SAV001-H is the first candidate preventive
HIV vaccine
An HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals.
It is thought that an HIV ...
using a killed or "dead" version of the
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
virus.
The vaccine was developed by Dr. Chil-Yong Kang and his research team at Western University’s
Schulich School of Medicine & Dentistry
The Schulich School of Medicine & Dentistry is the combined medical school and dental school of the University of Western Ontario, one of 17 medical schools in Canada and one of six in Ontario.
History
The medical school at the University of ...
in Canada.
The results of the Phase I clinical trial, completed in August 2013, showed no serious adverse effects in 33 participants.
Vaccine design
![Various approaches for HIV vaccine development](https://upload.wikimedia.org/wikipedia/commons/7/78/Various_approaches_for_HIV_vaccine_development.jpg)
The SAV001-H vaccine is considered to be the first whole killed genetically modified
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
vaccine.
According to Dr. Kang, the
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
strain was genetically engineered such that first, “the gene responsible for pathogenicity, known as ''nef''” is removed to make it non-pathogenic. Then, the signal peptide gene is replaced with a honey bee toxin (
melittin
Melittin is the main component (40–60% of the dry weight) and the major pain producing substance of honeybee (''Apis mellifera'') venom. Melittin is a basic peptide consisting of 26 amino acids.
Function
The principal function of melittin a ...
) signal peptide to make the virus production much higher and faster. In the signal peptide exchange process, another gene called ''vpu'' is lost due to an overlapping. Finally, this genetically modified version of
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
, (i.e.,
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
virus with ''nef'' negative, ''vpu'' negative and signal peptide gene replaced with those of a honey bee) is grown in human
T-lymphocytes
A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...
(A3.01 cell line), collected, purified and inactivated by AT-2 (aldrithiol-2 or
2,2'-Dipyridyldisulfide) chemical treatment and gamma irradiation. AT-2 chemical treatment is used because it does not affect the viral structure and immunogens.
The killed virus vaccine approach successfully prevents polio, influenza, cholera, mumps, rabies, typhoid fever and hepatitis A. At the moment, there are also 16 animal vaccines using the killed virus design. A vaccine against
feline immunodeficiency virus
Feline immunodeficiency virus (FIV) is a ''Lentivirus'' that affects cats worldwide, with 2.5% to 4.4% of felines being infected.
FIV was first isolated in 1986, by Niels C Pedersen and Janet K. Yamamoto at the UC Davis School of Veterinary M ...
(a virus related to HIV which infects cats) used the kills virus design - the vaccine was discontinued from production for multiple reasons, including commercial non-viability, protection not covering all FIV strains, and concerns over sarcoma at the injection site caused by adjuvants.
Clinical trials
Phase I clinical trial (NCT01546818) in HIV-infected individuals
Funded by Sumagen Canada, the government of Canada and the Bill and Melinda Gates Foundation, it started in March 2012 to assess its safety, tolerability, and immune responses. This was a randomized, double-blind, placebo-controlled trial, administering vaccine intramuscularly to 33 chronic
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
infected individuals being treated with
HAART
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multip ...
.
The trial was completed in August 2013. It reported no serious adverse effects. The vaccine induced antibodies in participants. Antibodies against
gp120
Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from ...
surface antigen and P24 capsid antigen increased up to 6-fold and 64-fold, respectively, and the increased level of antibody was continued throughout the 52-week study period. Broadly neutralizing antibodies were found in some blood samples of the participants.
Phase II clinical trial
The Phase II clinical trial was expected to begin in 2018 in the United States to measure immune responses. The researchers planned to recruit about 600 HIV-negative volunteers who are in the high risk category for HIV infections such as commercial sex workers, men who have sex with men (MSM), injecting drug users, and people who have unsafe sex with multiple partners.
Therapeutic HIV vaccine status
Dr. Kang has also developed a therapeutic HIV vaccine employing recombinant vesicular stomatitis viruses carrying of HIV-1gag, pol and/or env genes. Researchers reported that the therapeutic vaccine induced robust cellular immune responses in animal tests recently conducted.
