In autumn 2011 the Norwegian biotechnology company Bionor Pharma reported promising findings from one of its studies: HIV patients who received the firm’s vaccine Vacc-4x, were twice as likely to not need any medications for at least a year.
Administering HIV vaccines nasally would be simpler and probably cheaper. (Illustrative photo: Dag Kvale) “Vaccination by injection requires good needle technique and lots of practice; otherwise the vaccine never reaches the immune cells,” explains Dag Kvale.
In trials so far, the Vacc-4x vaccine has been administered by injection into the outermost skin layer. Now a slightly modified version of the vaccine will be tested in a research project conducted at Oslo University Hospital.
“Now we will test whether efficacy is just as good when the vaccine is given in nasal-drop form.”
“We have a very different type of immune response in our mucous membranes compared to the skin, so the results may be anything from no effect to somewhat different to better than those obtained by Bionor Pharma so far.”
Professor Kvale, who conducts research at Oslo University Hospital’s Department of Infectious Diseases, makes it clear that his team has several years to go before they can have any definite answer as to whether the nasal vaccine will work.
High potential impact for developing countries
If testing shows that a simple nasal immunisation is effective, it could have a worldwide impact on the treatment of HIV-positive patients. The nasal procedure is simple and low-cost, which are highly significant factors if vaccines are to be administered large-scale and in poor countries with underdeveloped health care systems.
The first clinical trial of a nasal vaccine will be carried out by the end of 2011. The vaccine substance Vacc-4x will be mixed with an adjuvant developed by the Swedish company Eurocine Vaccines. Adjuvants are immunological agents added to vaccines to stimulate the body’s immune response by triggering a mild inflammatory reaction.
In the trial, 18 patients will receive Vacc-4x in various doses mixed with the adjuvant, while a control group of six patients will receive only the adjuvant. The first objective is to find out whether the vaccine administered nasally has any effect on the immune system, and if so, which dosage is best.
The project receives funding under the Research Council of Norway’s Programme for Global Health and Vaccination Research (GLOBVAC).
To strengthen the immune system
The overall objective of the research being carried out by Bionor Pharma and Pofessor Kvale’s group is to develop a therapeutic vaccine that boosts the body’s immune response to the HIV virus, reducing the viral load (the amount of active HIV in an infected person’s blood).
“Only a small proportion of the world’s HIV-positive people have access to treatment,” points out Birger Sørensen, Bionor Pharma’s head of vaccine development. “Our hope is that a therapeutic vaccine will be an effective treatment for HIV patients here in the Western world and in the rest of the world as well.”
Bionor Pharma has collaborated with Professor Kvale’s research group on two previous studies of Vacc-4x, with funding under the GLOBVAC programme. Mr Sørensen believes the results so far make Vacc-4x a frontrunner among HIV vaccine candidates.
“If the coming studies are also successful,” says Mr Sørensen, “we hope the vaccine will be on the market within a few years.”
From HIV to immune-system collapse and AIDS
Professor Kvale’s research group is also investigating what causes HIV infection to develop over time into immune-system collapse and AIDS. Such knowledge could help increase vaccine efficacy.
Vaccine trials to date have merely managed to lower the amount of HIV virus but not provided full control over it. The degree of control and pace at which the virus leads to deteriorating health can vary widely from patient to patient.
Harmful intestinal leakage
Professor Kvale believes that disease mechanisms in the intestine are linked to disease progression. Researchers have observed that in HIV patients there is less control over what kinds of substances can leak out of the intestine into the blood, including substances from intestinal microbes.
Some of the substances from dead, decomposing microbes trigger powerful inflammatory processes which over time overload the immune system and probably accelerate the onset of AIDS.
In collaboration with the Biotechnology Centre of Oslo and Rikshospitalet University Hospital, Professor Kvale and his team have seen that common anti-inflammatory medicines called COX inhibitors can slow the inflammatory processes associated with HIV.
“COX inhibitors may be suitable for HIV patients with limited access to expensive HIV treatment, or who react poorly to such treatment,” says Professor Kvale. “They may also be a means of improving the efficacy of vaccines.”
A particularly challenging virus
Despite the promising results from recent research on therapeutic vaccines, development of a preventive vaccine is still far into the future. It has proven very difficult to figure out how to prevent the HIV virus from entering the body.
One explanation for this is that scientists had relatively little previous experience with retroviruses, particularly when it comes to developing vaccines against them.
Furthermore, the HIV virus has a unique ability to make itself virtually undetectable once inside a cell. The virus can also mutate quickly, making it difficult for the immune system to identify the new variants.
Testing new preventive vaccines is a costly and extensive endeavour – and ethically problematic, according to Professor Kvale. Standard procedure is testing on persons without HIV in parts of the world with extremely high rates of infection.
Thousands of people need to be vaccinated. To find out quickly whether the vaccine actually works, however, researchers have to track infection rates among the many subjects who receive a placebo, and compare these to the rates among subjects who receive the real vaccine.
Perhaps a more ethical alternative would be to test the preventive vaccine as a therapeutic vaccine first – since scientists believe that many of the characteristics that a therapeutic vaccine needs would also be valuable in a preventive vaccine.
“Testing the candidate preventive vaccines in a therapeutic role on HIV-positive subjects would indicate far more quickly whether a candidate is likely to succeed as a preventive vaccine – and would be far less problematic ethically,” concludes Professor Kvale.