Researchers take an important step toward an HIV vaccine – University of Copenhagen

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25 April 2017

Researchers take an important step toward an HIV vaccine

Vaccines

Researchers from the University of Copenhagen have developed a strategy that can revolutionise vaccine design. The new strategy is used to develop vaccines that can prevent HIV infection and the development of AIDS.

Vaccines are an essential tool for preventing and treating serious infectious diseases such as polio, chicken pox and measles. But so far it has not been possible to develop vaccines capable of contributing to the treatment and prevention of chronic infectious diseases such as HIV and hepatitis C.

New research from the Faculty of Health and Medical Sciences at the University of Copenhagen paves the way for vaccines that, as opposed to conventional methods, boosting the parts of the immune system attacking the viral genes, which are the least active during the infection. This prolongs the resistance of the immune system to the virus.

Traditional vaccines typically cause a strong stimulation of the parts of the immune system, that are most responsive to the specific virus. But the reaction to the vaccine and the infection is often so intense that the immune system “loses momentum” and consequently is not able to completely eliminate the virus. Researchers have therefore designed a vaccine which boosts the cells of the immune system responsible for the less exposed parts of the virus. As a result, the cells are able to distribute the ‘work load’ and retain the defence against the virus attack for a longer period of time. This gives the immune system time to build a more efficient defence, which may then defeat the remaining of the virus.

“We’re presenting an entirely new vaccine solution. Our vaccine supports the work of the immune system in developing an effective combating mechanism against the virus, rather than immediately combating the toughest parts of the virus. In combination with other vaccines, this approach can prove to have a highly efficient effect,” says Research Team Leader and Associate Professor Peter Holst of the Department of Immunology and Microbiology.

Experiments with monkeys can lead to effective vaccine

In 2008, the research team decided to develop a new vaccine strategy, which generates so-called strong immune responses against weak immunostimulatory parts of viruses. Research initially focused on experiments on mice and later on monkeys.

Now, the results of the research team show, that this technology can control the SIV virus infection (simian immunodefiency virus) in monkeys. SIV is a chronic infectious disease and a highly realistic representation of HIV. The results are an important step toward developing a vaccine against HIV and other chronic infections.

“The next phase of our work is to build virus control in all infected animals and later in humans. We’re convinced that it’s possible to identify further improvements in our experiments and thus achieve a well-functioning vaccine, initially against HIV, but also against other chronic infections," says Peter Holst.

The study “Mucosal vaccination with heterologous viral vectored vaccine targeting subdominant SIV accessory antigens strongly inhibits early viral replication” was published in the scientific journal EbioMedicine. The study is supported by the Danish AIDS Foundation and the Danish Council for Independent Research. The concept is a further development of previous studies of chronic infections in mice, originally carried out in collaboration with Professors Jan Pravsgaard and Allan Randrup from the University of Copenhagen.

Click on image for larger model. 

Text on figure:

The vaccine boosts the immune system's division of work
Prior to the vaccination, the body has only a few cells capable of recognising the HIV virus. 

Top tier: Virus attack without vaccine. When the HIV virus infects the unvaccinated host, the immune system is mainly presented with the strong antigens. The immune cells consequently divide, so that a predominant number of cells can recognise the strong immunostimulatory genes (shown in green). However, the HIV virus division takes place so quickly, that the immune cells cannot keep up in the long run. The weak immunostimulatory genes (shown in pink) only activate the immune system to a mild extent.

Middle tier: Virus attack with traditional vaccine: A vaccination with strong immunostimulatory cells primes the immune system, but the HIV virus will still be able to wear out the immune cells or avoid them through mutation.

Bottom tier: Virus attack with new vaccine strategy: A vaccination with weak immunostimulatory cells boosts the immune system against these genes and also allows an immune system against strong immunostimulatory genes. The result is that the immune system recognises all parts of the virus and divide the work between the strong and weak immunostimulatory genes. The vaccine thus creates a division of work ensuring that the immune system can keep up and combat the virus or in some cases eradicate the infection. 

Fact box on SIV and HIV
Simian immunodeficiency virus (SIV) is found in more than 30 African primate species. It is believed that SIV originally migrated from chimpanzees to humans, among others, where it developed into HIV. This connection renders SIV the most suitable model for studying the immune system's response to an infection.