History of killed HIV vaccine
Although the whole killed virus vaccine strategy is successfully used worldwide to prevent diseases like polio, influenza, cholera, mumps, rabies, typhoid fever and hepatitis A , it did not receive serious attention in HIV vaccine development, for scientific, economic and technical reasons. First, there are risks associated with inadequately inactivated or not killed HIV remaining in vaccines. Second, massive production of HIV is not economically feasible, if not impossible. Third, many researchers believe that inactivating/killing HIV by chemical treatment also removes its antigenicity, so that it fails to induce both neutralizing antibodies and
cytotoxic T-lymphocyte or
CD8+ T cells
A cytotoxic T cell (also known as TC, cytotoxic T lymphocyte, CTL, T-killer cell, cytolytic T cell, CD8+ T-cell or killer T cell) is a T lymphocyte (a type of white blood cell) that kills cancer cells, cells that are infected by intracellular pa ...
(CTL). Fourth, early studies with monkeys using the killed
simian immunodeficiency virus
''Simian immunodeficiency virus'' (''SIV'') is a species of retrovirus that cause persistent infections in at least 45 species of non-human primates. Based on analysis of strains found in four species of monkeys from Bioko Island, which was iso ...
(SIV) vaccine showed some optimism but it turned out that the protection was attributable to responses to both the cellular proteins on the SIV vaccine and on the challenge virus grown not in monkey cells but in human cells. Fifth, lab-adapted
HIV-1
The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...
seemed to lose envelope glycoprotein,
gp120
Envelope glycoprotein GP120 (or gp120) is a glycoprotein exposed on the surface of the HIV envelope. It was discovered by Professors Tun-Hou Lee and Myron "Max" Essex of the Harvard School of Public Health in 1988. The 120 in its name comes from ...
, during preparation.
Nonetheless, many scientists and researchers believe that the whole killed virus vaccine strategy is a feasible option for an
HIV vaccine
An HIV vaccine is a potential vaccine that could be either a preventive vaccine or a therapeutic vaccine, which means it would either protect individuals from being infected with HIV or treat HIV-infected individuals.
It is thought that an HIV ...
.
Jonas Salk
Jonas Edward Salk (; born Jonas Salk; October 28, 1914June 23, 1995) was an American virologist and medical researcher who developed one of the first successful polio vaccines. He was born in New York City and attended the City College of New ...
had developed a therapeutic whole killed HIV vaccine in 1987, called
Remune, which is being developed by Immune Response BioPharma, Inc., Remune vaccine completed over 25 clinical studies and showed a robust mechanism of action, restoring white blood cell counts in CD4 and CD8 T cells by reducing viral load and increasing immunity.
Developer and organizers
The developer of SAV001-H, Dr. Chil-yong Kang, is a professor of Virology in the Department of Microbiology and Immunology,
Schulich School of Medicine & Dentistry
The Schulich School of Medicine & Dentistry is the combined medical school and dental school of the University of Western Ontario, one of 17 medical schools in Canada and one of six in Ontario.
History
The medical school at the University of ...
at the
University of Western Ontario
The University of Western Ontario (UWO), also known as Western University or Western, is a public research university in London, Ontario, Canada. The main campus is located on of land, surrounded by residential neighbourhoods and the Thames R ...
since 1992. In addition to HIV preventive and therapeutic vaccine candidates, Dr. Kang is developing a second generation vaccine against
hepatitis B
Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. ...
and
hepatitis C virus.
The patents related to the SAV001 vaccine were registered in more than 70 countries, including the U.S., the European Union, China, India, and South Korea.
US Patent: Hiv combination vaccine and prime boost
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References
{{reflist
External links
Clinical Trial Site for SAV001-H
Killed HIV Vaccine Advocate
IAVI Report: Whole Killed AIDS Vaccines
US Patent: HIV COMBINATION VACCINE AND PRIME BOOST
Sumagen Canada Homepage
Curocom Homepage
Schulich School of Medicine & Dentistry
HIV vaccine research