Adenovirus 26 looks like it could be a safe, new HIV vaccine vector said Dr Dan Barouch from Boston, US, this afternoon at AIDS Vaccine 2009.
The Ad5 virus, which has been tested as a vector (an altered virus to transport the vaccine into the body) in large human clinical trials, initially appeared to have some complications that will not apply to Ad26.
The adenovirus is a common virus that causes colds.
Dr Dan Barouch from Boston said: “One of the main problems with Ad5 is that there is a high pre-existing immunity in the population (many people have been exposed and their immune responses altered). Ad26 is rarely found naturally and so we hope it will be useful.”
Speaking to journalists Barouch, from Beth Israel Deaconess Medical Center, said: “It has a very different interaction on the immune system to Ad5 in triggering an immune response.”
He said: “We showed it gave substantial protection against HIV last year. Now, in a Phase I human study among 36 volunteer and placebo participants, who were given three different doses, it was safe and immunogenic.”
Barouch said the Ad26 vector induced cellular and humoral (antibody) immune responses.
When the results of the STEP Merck Ad5 HIV-1 trial were first released in 2007, there was an initial concern that uncircumcised men who had Ad5 immunity, could be at slightly raised risk of infection.
But further analyses of these results, and its companion Phambili study in South Africa, released at the conference this week found there was no raised risk.
Dr Glenda Gray, director of the Wits Perinatal HIV Research Unit, today presented an “interim efficacy” analysis of data collected in the South African Phambili HIV Vaccine study.
This human clinical trial was halted in September 2007 due to futility (not showing efficacy) found in its companion study known as the STEP study. Both these trials were set up to test the same vaccine, the Merck Adenovirus 5, in uninfected adults.
Concern was raised at the time that uncircumcised men, who had pre-existing immunity to the Adenovirus 5, could be at slightly raised risk. But subsequent analysis of the STEP and Phambili data and follow up presented today showed that this was not in fact associated with increased risk of being infected. In the Phambili trial less than 20% of the participants had no pre-existing immunity to Ad5.
The trial was run in five provinces in South Africa with sites in Gauteng, North West, KwaZulu-Natal and the Western Cape and patients were followed up after September 2007 (data was frozen in August 2009).
Among the major findings that Gray presented were:
*This vaccine did not protect against HIV and there were no difference in new infections between the vaccine and placebo groups by the time of the first vaccination;
*But good cross clade immune reactivity was demonstrated: the vaccine being tested was a sub-type B candidate in an area where sub-type C is most common, but this finding shows at four weeks after two injections most volunteers had developed an immune response to both clades B and C (for clade C the response rate was 77%);
*A reduction in HIV viral load among the women who received the vaccine: 0.57 log reduction in viral load at the set-point (measured at the start of the study);
*early differences in CD4 decline between the vaccine and placebo participants: CD4 counts indicate immune strength so a slower decline is advantageous and over 12 months the vaccine group experienced this benefit but it was not sustained over time;
*Risk reduction behaviour was sustained over time; and
*Good uptake of male circumcision post-enrolment of about 32%: medical male circumcision reduces the risk of a man acquiring HIV by about 60% many studies have proved.
The new HIV infection rate that Gray reported was roughly 4% – about 10 to 20 times higher than the infection rate in the Thailand trial which was conducted among a low-risk population.
The number of vaccinations received did not impact on the probability of acquiring HIV (no statistical difference was found). During the trial 60 volunteers were infected – 40 of them were women.
Two-thirds of the volunteers got two vaccinations and a quarter got only one shot before the trial was suspended.
An update on clinical trials in the first plenary session at AIDS Vaccine 2009 today showed that more effective HIV vaccines are in the pipeline than any that have been tested before.
Gary Nabel, director of the Vaccine Research Centre at the US National Institute of Allergy and Infectious Diseases, said: “We have exciting new candidates that are eliciting response that have not been seen before.”
He told the packed hall that the HIV Vaccine Trials Network is currently testing a product that has shown great promise immunologically – in the lab delivering a “robust” response in stimulating CD4 cells and antibodies.
The HVTN 505 trial is testing a multiclade (includes different sub-types of HIV) DNA vaccine with an Adno booster (intended to stimulate the immune system). This Phase II trial started this year and will wrap up in 2012.
He also described new concepts around T-cell vectors (vaccines that stimulate cell-mediated immune response) and said this field was making advances. In particular he reported on the efficacy of the LCMV (a type of virus) at stimulating a powerful immune response in lab tests and he talked about a new generation of vaccines using the “mosaic” concept.
“On the T-cell side we can look forward to a lot of improvements,” he indicated.
Nabel said progress has been made on stimulating antibody immunity, guided by the analyses of blood from people who successfully generate broad neutralising antibodies.
“These individuals can serve as a guide to vaccine development,” he said.
Nabel emphasised the need to find new ways to measure immunity that will correlate (show a link to) protection against HIV and the important the window of opportunity to stop HIV as soon as it infects the cervix.