to develop an HIV vaccine. The vast majority of the HIV vaccine trials to date have been for prophylactic HIV vaccines. While VRX1273 may one day have prophylactic application, VIRxSYS plans to move this product into clinical trials initially as a therapeutic vaccine. There have been numerous efforts to develop a therapeutic vaccine for HIV. VIRxSYS believes that while some of these programs have had some modest success, each of these programs/product candidates has helped move the field forward. However, none of them has resulted in compelling human clinical data so far.
VIRxSYS is very proud of the results to date with its vaccine candidate in monkey studies, including survival advantage and achieving undetectable viral load in some of the vaccinated animals, despite the highly virulent strain and dose of SIV used to challenge the monkeys. Because of this, VIRxSYS believes that VRX1273 has an outstanding opportunity to generate compelling data in humans where all other vaccine candidates have failed to date.
References:
[1] UNAIDS report (http://www.unaids.org/documents/20101123_GlobalReport_em.pdf)
[2] Lemiale et al. An HIV-based lentiviral vector as HIV vaccine candidate: Immunogenic characterization. Vaccine 28(8):1952-61, 2010.
[3] Lemiale & Korokhov. Lentiviral vectors for HIV disease prevention and treatment. Vaccine 27(25-26):3443-9, 2009 (Review)
[4] Asefa et al. Heterologous HIV-based lentiviral/adenoviral vectors immunizations result in enhanced HIV-specific immunity. Vaccine 28(20):3617-24, 2010.
[5] Lemiale F. HIV DART 2010, Los Cabos, Mexico. (http://www.informedhorizons.com/hivdart2010/_pdf/BrochureEmail_HIVDART2010.pdf)